L E AR N I N G O BJ E C T I V E S C HAPTER OUTLI NE

L01 Define mental disorder. What Does It Mean to Biochemistry and

Have a Mental Disorder? Treatment of Bipolar
L02 Analyze the major symptoms and possible Autism Spectrum Disorder
biological correlates of autism spectrum disorder Disorder (ASD) Major Depressive
and attention deficit hyperactivity disorder. Causes of ASD Disorder (MOD)

Brain Structure and Genetic Contributions

L03 Summarize the major biological correlates and Function in ASD to MDD
treatments of schizophrenia. Treatment of ASD Environmental
Attention Deficit
Influences on MDD
L04 Compare and contrast the main features of Hyperactivity Disorder Brain Structure and
bipolar disorder and major depressive disorder. (ADHD) Function in MDD
Biochemistry ofMDD
LOS Differentiate between the major featu res, causal
Causes of ADHD
Brain Structure and Treatment of MDD
factors, and treatments of panic disorder, Function in ADHD Interim Summary 1 6.2
posttraumatic stress disorder, and obsessive­ Treatment of ADHD Anxiety Disorders
compulsive disorder. Interim Summary 1 6 . 1 Obsessive-Compulsive

L06 Describe the biological correlates of antisocial

Schizophrenia Disorder (OCD)

Genetic Contributions Posttraumatic Stress

personality disorder. Disorder (PTSD)
to Schizophrenia
Environmental Brain Structure and
Influences on Activity in PTSD
Schizophrenia Biochemistry and
Brain Structure Treatment of PTSD
and Function in Antisocial Personality
CONNECTING TO RESEARCH: Genetic Overlap in Five
Schizophrenia Disorder (ASPD)
Disorders
The Biochemistry of Genetics and ASPD
BUILDING BETTER HEALTH: The Gut M icrobiota and Schizophrenia Brain Structure and
Mental Disorders Treating Schizophrenia Function in ASPD
BEHAVIORAL NEUROSCIENCE GOES TO WORK: Applied Bipolar Disorder Treatment of ASPD
Behavior Analysis Genetics and Bipolar Interim Summary 1 6. 3
Disorder Chapter Review
THINKING ETHICALLY: Are Psychopaths Responsible for
Brain Structure and
their Behavior?
Function in Bipolar
Disorder

SSS

Copyrip 2019 eeap,e Leamiq. AU ltlpu -.od. May noc bea>pied. .......i or ......- lawtaoleor la p111. Due oo_ .,..._ ...., dlinl ,..,. ...,_ ..ybe--from dle e- llldlor �•�
f.dilOrill review b-. deemed tbM MY .......- coaac does noc maerially lffecl lbe ovenD larniq aperieDce. Cenpae l..anina ruerves the fiPI 10 remove ldditioml Com.I M my lime ir sut.quena ripu raaictioM require iL
556 C H APTER 1 6 Psychopathology

mental disorder A syndrome What Does It Mean to Have a Mental Disorder?

characterized by clinically
significant disturbance in an
individual's cognition, emotion According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5;
regulation, or behavior that American Psychiatric Association [APA), 2013), a mental disorder is "a syndrome
reflects a dysfunction in the characterized by clinically significant disturbance in an individual's cognition, emotion
psychological, biological, or
development processes underlying regulation, or behavior that reflects a dysfunction in the psychological, biological, or
mental functioning. development processes underlying mental functioning" (p. 20).
A course in behavioral neuroscience cannot provide a comprehensive description of
all mental disorders classified by the DSM-5. Instead, our focus will be on disorders that
feature substantial biological correlates, such as genetic vulnerability, structural differ­
ences in the brain, and biochemical differences, that support biologically based treatments.
Throughout this discussion, remember that we have few if any objective assessments that
tell us whether someone has a particular condition. Unlike standard medicine, where a
blood test or x-ray might provide definitive evidence of a disease, mental disorders are
diagnosed through clinical observations of symptoms. As a result, the organization of
the DSM-5 might not reflect the biological causality of disorders. For example, five disor­
ders that occupy different categories in the DSM-5 based on observable symptoms share
overlapping genetic profiles. Schizophrenia, bipolar disorder, depression, attention deficit
hyperactivity disorder, and autism spectrum disorder have more in common than was pre­
viously recognized (Cross-Disorder Group of the Psychiatric Genomies Consortium, 2013).
The National Institute of Mental Health (NIMH) has launched a Research Domain
Criterion project (RDoC) to emphasize the biological and psychosocial bases of disor­
ders instead of observable behavioral symptoms (Insel, 2014). The ultimate goal is pre­
cision psychiatry, or the ability to tailor treatments to specific individuals. In precision
medicine, a drug for cystic fibrosis is effective, but only for the 4 percent of patients
with one out of 1,500 mutations in a single gene associated with the disease. Reaching
this standard of individualized care for mental disorders will require substantial addi­
tional research, but the outcomes for patients will surely justify the effort.
Although we still have much to learn, significant progress in our understanding and
treatment ofmental disorders has occurred over the past six decades. Previously, this area
had not been the most enlightened aspect of human history. With the exception of bright
spots of knowledge in ancient Egypt and Greece, people have typically accounted for
mental disorders with supernatural explanations.
Medieval Europe experienced mass instances of
25 "dance mania;' in which individuals would move
QI
E
in unusual, uncontrollable ways. Their supersti­
:;::; tious neighbors assumed that they were possessed
� • Men
:i 20 • Wo me n
and offered the "cure" of being burned at the stake.
.5 We now suspect that the dancers had Sydenham's
I/)
'iii chorea, which is a rare consequence of strep
0 15
c: infections. As medical knowledge progressed, we
Cl
l1J
i5
gained a greater understanding of the underlying
= 10 biological causes of disorders. However, as recently
'i: as the 1940s and 1950s, parents were blamed for
QI
Cl causing schizophrenia and autism spectrum disor­
.s der. Today, we combine our understanding of the
c: 5
QI
0 interactions between biology and experience to
.....

if explain and treat mental disorders.

0 A scientific understanding of mental disor­
Depression Anxiety Bipolar Schizophrenia ders is urgent, given the large numbers of people
• Figure 16.1 Mental Disorders Are Common Significant num­ affected by these disorders and their costs to soci­
bers of adults in the United States report having been diagnosed with ety. Approximately 26.2 percent of Americans
mental disorders at some time during their lives. Mental disorders over the age of 18 meet DSM criteria for a mental
account for more disability in developed countries than any other disorder in any year, with anxiety disorders and
group of illnesses, including cancer and heart disease (CDC, 201 1 ). mood disorders being the most frequent (Kessler,
Chiu, Demler, & Walters, 2005) (see •Figure 16.1).

Copyright 2019 Cengage Learning. All Rights Reserved. May not b e copied, scanned, o r duplicated, I n whole o r in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChapter(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccngage Learning reserves. the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
 What Does It Mean to Have a Mental Disorder? 557

Connecting to Research
G E N ETIC OVERLAP IN FIVE DISORDERS

P eople can vary from one another genetically i n many

millions and possibly billions of ways. Out of all of
these possible sources of variation, people diagnosed
Of the five disorders, schizophrenia and bipolar dis­
order showed the greatest genetic overlap in heritability,
at 1 5 percent. The overlap between bipolar disorder and
with schizophrenia, bipolar disorder, major depressive depression was 1 0 percent, 9 percent between schizo­
disorder, autism spectrum disorder, or attention defi­ phrenia and depression, and 3 percent between schizo­
cit hyperactivity disorder shared variations in only four phrenia and autism spectrum disorder. Overall, common
genes (Cross-Disorder Group of the Psychiatric Genom­ genetic variations explained 1 7 to 28 percent of the risk
ics Consortium, 201 3). Two of these genes participate in for the disorders, so clearly other factors are i nvolved.
the process of moving calcium into cells, which affects We will explore the possible causes of these and other
the release of neurochemicals at the synapse. psychological disorders in the remainder of this chapter.

Build ing Better

THE G UT M ICRO BI OTA AND MENTAL DI SORDERS
HEALTH
�'"''""''"''''"''"''""''�'"''''"''"'''"'''"'''�'''"''"''"''''"'''"'''"''"''''"''"'''�''�''""''""""''"''""''�''"''"''''"''"''''"''"''''"''"''"''''"'''"'''"''"''''"'''"''"'''"'''""''"''""'�

xciting advances in our understanding of bidi­ Prenatal factors Postnatal factors

rectional interactions between the central ner­
vous system, the enteric nervous system, and the
gastrointestinal tract from animal studies suggest Delivery method
that the gut microbiota might play an important (vaginal vs.
role in some mental disorders (Mayer, Tillisch, & Environment Cesarean)
Gupta, 201 5). The nervous system, and the auto­ (psychologicaV
physical stress)
nomic nervous system in particular, affects the Feeding method
gut microbiota through the release of serotonin, Genetics (breastfeeding
Maternal stress, vs. formula)
norepinephrine, and other neurochemicals in the nutrition, infection,
gut. Microbes in turn release signaling factors disease,
that not only affect local cells in the gut but also medication
Use of pre-/
the brain via the vagus nerve and the circulation probiotic supplements
(Mayer et al., 201 5). and/or antibiotics
Influences of the gut microbiota might be
more significant at certain stages of develop­
ment. Prenatal ly, the fetus is exposed to mater­
nal gut-derived metabol ites and intra-uterine
microbes. The newborn is exposed to different In utero brain Newborn gut
sets of microbiota in vaginal versus caesarean development microbiota
delivery and when breast or bottle fed (see
• Figure 1 6.2). The implications of these differ­ • Figure 16.2 E a rly Influences on the Gut Microbiota The prena­
ences are only beginning to be explored.
tal and newborn phases of brain development might be particula rly
open to influence by the gut microbiota. Prenatally, the mother's own
Animal research showing effects of gut bac­
microbiota, affected by her stress, nutrition, infections, and medica­
teria on anxiety and social behavior has led to
tions, m i g h t influence the brain development of the fetus. After b i rth,
proposals that the microbiota can influence de­ the infant's own microbiota might be affected by the mode of birth
pression, anxiety, and autism spectrum disorders (vaginal or cesarean), feeding method (breast or bottle fed), and
(MacQueen, Surette, & Moayyedi, 201 7). The exposure to antibiotics.
transfer of fecal microbiota from patients with Source: Mayer, E. A., Tillisch, K., & Gupta, A. (2015). Gut/brain axis and the
major depressive disorder (MOD) to animals microbiota. The Journal of clinical investigation, 1 25(3), 926-938.

(continued)

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. S(;anned, or duplicated, in whole or in part. Due IO electronic rights.. some third p:lrty conlent may be s.uppres.sed from the cBook andfor eChapter(s).
Editorial review has deemed that any s.uppres.sed ron1ent does no1 macerially affecl the overall learning experience. Ccng:ige Learning reserves. the right to remcwe addicion:il contenl at any time if subsequent rights restrictions require it.
558 C H APTER 1 6 Psychopathology

Building Better
THE G UT M ICROBIOTA AND M ENTAL DISORDERS ( Continued)
HEALTH
�"'
''"
'""
' '
''"
' ""'
''"
' '
'"'
''"'""''"'''"'''"'''"'''"'''"'''"'''"'''"'""''""'"'''"'''"'''"'''"''"''''"'''"'"'"'''"'''"''"'''"'''"'''"'''"'''"'''"''"''''"'''"''"'""''''"''"''""''"'''"'''"''"''''�

produced behavioral changes in the animals that were participants? Participants with MDD who received a
analogous to MDD (Naseribafrouei et al., 201 4). probiotic product showed larger improvements on the
These reports have been featured prominently in Beck Depression I nventory than participants receiving a
the popular press. Global sales of probiotics, products placebo (Akkasheh et al., 201 6). However, the investi­
containing live bacteria and yeasts, are expected to gation of gut microbiota influences on mental disorders
reach $ 1 00 billion by 2020 (MacQueen et al., 201 7). is still in its infancy, and the data so far do not support
Is this enthusiasm warranted by research with human massive spending on probiotic products.

�'''"''""''"'''''"''�"'"''"'�

Across entire lifetimes, as many as 65 percent of the population experiences a disorder at

least once (Moffitt et al., 2010). Worldwide, numbers of people with mental disorders are
higher than in the United States because poverty, war, and other environmental factors
contribute to increased prevalence (Kessler et al., 2007).

Autism Spectrum Disorder (ASD)

The word autism literally means "within oneself." Autism spectrum disorder
(ASD) is one of several neurodevelopmental disorders, in which the onset of symp­
toms occurs during development (APA, 2013). According to the DSM-5, ASD is
characterized by deficits in two behavioral domains: social communication and
interaction and restricted, repetitive patterns of behavior, interests, or activities
(APA, 2013). ASD is one of several disorders with a gender difference in risk. B oys
are about four times more li kely to b e diagnosed with ASD than girls (Blumberg
et al., 201 3).
Autism is described as a spectrum because the severity of the observed deficits and
the course of the disorder varies widely from individual to individual. Some children
make relatively normal adjustments, but 30-60 percent will be intellectually disabled
(Amaral, Schumann, & Nordahl, 2008; Matson & Shoemaker, 2009). Most children
with ASD show symptoms by the age of 18 months, whereas 25-40 of children with
ASD percent develop normally until the age of 1 8-24 months, when they begin to
regress (Werner & Dawson, 2005). Diagnosing ASD in school children has become
more common (Blumberg et al., 20 13). These time courses might represent different
sets of causal factors, although the behavioral outcomes are indistinguishable.
ASD diagnoses have increased rapidly in the past few decades (• Figure 16.3).
Parent reports indicate that about 1 child in 68 has been diagnosed with ASD
(Christensen, 2016). This represents a significant increase from the 3 to 6 children in
10,000 reported prior to 1990 (Wing, 1993). Rate increases might reflect a genuine rise
in the incidence of the disorder, a relaxation of diagnostic criteria, or a combination
of both factors (Barbaresi, Katusic, Colligan, Weaver, & Jacobsen, 2005). In the United
States, individuals can receive a medical diagnosis of ASD based on DSM-5 criteria
or be educationally verified by school personnel based on criteria in the Individuals
with Disabilities Education Act (Ramsey, Kelly-Vance, Allen, Rosol, & Yoerger, 2016).
The use of different criteria makes prevalence difficult to assess. Among cases diag­
autism spectrum disorder (ASD) nosed after the age of seven years, the vast majority are "mild;' suggesting that some
A lifetime disorder characterized increases in prevalence rates are due to greater awareness, changes in the application
by impairments in social
interaction and communication of diagnostic criteria, or increased availability of special education services (Blumberg
and range of interests. et al., 2013).

Copyright 2019 Cengage Learning. All Rights Reserved. May not b e copied, scanned, o r duplicated, I n whole o r in part. WCN 02-200-202

Copyright 2019 Cengage Leaming. All Rights Reserved. May not be copied. scanned, or duplicated, in wholeor in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
 Autism Spectrum Disorder (ASD) 559

c 14 • Figure 16.3 Rates of

e
:!:? Autism Spectrum Disorder
:c
12 Are Increasing Rates of
(,)
0 10 autism spectrum disorder
0
q have increased dramatically in
Gi
8 recent years, but the reasons
Q. for the increase remain poorly
QI
6
(,) understood.
c
QI 4
Cij
>
e 2
D..

0
2000 2002 2004 2006 2008 201 0
Surveillance year

Causes of ASD
The causes of ASD remain unknown. Evidence from family and twin studies indicates
that ASD is influenced by genetics (Frazier et al., 2014). The concordance rate (see
Chapter 5) in identical twins is 76 to 88 percent (Ronald & Hoekstra, 20 1 1 ) . Relatives
of people with ASD have elevated levels of autistic traits compared to people with no
relatives with ASD (Constantino et al., 2009). Autistic traits are continuously distrib­
uted across the human population and only reach the level of a diagnosable disorder
in a smaller group of individuals (Baron-Cohen, Wheelwright, Skinner, Martin, &
Clubley, 200 1).
Genes associated with ASD regulate brain development (Sakai et al., 201 1 ;
Vorstman et al., 2017; Yang & Gill, 2007) and specifically influence synaptic changes
(Persico & Bourgeron, 2006). No single gene contributes to a person's susceptibility
to all aspects of ASD. However, one of the most reliable signs of ASD is language
delay, and studies combining genetic vulnerability for ASD and language difficulties
have pinpointed a candidate gene on chromosome 7 for "age at first word" (Alarcon
et al., 2008). Another candidate gene, the CNTNAP2 gene, is linked to both ASD
and dyslexia, a developmental reading disorder discussed in Chapter 1 3 (Stoodley,
2014). Otherwise, general tendencies managed by large pools of genes are likely to be
involved (Skafidas et al., 2012). People with ASD are more likely to have relatives who
are engineers and scientists, whose thinking is highly systematic, than relatives who
are artists and poets, whose thinking is more emotional and empathic (Alarcon et al.,
2008; Baron-Cohen & Belmonte, 2005; Persico & Bourgeron, 2006).
Genetic predispositions for ASD likely interact with multiple environmental factors
(Happe, Ronald, & Plomin, 2006). One environmental risk factor for ASD is perina­
tal complications, or complications surrounding the birth of the individual (Ronald &
Hoekstra, 20 1 1 ) . Advanced paternal age at conception (mid-30s or more) is correlated
with increased risk of producing a child with autism (Janecka et al., 2017; Shelton,
Tancredi, & Hertz-Picciotto, 20 10). Exposure to infection, pesticides, and nutritional
factors have also been implicated as possible risks for ASD (Hamlyn, Duhig, McGrath,
& Scott, 2013; Rossignol, Genuis, & Frye, 2014).
Maternal use of antidepressants, selective serotonin reuptake inhibitors (SSRis)
in particular, during or prior to pregnancy increases the likelihood of giving birth to
a child with ASD (Hendrick, 2016; King, 2017; Mezzacappa et al., 20 1 7) . Boys with
ASD were three times as likely as typically developing boys to have been exposed
prenatally to SSRis (Harrington, Lee, Crum, Zimmerman, & Hertz- Picciotto, 2014).
As we mentioned in Chapter 4, children with ASD have abnormal blood levels of
serotonin, although the implications for this difference on the functioning of the
nervous system is unknown.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
560 C H APTER 1 6 Psychopathology

Birth to 2 years
• Figure 1 6.4 Vaccines and Autism
Spectrum Disorder (ASD) Are Not 1 8,000-18,258 0
Linked In spite of significant scientific
evidence to the contrary, many people 1 5,000-15,258
continue to believe that vaccination
1 2,000-12,258 25
is responsible for recent increases in 25
ASD diagnoses. There are a number of 21
9000-9258
markers of vaccination influence that 17
have been investigated, and none has 6000-6258
I/)
shown evidence of vaccination effects c
"
on ASD. In this example using data Cl
0
3000-3258
c
from approximately 1 ,000 children, :I
E 201-311
.§
researchers traced rates of ASD as a
function of total cumulative immuno­ " 13
1 76-200 18
gens (molecules that can provoke an ·:;;
10
immune response) from vaccines given '5
25
E:I
1 5 1 -175
over the first two years of life. As you 25
can see in this figure, children later I.) 126-150
cu
diagnosed with ASD do not differ from
healthy control children. ;§ 101-125

Source: Destefano, F., Price, C. S., & 76-100

Weintraub, E. S. (201 3). Increasing expo­
sure to antibody-stimulating proteins and 5 1 -75
polysaccharides in vaccines is not associated
with risk of autism. The journal of Pediatrics, 26-50
1 63(2), 561 -567. D Controls
0-25 0 • ASD cases
0

0 10 20 30 40 50
Percent

ASD is also linked to abnormal responses of the maternal immune system during
pregnancy (Bauman et al., 201 3). Maternal antibodies routinely cross the placenta to
provide protection for the fetus. However, in approximately 12 percent of mothers of
children with ASD but in no mothers with typically developing children, maternal
antibodies that target fetal brain proteins were identified. When these antibodies were
administered to pregnant rhesus monkeys, their male offspring showed brain abnor­
malities and inappropriate social behaviors.
One certainty regarding the causes of ASD is that it is not caused by vaccines
(see • Figure 16.4). A meta-analysis of more than one million children shows
absolutely no links between ASD, vaccination in general, vaccination with the
measles-mumps-rubella combination vaccine, or thimerosal, a mercury-containing
preservative used in some vaccines (Taylor, Swerdfeger, & Eslick, 2014).

Brain Structure and Function in ASD

One leading theory of ASD suggests that brain development is abnormally acceler­
ated through early childhood, producing brain enlargement, which is then followed
by a period of deceleration (Amaral et al., 2008). Consistent with this view is the
finding that infants eventually diagnosed with ASD have much higher levels of cir­
culating neurotrophins than healthy infants within a few days of birth (Nelson et al.,
200 1 ) . High levels of neurotrophins may lead to less apoptosis and larger brain size
(see Chapter 5). Larger head size at birth in children who are later diagnosed with
ASD might also be the result of excess cerebrospinal fluid (CSP; see Chapter 2) in

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1cnt docs no1 macerially affecl the overall learning experience. Ccng:igc Le:irning reserves the right to remcwe addicion:il contenl at any time if subsequent rights restrictions require it.
 Autism Spectrum Disorder (ASD) 561

the subarachnoid space. The amount of excess CSF observed in an MRI at the age of
six months was predictive of not only a diagnosis of ASD but also the eventual
severity of ASD symptoms (Shen et al., 20 13).
An alternate view of brain anatomy in ASD suggests that the structure of mini­
columns, representing the smallest units of processing in the prefrontal cortex, is
different in individuals with ASD compared to healthy controls (Casanova, Switala,
Trippe, & Fitzgerald, 2007; Casanova et al., 2006; Opris & Casanova, 2014) (see
• Figure 16.5). The number of neurons within each minicolumn in the brains of
people with ASD is normal, but the distance between minicolumns is reduced
(Opris & Casanova, 2014). These findings are consistent with differences in connec­
tivity that favor local or detail-focused processing over global processing (Casanova
et al., 2007; Casanova et al., 2006; Opris & Casanova, 2014). The additional finding
that the brains of three distinguished scientists without deficits in language and
sociability showed minicolumn structure similar to that found in patients with
ASD suggests that minicolumn dimensions might account for the extreme focus of
interests found in ASD and possibly savant behavior ( Casanova, Switala, Trippe, &
Fitzgerald, 2007).
Other brain structures associated with ASD include the cerebellum, amygdala,
and hippocampus. Decreased cerebellar cortical volume is a very important bio­
marker for ASD (Stoodley, 2014). The degree of structural differences in the cere­
bellum compared to typically developing individuals is correlated with the severity
of behavioral symptoms. Although earlier researchers have reported abnormalities in
the development of the amygdala, a longitudinal comparison of children with ASD
and normally developing controls found similar changes in amygdala volume over

• Figure 1 6.5 Minicolumn

Differences in Autism
Spectrum Disorder
Researchers have observed
differences in the cortical mini­
column organization between
people with autism spectrum
disorder and healthy controls.
The differences are consistent
with more local, detailed
processing rather than global
processing.

(a) Healthy controls

(b) Individuals with autism

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
562 C HAPTER 1 6 Psychopathology

time (Barnea-Goraly et al., 2014). Within the ASD group, the volume of the right
amygdala predicted the capability of making appropriate eye contact. The children
with ASD did not differ from the healthy controls in the volume of the left hippocam­
pus, but their right hippocampus was relatively enlarged (Barnea-Goraly et al., 2014).
Over the course of development, the children with ASD experienced normalization of
their right hippocampal volume due to reductions that did not occur in the normally
developing group.
Other researchers have explored brain connectivity in ASD (Ecker, 20 1 7). In
Chapter 1 3 , we noted differences in lateralized networks between healthy controls
and individuals with ASD. Scans of 6-month-old infants at high risk of ASD due
to family history with later diagnosis for ASD showed early differences in white
matter development, including the development of the corpus callosum (Wolff
et al., 2012).
In previous chapters, we discussed roles of the default mode network (DMN) in
processing information about the "self;' and the structures and connectivity patterns of
the DMN are suspected to contribute to ASD (Padmanabhan, Lynch, Schaer, & Menon,
2017). Core features of ASD involve social impairments, self-related cognitive process­
ing, and difficulty inferring the mental states of others. These are precisely the types of
cognitive processes and behavior linked to the DMN.
Dysfunctions in mirror system function (see Chapter 8) were suggested as pos­
sible correlates of ASD because mirror system function might contribute to empathy,
imitation, and language (Iacoboni & Dapretto, 2006; Iacoboni & Mazziotta, 2007).
However, a meta-analysis found no evidence of a global deficit in mirror functioning
in ASD (Hamilton, 2013). A possible role for mirror system function in ASD con­
tinues to be debated (Gallese, Rochat, & Berchio, 2013; Schulte-Ruther et al., 2016;
Schunke et al., 2016).
At a more molecular level, individuals with ASD show signs of abnormal microg­
lia (see Chapter 3; Werling, 2016). Microglia might contribute to ASD through their
participation in the pruning of synapses during development. In rodents, the failure
to prune immature, less effective synapses during development results in behaviors
similar to those observed in ASD. A role for microglia might also explain the gender
differences seen in ASD. Candidate genes for ASD that have higher expression in
males than females include some that influence glial cells, including the microglia
(Werling, 2016).

Treatment of ASD
ASD is usually treated with intensive, early-childhood learning experiences pro­
vided during most of the child's waking hours (Masi, DeMayo, Glozier, & Guastella,
20 1 7). For high-functioning children with spontaneous language prior to the age
of 3 to 5 years, this aggressive intervention can produce nearly normal behavioral
outcomes (Smith & Lovaas, 1 998).
Efforts to use medications to improve core behavior problems (social related­
ness and ritualistic behavior) in children with ASD have been ineffective (Buitelaar,
2003). Only two medications, both antipsychotic drugs intended to reduce self­
injurious behavior among the most severely affected individuals, have been approved
in the United States for the treatment of ASD (McPheeters et al., 2011). Many addi­
tional medications are prescribed "off label;' or without Federal Drug Administration
approval for ASD, including antidepressants. A disturbing 35 percent of children with
ASD in one sample had been prescribed at least one off-label drug, and 9 percent were
taking three or more off-label drugs (Rosenberg et al., 2010).
Based on reports that people with ASD show evidence of excess peptides from
gluten (found in wheat) and casein (found in dairy products), many families exclude
these food sources from the diets of children with ASD. However, controlled studies do
not support these diet changes for reducing core symptoms of ASD (Millward, Ferriter,
Calver, & Connell-Jones, 2008).

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ contcnl at any time if subsequent rights restrictions require ii.
 Attention Deficit Hyperactivity Disorder {ADHD) 563

Behavioral
Neuroscience APPLIED BEHAVIOR ANALYSIS
GOES TO WORK
. . . . . . . . . . . . .. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

E arly work by Ivar Lovaas and his colleagues at UCLA

established the efficacy of applying principles of op­
erant conditioning, or the pairing of consequences and
target behaviors (see Chapter 1 2), to im prove the lan­
guage and social skills of children with ASD (Smith &
Lovaas, 1 998). Originally, such applications were known
as "behavior modification." Eventually, the preferred
term became applied behavior analysis or ABA. While
not restricted to the treatment of children with ASD or
other neurodevelopmental disorders, ABA is the major
approach used in these situations (see • Fig u re 1 6 .6).
Board certification in ABA is available through the
non profit Behavior Analyst Certification Board (BACB) at
different levels depending on an individual's attainment
of a bachelor's, master's, or doctoral degree. Certifica-
•
tion at the bachelor's deg ree level gives the person the • Figure 16.6 Autism Spectrum Disorder Is Treated with
title of board certified assistant behavior analyst, and App l ied Behavior Analysis In the absence of medications that
certification at the master's deg ree level gives the per­ improve the core symptoms of autism spectrum disorder, the
son the title of board certified behavior analyst (BACB, only effective method for treating this disorder remains applied
201 7). Additional certification is available at the doctor­ behavior analysis (ABA).
al level. Approved university training is typ ically housed
in either psychology or education departments. circumstances in which the target behavior occurs and
Behavior analysts work with clients by using learn­ possible rewarding mechanisms already in place that may
ing principles to change the frequency of behaviors, be maintaining the behavior and designs a plan to change
such as increasing language output or decreasing un­ the frequency of the target behavior. In the case of autism
wanted, self-stimulation behaviors such as rocking, hand spectrum disorder, teams of analysts take turns working
flapping, and head banging. The analyst considers the with a child through most of the child's waking day.

Attention Deficit Hyperactivity Disorder (ADHD)

Symptoms of attention deficit hyperactivity disorder (ADHD) include inattentive­
ness, impulsivity, and hyperactivity (APA, 2013). Individuals can be diagnosed with
inattentiveness alone without impulsivity/hyperactivity, impulsivity/hyperactivity
alone without inattentiveness, or combined inattentiveness and impulsivity/hyperac­
tivity. In 20 1 1 , 1 1 percent of children between the ages of 4 and 17 had been diagnosed
with ADHD in the United States, an increase of 42 percent over rates of ADHD in 2003
(Visser et al., 2014). Symptoms of ADHD can continue beyond childhood, affecting
approximately 4 percent of adults (Kessler et al., 2007). ADHD is diagnosed at least
twice as frequently in males as in females, and females are more likely to exhibit inat­
tention without impulsivity and hyperactivity (APA, 2013).
Clinicians debate whether ADHD is overdiagnosed or underdiagnosed (Brownlee
et al., 20 17; Sciutto & Eisenberg, 2007). Diagnosis of ADHD is controversial because
many criteria for the disorder involve normal behaviors (see • Figure 16.7). For exam­
ple, the criteria include "often avoids, dislikes, or is reluctant to engage in tasks that
require sustained mental effort (such as schoolwork or homework; for older adoles­ attention deficit hyperactivity
cents and adults, preparing reports, completing forms, reviewing lengthy papers)" disorder (ADHD) A disorder
first diagnosed in childhood,
(APA, 2013, p. 59). Angold, Erkanli, Egger, and Costello (2000) found that more than characterized by inattention,
half of the children in a large sample taking stimulant medications for ADHD did not hyperactivity, or both.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from thc cBook andfor eChapler(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affect the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if su�uent rights restrictions require it.
564 C H APTER 1 6 Psychopathology

• Figure 1 6.7 Rates of ADHD

Are Not Geographically
Consistent One of the
concerns about the process
of diag nosing ADHD is that
rates of diagnosis show strong
regional variations. Although
diagnosis of ADHD is related . 1 4-15.9%
to socioeconomic status, there D 1 1-13.9%
is no theory that accounts . 9.6-10.9%
. 8.0-9.5%
for the much higher rates 0 5.6-7.9%
of ADHD diagnosis in the
southeast compared to other
regions of the country. These
...
data suggest that the diag­
nostic criteria are not being
,.
applied in any consistent way. �...
••

meet even relaxed diagnostic criteria for the disorder. When vignettes describing case
studies were sent to 1,000 child psychologists, psychiatrists, and social workers, 17 per­
cent of the clinicians diagnosed ADHD incorrectly in healthy children (Bruchmiiller,
Margraf, & Schneider, 2012).

Causes of ADHD
The heritability of ADHD has been estimated to be 70 percent or possibly higher
(Faraone & Mick, 2010). The mechanism for this genetic influence is currently
unknown, and it is likely that multiple genes are involved. Genes involved with dopa­
minergic systems are a logical starting place. Brain structures consistently implicated
in ADHD, such as the basal ganglia and prefrontal cortex, are rich in dopaminergic
neurons. Traditional medications used for ADHD, which include methylphenidate
(Ritalin), dextroamphetamine (Dexedrine or Dextrostat), and mixed amphetamine
salts (Adderall), are known dopamine agonists. Research has therefore focused on
genes associated with dopamine, including dopamine transporter genes (Albrecht
et al., 2014; Klein et al., 2 0 1 7; Spencer et al., 2013).
Although genetic influences on ADHD are substantial, environmental factors
alone or in conjunction with candidate genes contribute to the prevalence of the
disorder. Among environmental risk factors for ADHD are lead contamination, low
birth weight, and prenatal exposure to tobacco, alcohol, and other drugs (Banerjee,
Middleton, & Faraone, 2007).

Brain Structure and Function in ADHD

methylphenidate (Ritalin) A close
relative of amphetamine that The fact that people with known frontal lobe damage behave similarly to those with
is prescribed to treat attention
deficit hyperactivity disorder. ADHD has led to interest in the frontal lobes. Specifically, both groups have problems
dextroamphetamine (Dexedrine with organization, impulsivity, emotional behavior, and sustained attention. However,
or Dextrostat) A dopamine the frontal lobes are not the only structures of interest in ADHD. Smaller volume in
agonist used to treat some cases
of attention deficit hyperactivity the amygdala, basal ganglia, hippocampus, and the brain as a whole are associated with
disorder. ADHD (Hoogman et al., 2017). Researchers have also identified differences between
Adderall A combination of healthy controls and individuals with ADHD in the prefrontal cortex, the anterior
amphetamine salts prescribed
to treat attention deficit cingulate cortex, and the circuits that connect these areas (Frodl & Skokauskas, 20 12;
hyperactivity disorder. Khadka et al., 20 16). White matter disruption is also associated with ADHD. The degree

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02·200·202

Copyright 2019 Cengage Leaming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.�d con1ent docs no1 macerially affecl the overall learning experience. Ccng:ige Le:irning reserves the right to remcwe addicion:il contenl at any time if subsequent rights restrictions require it.
 Attention Deficit Hyperactivity Disorder {ADHD) 565

• Figure 16.8 Brain Maturity

Differences in ADHD Some
researchers suggest that a number
of children diagnosed with ADHD
experience delayed brain mat­
uration relative to their peers.
Peak cortical thickening occurs in
healthy children around the age
of 7.5 years but was not seen in
children with ADHD until about
three years later. This finding
implies that some children with
ADHD might eventually "catch
up" to their peers, although others
• Greater than 2 years' delay continue to experience symptoms
0-2 years' delay throughout adulthood.

of white matter disruption in the corpus callosum, which connects the right and left
cerebral hemispheres, predicts the severity of ADHD symptoms (Ameis et al., 2016).
Some researchers have argued that ADHD involves delays in brain maturation
(Hoogman et al., 20 17; Shaw et al., 2007; Vaidya, 20 12) (see • Figure 16.8). Peak cor­
tical thickness, a measure of brain maturation, occurred in healthy controls around
age 7.5 years but not until age 10.5 years in the children with ADHD. As we noted in
Chapter 5, cortical thickening followed by some degree of thinning is a normal part
of adolescent brain development. Cases in which symptoms of ADHD persisted into
adulthood showed an increased rate of cortical thinning compared to healthy controls,
while individuals whose symptoms disappeared as they matured experienced either
cortical thickening or minimal thinning during adolescence (Shaw et al., 2013).
Smaller volume of the caudate nucleus, a part of the basal ganglia, is associated
with ADHD (Castellanos et al., 1994; Filipek et al., 1997; Mataro et al., 1997; Swanson,
Castellanos, Murias, LaHoste, & Kennedy, 1998). However, this difference between
individuals with and without ADHD disappears by the age of 16 (Krain & Castellanos,
2006), lending further support to the view of ADHD as a problem of maturation.
Behavioral neuroscience continues to move in the direction of considering networks,
like the default mode network (DMN), rather than abnormalities in specific structures
or regions of the brain as the source of abnormal behavior. Deviations from normal
brain network growth were predictive of a diagnosis with ADHD and poor performance
in sustained attention, or on-task behavior (Kessler, Angstadt, & Sripada, 2016).

Treatment of ADHD
Children with ADHD are treated primarily with medication, either alone or in combi­
nation with behavioral therapy similar to that used to treat ASD. The use of medication
for ADHD in the United States, which is five times greater than in any other nation, has
been the subject of considerable criticism. Nonetheless, when investigated using the
"gold standard" of the double blind placebo-controlled design (see Chapter 4), medica­
tion provides benefits for the majority of children with ADHD (Faraone & Mick, 20 10).
The use of stimulant medication to treat ADHD resulted from an accidental dis­
covery. In 1937, Charles Bradley administered the stimulant Benzedrine, a type of
dextroamphetamine, to children referred to him for learning and behavior problems.
Bradley ( 1937) observed that the children responded with spectacular improvement in
school performance while becoming emotionally subdued.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
566 C HAPTER 1 6 Psychopathology

The most commonly prescribed drugs for ADHD are the closely related stim­
ulants methylphenidate (Ritalin), dextroamphetamine, and amphetamine salts
(Adderall). The amphetamine drugs act as dopamine and norepinephrine reuptake
inhibitors and increase the release of these neurotransmitters. Methylphenidate acts
as a dopamine reuptake inhibitor (see Chapter 4). The positive outcomes resulting
from the use of dopamine agonists has led to the suggestion that ADHD is associated
with lower levels of dopamine activity (Volkow et al., 2009). Although most patients
tolerate these medications well, serious side effects including loss of appetite and sleep
disturbance can occur (Ogrim, Hestad, Brunner, & Kropotov, 20 1 3). Nonstimulant
drugs such as atomoxetine (Strattera), a norepinephrine reuptake inhibitor, are also
prescribed (Prasad & Steer, 2008). However, atomoxetine is associated with increased
suicidal thoughts (U.S. Food and Drug Administration [FDA], 20 13).
A recent and troubling trend in the treatment of ADHD has been to prescribe anti­
psychotic medications in addition to stimulant medications (Bussing & Winterstein,
2012). Antipsychotic medications usually produce either a direct or indirect suppres­
sion of dopamine function, which is not consistent with the stimulant medications'
agonistic effect on dopamine (Bussing & Winterstein, 2012) or with a hypothesis impli­
cating inadequate dopamine activity as the source of ADHD symptoms.

I N T E R I M S U M M A RY 1 6 . 1

11
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111

Summary Points
1. A mental disorder is defined as "a syndrome characterized by clinically significant
disturbance in an individual's cognition, emotion regulation, or behavior that reflects
a dysfunction in the psychological, biological, or development processes underlying
mental functioning." (L01)
2. Autism spectrum disorder (ASD) is heavily influenced by genetics and is correlated
with abnormal development in brain structures and connectivity. Early, intense beha­
vioral intervention is the typical treatment for ASD. (L02)
3. Attention deficit hyperactivity disorder (ADH D) is characterized by short attention
span and high levels of motor activity. Abnormal functioning of the frontal lobe and
basal ganglia might contribute to ADHD. ADHD is typically treated with stimulant
medication with or without behavioral therapy. (L03)

11 Review Questions
1. What are the leading hypotheses for explaining the causes of ASD and ADHD?
2. What structural and functional brain correlates characterize ASD and A D H D?
11111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111\llllllltlllllll

schizophrenia A disorder
characterized by hallucination,
delusion, cognitive impairment,
mood disturbance, and social
withdrawal.
Schizophrenia
delusion A false belief or opinion
that is strongly held in spite Schizophrenia dramatically disrupts many of the basic capacities that are central to
of conclusive, contradictory
human experience-perception, reason, emotion, movement, and social engagement. A
evidence.
hallucinations A false or distorted diagnosis of schizophrenia requires at least two of the following to be present most of the
perception of objects or events. time during a single one-month period: delusions (unrealistic thoughts), hallucinations
positive symptom An abnormal (false perceptions), disorganized speech, grossly disorganized or catatonic behavior, and
behavior, such as hallucination
and delusion, that does not occur negative symptoms (diminished emotional expression or avolition) (APA, 2013).
in healthy individuals but occurs Symptoms of schizophrenia are divided into categories of positive and negative
in people with schizophrenia. symptoms. Positive symptoms are behaviors that are not expected to occur normally,
negative symptom A normal and
expected behavior that is absent such as hallucinations and delusions. Instances of these behaviors are frequently
due to schizophrenia. referred to as "psychotic episodes:' Negative symptoms, such as diminished emotional

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Cc.ngage Leaming. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook andfor cChapter(s).
Editorial review has deemed tha1 any suppressed content does not materially affect the overall learning experience. Ccngagc Leaming reserves the right 10 remove additional conten1 at any time if subsequent rights restrictions require ii.
 Schizophrenia 567

expression and avolition (lack of motivation), occur when normal behaviors are miss­
ing. Healthy people are emotionally expressive (see Chapter 14) and motivated (see
Chapter 9), so disruptions to these behaviors in schizophrenia represent the absence
of normal behavior. Although the distinction between positive and negative symptoms
may appear arbitrary, these symptoms differ in their underlying causes and responses
to treatment.
Lifetime prevalence of schizophrenia is about 0.7 percent, or 7 individuals out
of 1000 (McGrath, Saha, Chant, & Welham, 2008). Most cases of schizophrenia are
diagnosed for the first time in individuals between the ages of 1 8 and 25 years of age,
although a sizable minority of cases appear for the first time after age 40 (Howard,
Rabins, Seeman, Jeste, & Late-Onset, 2000). About 60 percent of patients with schizo­
phrenia are male (McGrath, Saha, Chant, & Welham, 2008).

Genetic Contributions to Schizophrenia

Substantial evidence supports a genetic predisposition for schizophrenia. The con­
cordance rate is about 50 percent in identical twins and about 17 percent in frater­
nal twins (Gottesman, 199 1 ) . As shown in • Figure 16.9, the odds that a person will
develop schizophrenia increase as more closely related family members are diagnosed
with the disorder. Results of adoption studies also support a large role for genetics
in schizophrenia (Kety, Rosenthal, Wender, & Schulsinger, 1968). Genes are not the
entire story, however, as shown by the case of the Genain sisters, identical quadruplets
diagnosed with schizophrenia (DeLisi et al., 1984). Although all four sisters had schizo­
phrenia, their outcomes differed substantially. One sister graduated from a two-year
business college, married, and had two children, while her sisters' social functioning
was described as "grossly inadequate:'
The hunt to identify the genes responsible for schizophrenia is an active area
of research. Genome-wide association studies (GWAS) show that large numbers of
genes function abnormally in the brains of people with schizophrenia (Ripke et al.,
2013). Candidate genes for schizophrenia include genes affecting dopamine activity,

General population • Figure 1 6.9 The

Influence of Genetics on
Spouse of patie nt Schizophrenia A person's
First cousin odds of being diagnosed with
schizophrenia increase when
U ncl e/au nt closely related family members
have the disorder. The fact
Nephew/niece
that the odds of your being
Grandchild diagnosed with schizophrenia
Half sibling ••• increase if you marry a person
with schizophrenia might
Child reflect the tendency of people
to be attracted to others who
Sibling share some of their traits.
Source: Adapted from Gottesman

One parent I••

(1991).

Identical twin

0 10 20 30 40 50
Lifetime risk of developing schizophrenia (percent)

Copyright 2019 Cengage Learning. A l l Rights Reserved. May not b e copied, scanned, o r duplicated, I n whole o r in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent righ1s restrictions require it.
568 C HAPTER 1 6 Psychopathol ogy

neurodevelopment (see Chapter 5), serotonin activ­

(a) ity, and glutamate activity (Zai, Robbins, Sahakian, &
Kennedy, 20 17) .
Central fixation: • Candidate genes for schizophrenia overlap with those

]
3000-5000 ms
implicated in bipolar disorder, a mood disorder discussed
J in a later section (Owen, Craddock, & Jablensky, 2007).
•
Target at the left/right at In one case of identical triplets, two were diagnosed
6°, 1 2° or 18°: 1500 ms
with schizophrenia, whereas the third was diagnosed

I
with bipolar disorder (McGuffin, Reveley, & Holland,
1982). Candidate genes for schizophrenia also overlap
Central fixation • with those of autism spectrum disorder (Cross-Disorder
Group of the Psychiatric Genomics Consortium, 2013;
Gejman, Sanders, & Kendler, 20 l l).
One o f the most consistent findings i n schizophre­
(b) nia is the presence of dysfunctional eye movements, first
70 reported over one century ago (Diefendorf & Dodge,
�
0 1908). Because dysfunctional eye movements are also
t: 60
Q) found in many healthy relatives of people with schizo­
Q)
"C phrenia, eye movements provide a useful endopheno­
., 50
u
u type, or subtype of a pathological condition, that can
.,
"' 40 guide genetic investigations (Radant et al., 2015).
:;:::;
c:
., 30 Differences in eye movement between patients with
0 schizophrenia and healthy controls occurs in an antisac­
�
., 20 cade task (see • Figure 16. 10). Saccades are rapid shifts
'E in gaze from one fixation point to the next. In the anti­
Q) 10
�
Q) saccade task, you first focus at the center of the visual
Q.
0 field. When a stimulus appears in the periphery, you
Control Full sibling H igh risk Patient with
schizophrenia must look in the exact opposite direction, although our
normal impulse would be to look at the peripheral stim­
• Figure 16.1 0 A Possible Genetic Marker for ulus. Antisaccade errors (looking at rather than away
Schizophrenia Patients with schizophrenia and many of their from the peripheral stimulus) indicate problems with
close family members show abnormal saccades, or rapid shifts executive control and inhibition, which also characterize
i n gaze from one fixation point to the next. Dysfunctional
schizophrenia. Patients with schizophrenia make more
eye movements can be demonstrated using the antisaccade
errors in the antisaccade task than healthy people do
task, outlined in (a). After focusing on the dot in the center,
another dot will appear to the left or the right. The partici­ (Myles, Rossell, Phillipou, Thomas, & Gurvich, 2016).
pant's task is to inhibit the urge to look at the dot to the side Eye movement dysfunctions are linked to several
but rather to look away from it to the opposite side. After the schizophrenia candidate genes, making eye movement
trial, the participant again focuses on a central point to pre­ dysfunction useful as an endophenotype for schizophre­
pare for the next stimulus. (b) Results show that patients with nia (Hatzimanolis et al., 2015; Thibaut et al., 2015). Also
schizophrenia make many more errors that healthy controls. linked to dysfunctional eye movements is the frequent use
Full siblings of patients with schizophrenia and individuals of nicotine by patients with schizophrenia (see Chapter 4).
at high risk for schizophrenia due to their family history do Nicotine is known to improve saccadic performance in
not have as many errors as the patients, but they make more both patients and healthy controls (Petrovsky et al., 201 3).
errors than the healthy controls. Dysfunctional eye move­
Patients might self-medicate with nicotine, not because it
ments represent errors in behavioral inhibition and executive
control, and have been useful markers for the identification of improves saccadic control but because it provides similar
candidate genes influencing schizophrenia. relief from problems in more general executive function­
ing and inhibitory control.
Source: Caldani, S., Bucci, M. P., Lamy, J.-C., Seassau, M., Bendjemaa,
N., Gadel, R., et al. (2017). Saccadic eye movements as markers
of schizophrenia spectrum: Exploration in at-risk mental states. Environmental Influences
Schizophrenia Research, 1 81 , 30-37. doi: https://doi.org/1 0 . 1 0 1 6
/j.schres.201 6.09.003 on Schizophrenia
A number of environmental factors interact with genetic
vulnerability for schizophrenia. Rates of schizophrenia
are higher in urban environments (Van Os, 2004) and
saccade A rapid shifts in gaze from five times higher in lower than in middle or higher socioeconomic groups (Robins &
one fixation point to the next. Regier, 1991). It is not clear how much of the socioeconomic effect is causal and how

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Cengage Leaming. All Rights Reserved. May not be copied. scanned, or duplicated, in wholeor in part. Due IO electronic rights., some third p:lrty conlent m:iy be suppressed from the cBook :indfor eClupter(s).
Editorial review h:is deemed that any suppres.�d con1ent docs no1 m:iceri:illy affecl the ovcrall lc:irning experience. Ccng:ige Le:irning reserves. the right to remcwe addicion:il contcnl at any time if subsequent rights restrictions require it.
 Schizophrenia 569

much reflects the inability of people with schizophrenia to remain employed. Some of
this environmental influence may arise from poverty, poor nutrition, and the stress
related to racism (Boydell, & Murray, 2003; Boydell et al., 2001). Compared to native­
born individuals, migrants experience substantially higher rates of schizophrenia
(McGrath et al., 2008).
Living in an urban environment raises the likelihood of using marijuana, which
in turn is associated with psychosis (Fergusson, Horwood, & Ridder, 2005; Henquet,
2005; Onwuameze et al., 2013). Marijuana use might represent the efforts of an
individual to self-medicate for schizophrenia, but it is also associated with relapses
of psychotic symptoms in patients (Linszen, Dingemans, & Lenior, 1994). Patients
with schizophrenia have higher levels of endogenous cannabinoids (see Chapter 4)
in their cerebrospinal fluid and increased endogenous cannabinoid receptor density
compared to healthy controls, regardless of their history of cannabis use (Van Haren,
Cahn, Hulshoff Pol, & Kahn, 2013). Distortions in endogenous cannabinoid systems
might contribute to schizophrenia and use of marijuana could accentuate those dis­
tortions (Volk & Lewis, 2016).
Prenatal environmental factors might play a role in the development of schizo­
phrenia. The eventual development of schizophrenia in offspring is correlated with
mothers' difficulties during pregnancy (bleeding and diabetes), abnormal fetal devel­
opment (low birth weight and small head circumference), and birth complications
(emergency caesarean section, lack of oxygen) (Cannon, Jones, & Murray, 2002). It
is possible that a difficult birth triggers schizophrenia, infants vulnerable to schizo­
phrenia possess characteristics that predispose them to difficult prenatal and birth
processes, some combination of the two occurs, or the existence of a third, currently
unknown variable leading to both schizophrenia and birth complications might
account for these correlations.
A mother's exposure to famine or viral infection during her pregnancy can con­
tribute to the development of schizophrenia in her offspring (Khandaker, Zimbron,
Lewis, & Jones, 2013). People recently diagnosed with schizophrenia have higher levels
of viral enzymes in their brains and cerebrospinal fluid (CSF) than healthy controls
(Karlsson et al., 200 1 ) . People born between January and April (in the northern hemi­
sphere) are slightly more likely than people born at other times of the year to be diag­
nosed with schizophrenia (Davies, Welham, Chant, Torrey, & McGrath, 2003). During
the winter flu season, the patients' pregnant mothers could have increased exposure to
viruses, especially in colder climates (Cannon, Kendell, Susser, & Jones, 2003). Season
ofbirth effects are linked to a role for vitamin D deficiency in schizophrenia (McGrath,
Eyles, Pedersen et al., 2010).

Brain Structure and Function in Schizophrenia

Given the dramatic behavioral deficits found in schizophrenia, we might expect asso­
ciated brain abnormalities to be obvious. Unfortunately, it is difficult to separate the
effects of schizophrenia from other factors such as aging and medication history.
Many patients with schizophrenia have enlarged ventricles, as shown in
• Figure 1 6 . 1 1 . The presence of enlarged lateral ventricles distinguishes between
an identical twin who has schizophrenia and the twin who is healthy (McNeil,
Cantor-Graae, & Weinberger, 2000). Enlarged ventricles represent a loss of neurons
in adjacent areas. Volume in the nearby hippocampus is smaller than normal in
some individuals with schizophrenia (Stefanis et al., 1999). In particular, reduced
activity of glutaminergic neurons in the dentate gyms and its output, the mossy
fiber pathway (see Chapter 12), could explain the cognitive confusion experienced
by patients with schizophrenia (Tamminga, Stan, & Wagner, 2010). The role of the
hippocampus in stress (see Chapter 14) could explain links between the onset and
course of schizophrenia and stress levels.
Lower activity in the frontal lobes, or hypofrontality, is associated with nega­
tive symptoms of schizophrenia, such as mood disturbance and social withdrawal

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ contcnl at any time if subsequent rights restrictions require ii.
570 C HAPTER 1 6 Psychopathology

• Figure 1 6.1 1
Schizophrenia Is Associated
with Enlarged Ventricl es MRI
images of the brains of a pair
of identical twins show the
discrepancy between normal
ventricles and the enlarge­
ment of ventricles found in
some people who have schizo­
phrenia. The twin on the left is
healthy; the twin on the right
has schizophrenia.

(Andreasen et al., 1997). As shown in • Figure 16. 12, people with schizophrenia show
lower levels of frontal lobe activity than healthy controls both during rest and during
difficult cognitive tasks (Weinberger, Aloia, Goldberg, & Berman, 1994). Differences in
frontal lobe activity can be used to distinguish between an identical twin with schizo­
phrenia and the healthy member of the pair (Berman, Torrey, Daniel, & Weinberger,
1992). Abnormal frontal lobe activity might represent a more widespread problem in
the default mode network (DMN; see Chapter 1 1 ) . Activity in the DMN is markedly
abnormal in patients with schizophrenia, and the degree to which their DMN activity
differs from healthy control participants correlates with the severity of their positive
symptoms (Garrity et al., 2007).
Brains of people with schizophrenia are more symmetrical in structure and func­
tion than brains of healthy individuals, and people with schizophrenia are more likely
to be non-right-handed (Hirnstein & Hugdahl, 2014). In our species' ancient past,

• Figure 1 6.1 2
Hypofrontality F ronta l lobe
activity (toward the top of the
page) appears to be reduced
in people with schizophre-
nia when compared with
their healthy identical twins
engaged in the same tasks.
Active regions of the brain
appear red or yellow, and
inactive areas are green, blue,
violet, and black.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
 Schizophrenia 571

Participants with • Figure 1 6. 1 3

Typical Adolescents
Schizophrenia I s Associated
Schizop hrenia with Larger Losses of Gray
Matter in Adolescence Teens
typically experience a burst of
cortical gray matter growth at
puberty followed by a wave
of gray matter thinning that
extends into their early 20s.
Compared with their healthy
peers, teens diagnosed with
schizophrenia lose far more
gray matter.
Source: Thompson et al. (2001 ) .

schizophrenia might have risen in conjunction with cerebral lateralization and the
development of language (see Chapter 1 3) (Berlim, Mattevi, Belmonte-de-Abreu, &
Crow, 2003). Schizophrenia, according to this view, could be considered as a failure of
normal brain lateralization.
One of the puzzles surrounding schizophrenia has been its typical onset in late
adolescence or early adulthood. If candidate genes interact with environmental factors,
especially those involving prenatal development, why does it take so long for observ­
able symptoms to occur? One possible solution to this dilemma lies in observations of
brain development during the teen years (see Chapter 5). Teens typically experience a
burst of cortical gray matter growth at puberty followed by a period of cortical thinning
extending into their early 20s. As shown in • Figure 16.13, healthy teens experience rel­
atively little loss of gray matter, whereas teens diagnosed with schizophrenia experience
a loss that has been likened to a "forest fire" (Thompson et al., 2001). The adolescent
brain that is vulnerable to schizophrenia might experience either over-pruning or fail­
ure to produce sufficient synapses (Keshavan, Giedd, Lau, Lewis, & Paus, 2014).
Discovering the causes for early brain changes in schizophrenia will require further
research. One clue comes from research showing that cannabis use, but not tobacco
use, that continues past a first psychotic episode produces greater amounts of gray
matter loss compared to that experienced by non-cannabis users among patients with
schizophrenia (Van Haren, Cahn, Hulshoff Pol, & Kahn, 2012). As we observed earlier,
cannabis use might interact with existing abnormalities in the endogenous cannabi­
noid systems of people vulnerable to schizophrenia.

The Biochemistry of Schizophrenia

The dopamine hypothesis of schizophrenia rests on observations of psychosis resulting
from higher levels of dopamine activity along with the efficacy of dopamine antag­
onists in treating schizophrenia. As noted in Chapter 4, amphetamine, cocaine, and
L-dopa (used to treat Parkinson's disease) are potent dopamine agonists. Over time,

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent righ1s restrictions require it.
572 C H A PTER 1 6 Psychopathology

these drugs often produce behaviors similar to the positive symptoms of schizo­
phrenia, including hallucinations and paranoid delusions (Goetz, Leurgans,
Pappert, Raman, & Sterner, 200 1). It is difficult to distinguish between a person
Psychosis may result from
with schizophrenia and a person who has chronically abused stimulant drugs
conditions associated with (Brady, Lydiard, Malcolm, & Ballenger, 1991). The dopamine antagonists used
high levels of dopamine activity. to treat schizophrenia, also known as typical antipsychotic medications, act
Disorder: Schizophrenia
Drugs: Levodopa (L-dopa) by blocking the D2 dopamine receptor (see Chapter 4) and reduce psychotic
Methamphetamine symptoms that result from either schizophrenia or stimulant abuse. In addition
Cocaine
to possible abnormalities in the number of D2 receptors, patients with schizo­
phrenia also show evidence of greater dopamine synthesis and release (Howes,
Normal levels of dopamine McCutcheon, & Stone, 20 15).
activity
Why would excess dopamine activity lead to symptoms of psychosis?
Recall that dopamine assigns motivational significance to stimuli by deter­
Motor disturbances and relief mining which stimuli grab our attention and drive our behavior (Howes et al.,
from psychotic symptoms may 2015). Elevated presynaptic dopamine in patients with schizophrenia might
result from conditions
associated with low levels of
boost release in response to irrelevant stimuli, which in turn leads to delusional
dopamine activity. thought patterns. In healthy individuals, increased striatal dopamine leads to
Disorder: Parkinson's disease worse performance on cognitive tasks.
Drugs: Antipsychotics
To summarize evidence for the dopamine hypothesis, illustrated in
• Figure 16. 14, increases in dopamine activity are associated with psychosis,
and decreases in dopamine activity are associated with a reduction in psycho­
sis. However, the dopamine hypothesis is too simplistic. About one quarter of
• Figure 1 6.14 Correlations patients with schizophrenia fail to respond favorably to treatment with dopa­
between Dopamine Activity mine antagonists (Kane & Freeman, 1994). Although all licensed medications
Levels and Behavior Situations for schizophrenia block D2 receptors, newer atypical antipsychotic medi­
that lead to higher than normal cations provide relief from schizophrenia by affecting a wider range of neu­
levels of dopamine activity are rochemicals. For example, the atypical antipsychotic clozapine has a greater
associated with psychosis, while effect on serotonin systems than on dopamine systems (Syvalahti, 1994).
situations that lead to lower levels A disturbance in glutamate systems might provide the large-scale effects
of dopamine activity are associated that would account for the wide range of positive symptoms in schizophre­
with movement difficulties.
nia (Matosin & Newell, 2013). Patients with schizophrenia show evidence of
reduced numbers of glutamate receptors in their brains (Konradi & Heckers,
2003). Patients with schizophrenia experience a greater drop in glutamate activ­
ity in the brain as a result of aging compared to healthy controls (Marsman et al.,
2013). One of the useful animal models of schizophrenia for research purposes is the
administration of phencyclidine (PCP), which is a potent glutamate antagonist (Neill
et al., 2010). PCP is capable of producing several schizophrenia-like symptoms, includ­
ing auditory hallucinations, in humans. PCP not only blocks the NMDA glutamate
receptor but also serves as a dopamine agonist (Seeman, 2009). Psychosis due to PCP
use responds favorably to treatment with dopamine antagonists (Jentsch et al., 1997).
So which neurochemical, dopamine or glutamate, is most important in under­
standing schizophrenia? It appears that both reduced glutamate activity and increased
dopamine activity are associated with the symptoms of schizophrenia. Deciding which
system is the most influential is complicated by the reciprocal connections between
them (Howes et al., 20 15). It is possible that presynaptic disturbances in dopamine
function are responsible for the positive symptoms of schizophrenia while dysfunction
typical antipsychotic medication
A dopamine antagonist that is
in glutamate systems might underlie negative and cognitive symptoms.
used to treat schizophrenia or
psychosis.
atypical antipsychotic medication Treating Schizophrenia
One of several newer medications
used to treat schizophrenia that Treatment for schizophrenia was revolutionized with the discovery of the typical
are not dopamine antagonists.
phenothiazine One of a major
antipsychotics in the 1950s. The first of these were the phenothiazines, including
group of dopamine antagonists chiorpromazine (Thorazine) . French surgeon Henri Laborit was so impressed by the
used in the treatment of psychosis. calming effects of phenothiazines on his surgical patients that he encouraged his col­
chlorpromazine A commonly
prescribed dopamine antagonist, leagues in psychiatry to experiment with the drugs for treating psychosis. Subsequent
also known as Thorazine. research showed that phenothiazines were effective in treating the symptoms of

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Cengage Leaming. All Rights Reserved. May not be copied. scanned, or duplicated, in wholeor in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent does. no1 macerially affecl the overall learning experience. Ccng:ige Learning reserves. the right to remcwc addicion:il contcnl at any time if subsequent rights restrictions require it.
 Schizophrenia 573

0.35%
c:
• Figure 1 6.1 5 The
o - Discovery of Effective
·- ('CJ 0.30%
ca c
- Q) Medications for
5.. ::ii: 0.25% Schizophrenia Had Dramatic
0
0
Q. "' Effects The percentage of
en ; a;
::i I!! "E
0.20% the U.S. population that was
0 instituti onal ized due to mental
iii .!!!
..... ·-

0 0.15%
Q) c: 0 Begi n ning of disorders dropped almost in
Cl .!2
('CJ - 0.10% widespread use half in the years following the
- ::I
c: -
Q) � of typical antipsychotic discovery of antipsychotic
u "'
...
Q) -c: 0.5% medications medications.
Q.

0%
1 945 1 957 1 970
Year

schizophrenia. Typical antipsychotics primarily benefit patients with schizophrenia

by reducing positive symptoms. Negative symptoms, such as social withdrawal and
emotional disturbances, do not respond as much to these medications (Buchanan,
Breier, Kirkpatrick, Ball, & Carpenter, 1998). However, the discovery of the typical
antipsychotics allowed many patients, who previously required institutionalization,
to resume relatively normal lives. As shown in • Figure 1 6 . 1 5, the introduction of
typical antipsychotics in the 1950s coincided with a dramatic reduction in the num­
ber of mental patients who were institutionalized.
Unfortunately, antipsychotics are not specific in their choice of target. They block
dopamine receptors in multiple systems, including those controlling movement.
Tardive dyskinesia is a common and troubling side effect of these drugs. (Tardive
refers to "slow;' and dyskinesia means "difficulty moving:') Patients with tardive dys­
kinesia, like the patient shown in • Figure 16.16, exp erience tremors and involuntary

• Figure 16.1 6 Tardive

Dyskinesia Can Occur as a
Side Effect of Treatment
with Antipsychotic
Medications Antipsychotics
can produce tardive dyskine­
sia, characterized by intrusive,
involuntary movements and
tremors.

tardive dysk.inesia A chronic

disorder, characterized by
involuntary, jerky movements,
that occurs as the result of long­
term treatment with antipsychotic
medications.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from thc cBook andfor eChapler(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 macerially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if su�uent rights restrictions require it.
574 C HAPTER 16 Psychopathology

movements, especially in the face and tongue. Even when medication is discontinued,
movement difficulties often persist.
The causes of tardive dyskinesia remain elusive. As we noted in Chapter 8, voluntary
movement requires a balance between a direct pathway that facilitates movement and an
indirect pathway that reduces the force of movement. D2 receptors inhibit the indirect
pathway, so an increase of D2 receptors in response to prolonged medication could pro­
duce involuntary movements. Chronic blockage of D2 receptors might also distort the
balance between the direct and indirect pathways by stimulating a maladaptive plasticity
in connections between the basal ganglia and cortex (Aquino & Lang, 2014). Finally,
oxidative stress due to increased turnover of dopamine, which in turn increases produc­
tion of free radicals and hydrogen peroxide, might also contribute to tardive dyskinesia.
More than half of all patients today are treated with atypical antipsychotic medica­
tions such as olanzapine, clozapine, and rispiridone (Meltzer, 2000). As mentioned ear­
lier, clozapine has a stronger effect on serotonin receptors than on dopamine receptors.
An advantage of these newer medications is a reduction in negative symptoms, as well
as in positive symptoms (Rivas-Vazquez, Blais, Rey, & Rivas-Vazquez, 2000). However,
atypical medications are not necessarily safer than the typical antipsychotics. They pro­
duce weight gain and diabetes in many patients and still carry about the same risk of
producing tardive dyskinesia (Aquino & Lang, 2014). Side effects ofmedication can be
avoided in most cases with careful monitoring, but many patients receive poor medi­
cation management, indicated by doses above the recommended range and failure to
adjust doses based on observed behaviors (Young, Sullivan, Burnam, & Brook, 1998).
In addition to medication, psychosocial rehabilitation can be helpful (Mueser,
Deavers, Penn, & Cassisi, 20 13). Much to the embarrassment of Western medical
practitioners, the World Health Organization (WHO) published research suggesting
that patients with schizophrenia in developing countries, such as Nigeria, India, and
Colombia, were recovering more frequently than patients in wealthier countries, such
as the United States and European nations (Sartorius, 1986). Improved outcomes occur
when patients are given work and social skills training, education about schizophrenia
and the importance of medication, affordable housing linked to services, and informa­
tion about symptom management.

Bipolar Disorder
Bipolar disorders, also known as manic-depressive disorders, have been described as
a "bridge'' between the psychotic disorders, such as schizophrenia, and depressive dis­
orders in respect to their symptoms, family histories, and genetics (APA, 20 13, p. 123).
Bipolar disorder is characterized by at least one lifetime episode of mania, which is
often preceded or followed by a period of depression. Mania consists of"a distinct period
of abnormally and persistently elevated, expansive, or irritable mood, abnormally and
persistently increased goal-directed activity or energy, lasting at least one week and pres­
ent most of the day, nearly every day (or any duration if hospitalization is necessary)"
(APA, 2013, p. 124). Further symptoms include inflated self-esteem, decreased need
for sleep, higher-than-normal verbal output, flight of ideas, distractibility, increased
goal-directed activity, and excessive involvement in activities that have a high potential
for negative consequences (such as buying sprees or risky sexual encounters).
Many people with bipolar disorder experience depression as well as mania,
bipolar disorder A disorder although depression is no longer required for a diagnosis of bipolar disorder. In cases
featuring at least one lifetime in which depression does occur, the symptoms are the same as those found in major
episode of mania, which is often depressive disorder (APA, 20 13), which we discuss later in this chapter.
preceded or followed by a period
of depression. Worldwide, 48.8 million people have bipolar disorder (Ferrari et al., 2016). Rates
mania An unrealistically elevated, for bipolar disorder in the United States are similar to those of schizophrenia, with
expansive, or irritable mood about 0.8 percent of the population being affected. Women are more likely to be diag­
accompanied by unusually high
levels of goal-directed behavior or
nosed with bipolar disorder than men, but the ratio of 3:2 in bipolar is less extreme
energy that lasts about l week. than the 2:1 female-to-male ratio seen in major depressive disorder (Holtzman et al.,

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Cc.ngagc Leaming. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content maybe suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ content at any time if subsequent rights restrictions require ii.
 Bipolar Disorder 575

2016). The average age of onset for bipolar disorder

is 25 years (Kessler et al., 2007). Children and youth
under the age of 18 with symptoms of bipolar disor­
der are diagnosed with disruptive mood dysregula­
tion disorder instead (APA, 2013).
Bipolar disorder has been linked to enhanced
creativity. Kay Jamison ( 1993) argues that artists are
at greater risk for bipolar disorder than other people,
and she includes the poet William Blake, composers
Handel and Mahler, and visual artists Michelangelo
and van Gogh on her list of people whose behavior
might fit the profile of bipolar disorder. Many noted
actors and actresses, including comedian Russell
Brand, Carrie Fisher (Star Wars) (see • Figure 16.17),
and Vivien Leigh (Gone With the Wind), have been
formally diagnosed with bipolar disorder. A con­
trolled study comparing patients with bipolar disorder,
patients with major depressive disorder, and healthy
controls participating in creative or noncreative disci­
plines supports these observations. The patients with
bipolar disorder scored similarly on tests of creativ­
ity to the healthy controls in creative disciplines and
higher than either those with major depressive dis­
order or controls in noncreative disciplines (Santosa
et al., 2007). The parts of the brain that are affected in
bipolar disorder are similar to those seen in cases of
frontotemporal dementia. In both conditions, lower
activity in these areas may reduce inhibition, which
in turn leads to greater creativity (Seeley et al., 2008).
Theories concerning the development of bipolar • Figure 16. 1 7 Is Bipolar Disorder More Common Among
disorder focus on reward sensitivity and disruption Artists? The late Carrie Fisher was one of many creative, artistic
people who have been diagnosed with bipolar disorder.
of circadian rhythms (Alloy, Nusslock, & Boland,
2015). Hypersensitivity to reward could lead to the
excessive approach behaviors, elevated energy, and
decreased need for sleep evidenced by patients with
bipolar disorder. As we observed in Chapter 1 1 , mood and sleep frequently interact,
so it is not surprising that circadian disruptions appear to be an important component
in the development and course of bipolar disorder (Gold & Sylvia, 2016).

Genetics and Bipolar Disorder

Genes play a significant role in bipolar disorder. Concordance rates among identical
twins are as high as 40 to 70 percent (Craddock & Sklar, 2013). Adoption studies also
support a powerful role of genetics in the development of bipolar disorder (Taylor,
Faraone, & Tsuang, 2002). As mentioned previously in this chapter, candidate genes for
bipolar disorder and schizophrenia overlap significantly. Although a number of candi­
date genes for bipolar disorder have been identified, the strength of their effects do not
support genetic testing for vulnerability to bipolar disorder (Craddock & Sklar, 2013).

Brain Structure and Function in Bipolar Disorder

Similar brain structure abnormalities, including reduced gray matter density and cor­
tical thickness, are observed in both schizophrenia and bipolar disorder (Ivleva et al.,
2016). Both conditions are associated with smaller white matter volume, a thinner
parahippocampus, a thinner right orbitofrontal cortex, and thicker temporoparietal
and left superior motor cortices (Hulshoff Pol et al., 20 1 2). These overlapping struc­
tural features are consistent with the shared genetic profiles for these two disorders.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
576 C HAPTER 1 6 Psychopathology

Biochemistry and Treatment of Bipolar Disorder

Bipolar disorder is related to oxidative stress, or an imbalance between the produc­
tion of free radicals and the body's defenses against them (Vasconcelos-Moreno et al.,
2017). In particular, bipolar disorder causes oxidative damage to the DNA of brain
cells, which in turn leads to apoptosis (Soeiro-de-Souza et al., 20 13). Higher amounts
of DNA damage is correlated with the number oflifetime manic episodes.
Lithium salts, a major form of treatment for bipolar disorder, produce antioxidant
effects in animal models of mania (Jornada et al., 201 1) and are likely to produce relief
from symptoms in humans through this same means. Lithium salts also promote adult
neurogenesis in the hippocampus (Quiroz, Machado-Vieira, Zarate, & Manji, 20 10).
The toxicity and unpleasant side effects of lithium salts often lead patients to abandon
the drug. In these cases, other medications available for treating bipolar disorder with
varying levels of success include SSRis, benzodiazepines (e.g., Valium), antipsychotics,
and anticonvulsant mood stabilizers.
Consistent with observations of increased oxidative stress, bipolar disorder features
changes that are consistent with accelerated aging (Rizzo et al., 2014). Similar changes
in inflammation, amyloid, and neurotrophin activity are observed in both patients with
bipolar disorder and individuals with dementia (Rizzo et al., 2014). Individuals with
bipolar disorder experience earlier onset and higher rates of many diseases, including
cardiovascular disease, cancer, and autoimmune diseases (Rizzo et al., 20 14).
Among the environmental factors that interact with candidate genes for bipolar
disorder is diet. Contemporary Western diets are heavy in omega-6 fatty acids and defi­
cient in omega-3 fatty acids, which are essential for the development of the brain and
retina (Simopoulos, 20 1 1 ). Diets high in omega-3 fatty acids, found in fish, might pro­
vide some protection from bipolar disorder (Noaghiul & Hibbeln, 2003). As shown in
• Figure 16.18, prevalence rates for bipolar disorder are highest in countries where fish is
rarely consumed (such as Germany) and lowest in countries where fish is an important

7
0 Germany
• Figure 16.18 Diet May
Influence the Prevalence of
Bipolar Disorder Nations
with heavy seafood consump- 6
tion, such as Iceland, have �
�
lower rates of bipolar disorder
�
than nations where seafood Q) 5
"E
consumption is less typical, 0
C/)
such as Switzerland and 0
Hungary. Omega-3 fatty acids (ij
0 4
have been suggested as a a.

possible protective factor, but i:i5

further research is needed to 0
Q)
(.)
confirm a causal relationship. c: 3
Q)
Source: Noaghiul & Hibbeln (2003). (ii
>
�
Cl..
Q) 2
E
""
.lE
:.:J

lithium A simple salt that appears 50 1 00 1 50 200 250

to stabilize serotonin and
norepinephrine levels in cases of Seafood Consumption (l bs/person/year)
bipolar disorder.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Cengage Leaming. All Rights Reserved. May not be copied. scanned, or duplicated, in wholeor in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.�d con1ent docs no1 macerially affecl the overall learning experience. Ccng:igc Learning reserves the right to remcwe addicion:il contenl at any time if subsequent rights restrictions require it.
 Major Depressive Disorder (MDD) 577

diet staple (such as Iceland). Patients diagnosed with bipolar disorder show reduced
levels of one type of omega-3 fatty acid, DHA (Pomponi et al., 20 13). Administration
of omega-3 supplements reduced the development of psychosis in people at high risk
for psychotic disorders in a randomized, placebo-controlled experiment (Amminger,
Schafer, Papageorgiou, et al., 2010). However, attempts to improve symptoms in patients
with bipolar disorder or depression with omega-3 supplementation have produced
mixed results (Deacon, Kettle, Hayes, Dennis, & Tucci, 2017; Grosso et al., 2014).

Major Depressive Disorder (M OD)

The DSM-5 defines major depressive episodes as periods of pervasive sadness that
last for at least two weeks (APA, 20 1 3). In addition, people with major depressive
disorder (MDD) often withdraw from activities they previously found rewarding,
including hobbies and sex. Major depressive disorder also affects eating habits, energy
levels, sleep, and cognition. People report difficulty concentrating and often experi­
ence thoughts of hopelessness, guilt, worthlessness, and suicide.
MDD affects approximately 7 percent of the adult population each year (APA,
2013). Rates of MDD drop with age, with people in the 18-29-year-old age group
having rates that are three times higher than people over 60 years old.
MDD differs as a function of gender. Prior to adolescence, rates of MDD for boys
and girls are approximately equal. However, rates for boys and girls begin to diverge
between ages 13 and 1 5 (Hankin et al., 1998; Nolen-Hoeksema & Girgus, 1994). As
shown in • Figure 16. 19, adult women are nearly twice as likely as men to be diag­
nosed with MDD (Kessler et al., 2003). This discrepancy between rates of depression in
men and women has been observed independent of demographic factors such as race
and ethnicity, social class, and country of residence (Ustiin, Ayuso-Mateos, Chatterj i,
Mathers, & Murray, 2004), suggesting a biological basis. A number of mood distur­
bances appear to be either caused or made worse by changes in female hormones,
including premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD),
postpartum depression, and mood disturbances experienced by women undergoing
menopause (Rapkin, Mikacich, Moatakef-Imani, & Rasgon, 2002).

major depressive disorder (MDD)

Genetic Contributions to MOD A disorder in which intense
feelings of sadness, hopelessness,
Genes play a moderate role in the development of MDD. Based on analyses of twins,
and worthlessness persist a
the heritability of depression appears to be around 40 percent (Shi et al., 201 1 ). minimum of two weeks.
Adoption studies also support a role for genes in the development of depression (Shih,

14
• Figure 16.19 Age and
Cl> 1 1 .7 • Male Gender Differences in Rates
>
12
"(ii
(/)
• Female of Depression Depression
Cl> 10 becomes less likely with age.
c.
Cl> Women are more likely than
Cl
� Cl> 8 men to be diagnosed with
-� "E
g
depression. Nearly twice
::,?
£ i5 6 as many women as men
§ are diagnosed with major
c 4 depressive disorder.
Cl>
�
Cl>
(L 2

0
1 8-25 26-49 50 or Over
Age in Years

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent does no1 macerially affecl the overall learning experience. Ccng:ige Le:irning reserves the right to remcwe addicion:il contenl at any time if subsequent rights restrictions require it.
578 C HAPTER 16 Psychopathology

Belmonte, & Zandi, 2004). Candidate genes for depression are involved with sero­
tonin reuptake (Wurtman, 2005) and circadian rhythms (McClung, 2007).
Genome-wide association studies have not identified specific single nucleotide
polymorphisms (SNPs; see Chapter 5) correlated with MDD (Shi et al., 20 1 1 ). Efforts
to demonstrate gene-environment interactions between the short version of the sero­
tonin transporter gene and stressful life events have been mixed (Caspi et al., 2003;
Karg, Burmeister, Shedden, & Sen, 20 1 1 ; Smoller, 2016).

Environmental Influences on MOD

As with schizophrenia, prenatal events contribute to MDD. Mothers who were i n their
third trimester of pregnancy during a famine known as the "Dutch Hunger Winter"
of 1944-1945 not only gave birth to more offspring with schizophrenia but were also
more likely to give birth to individuals with MDD (Brown, van Os, Driessens, Hoek,
& Susser, 2000).
Stress often serves as a trigger for depressive episodes (see Chapter 14). Stader
and Hokanson ( 1998) asked participants to list daily stressors, such as having an
argument with a friend. These self-reports were then correlated with the participants'
moods. Depressive episodes were often preceded by significant stressors. Stress
might lead to depression by leading to a larger and prolonged release of cortisol (see
Chapter 14), particularly in people with short versions of the serotonin transporter
gene discussed previously (Gotlib, Joormann, Minor, & Hallmayer, 2008). As we
will see in a later section, cortisol regulation appears to be impaired in some people
with MDD.

Brain Structu re and Function in MOD

Differences between people with MDD and healthy control participants have been
observed in several structures and patterns of brain activity (Wagner et al., 2008).
Reduced volumes in the hippo campus and amygdala along with larger lateral ventricles
have been observed in the brains of patients with MDD (Schmaal et al., 2016). Across
many tasks, lower left frontal lobe activity combined with lower right parietal lobe
activity is associated with depression (Domschke et al., 2016). During decision-making
tasks, patients with MDD showed abnormal activation in the anterior cingulate cortex
(ACC) relative to healthy controls, suggesting that these patients work harder to com­
plete cognitive tasks (Wagner et al., 2008; Workman et al., 2016). Differences in the
volume and activity of these structures in cases of MDD are consistent with the roles
they play in emotional regulation (see Chapter 14).
Correlations between sleep patterns and depressed mood reflect a larger distur­
bance in circadian rhythms (Soria et al., 2010). Both sleeping more than normal (more
than nine hours) and sleeping less than normal (less than seven hours) are symptoms
of depression. As shown in • Figure 16.20, some people who are depressed enter their
first cycle of REM sleep after approximately 45 minutes of sleep rather than the normal
90 minutes. Stages 3 and 4 ofNREM sleep are reduced, and the lighter stages 1 and 2 are
more prominent. Because it is much easier to awaken during REM or during NREM
stages 1 and 2, frequent waking during the night is a common complaint associated
with depression. Sleep deprivation is associated with a significant reduction in depres­
sion (Benedetti et al., 2014; Vogel, 1980). In addition, most antidepressants reduce
REM (Pace-Schott et al., 200 1 ) .
Researchers have debated whether MDD represents a phase advance (Wirz-Justice,
2006) or a phase delay (Robillard et al., 2013). As discussed in Chapter 1 1, a phase
advance occurs when a person sleeps earlier than normal and a phase delay occurs when
a person sleeps later than normal. Depression might result from irregular or missing
circadian rhythms, as opposed to orderly shifts forward or backward (Koenigsberg
et al., 2004; Li et al., 2013).

Copyright 2019 Cengage Learning. A l l Rights Reserved. May not b e copied, scanned, o r duplicated, I n whole o r in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ contcnl at any time if subsequent rights restrictions require ii.
 Major Depressive Disorder (MDD) 579

Typica l person
Awake
REM
& 1
<1l
(ii 2
:2
LU 3
a:
z 4

0 2 3 4 5 6 8
Patient with depression
Awake
REM
�
Ql 1
(ii 2

� 3
a:

t2 t 4
z 4

0 1f 3 t t t 5 6 8

t Pe riods of waking typical

Time (hours)
Awake NREM stage 1 • NREM stage 3
REM sleep • NREM stage 2 • NREM stage 4 for a person with depress ion

• Figure 1 6.20 Depression Is Associated with Abnormal Patterns of Sleep Compared with data from a nondepressed
person, shown in the top row, the depressed person falls asleep much faster, enters REM for the first time much faster, and
spends no time in Stages 3 and 4 NREM. The arrows indicate the typical frequent waking experienced by people with depression.
Source: Adapted from Gillin & Bo rbely (1 985).

Biochemistry of MOD
Abnormalities in monoamine activity, and serotonin activity in particular, are asso­
ciated with depression. A monoamine hypothesis of depression is consistent with
the circadian hypotheses discussed previously because monoamines play essential
roles in the regulation of sleep and waking cycles. As we observed in Chapter 4, the
drug reserpine interferes with the storage of monoamines in vesicles, reducing the
amount of these neurochemicals available for release. Although reserpine has been
used for centuries in Indian folk medicine to treat heart disease, it is rarely used today
due to its ability to produce profound depression (Webster & Koch, 1996). Selective
serotonin reuptake inhibitors (SSRis), frequently used to treat depression, act to
increase the availability of serotonin at the synapse.
In addition to its other duties, serotonin acts as a neurotrophic factor that stimu­
lates both neurogenesis and the release of brain-derived neurotrophic factor (BDNF)
(Moylan, Maes, Wray, & Berk, 20 13). Lower levels of serotonin activity linked with
MDD might result in less neurogenesis. Antiserotonin antibodies are more prevalent
in people with MDD than in healthy controls (Moylan et al., 2013). This autoimmune
response might interfere with serotonin signaling, resulting in the lower levels of sero­
selective serotonin reuptake
tonin activity that accompany MDD. The more depressive episodes a person experi­ inhibitors (SSRI) A type of
ences, the stronger this autoimmune response appears to be, which might account for medication, used to treat major
the recurrent nature of MDD in many patients. depressive disorder and related
conditions, that interferes with
In addition to serotonin abnormalities, altered norepinephrine function is asso­ the reuptake of serotonin at the
ciated with MDD. People who die as a result of suicide show abnormal density and synapse.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from thc cBook andfor eChapler(s).
Editorial review has deemed that any suppres.sed con1cnt docs no1 macerially affecl the overall learning experience. Ccng:ige Le:irning reserves the right to remcwe addicion:il contenl at 311Y time if substtjuent rights restrictions require it.
580 C HAPTER 16 Psychopathology

sensitivity of norepinephrine receptors in the prefrontal cortex (Moylan et al., 20 13).

MDD is associated with reduced axonal density in neurons releasing norepinephrine, a
state that is reversed by the use of antidepressants (Moylan et al., 20 13).
Cortisol is one of several glucocorticoids released by the adrenal glands in response to
both circadian rhythms and stress-related activity in the hypothalamic-pituitary-adrenal
(HPA) axis (see Chapter 14). Because cortisol levels increase in response to stress, this
system provides a link between stressful life events, circadian disruption, and the devel­
opment of depression. Glucocorticoid metabolism is assessed by the dexarnethasone
suppression test (DST). When dexamethasone is injected into healthy participants, cor­
tisol secretion is suppressed. When the test is administered to adults diagnosed with
MDD, about 75 percent fail to show normal cortisol suppression (Aihara et al., 2007).
Following successful treatment, these patients respond normally to the DST.
Patients diagnosed with MDD have lower levels of a major byproduct of dopa­
mine, which suggests that dopamine activity is also reduced in this disorder. It is possi­
ble that repeated stress and the associated release of cortisol and other glucocorticoids
change the responses of the doparninergic reward pathways originating in the midbrain
(Moylan et al., 2013) (see Chapters 4 and 14). The extent of binding of dopamine to
the D2 receptors in the striatum, which includes the nucleus accumbens, distinguishes
between patients who respond well to SSRis and those who do not (Moylan et al., 2013).
Changes in neurochemical activity might be secondary effects of inflammation,
rather than leading causes of depression (Dantzer, O'Connor, Lawson, & Kelley, 20 1 1 ) .
Peripheral inflammatory markers are elevated in patients with inflammatory diseases,
such as asthma, hepatitis, and autoimmune diseases, and in healthy people with MDD.
Inflammation might provide a link between stress and MDD. Stress is associated with
increases in proinflammatory cytokines and decreases in anti-inflammatory cytokines.
Medical application of cytokines to treat diseases such as hepatitis or leukemia can
result in MDD symptoms that are indistinguishable from MDD arising from other
sources (Almond, 2013).

Treatment of MOD
The most common treatment fo r MDD i s antidepressant medication, particularly an
SSRI. Effective antidepressant medications share the ability to stimulate neurogenesis
in the hippocampus (Perera et al., 2007). In animal studies, drugs that block neurogen­
esis also prevent the therapeutic effects of antidepressants (Perera et al., 2007).
SSRis have significant side effects and only about 30-35 percent of patients with
MDD treated with SSRis experience complete remission, leading to the need for alter­
nate or complementary therapies (Trivedi et al., 2006). Exercise produces a moderate
reduction of depression and is a useful addition to other therapies (Blumenthal et al.,
1999; Cooney, Dwan, & Mead, 2014). Cognitive-behavioral therapy (CBT) is as effec­
tive as antidepressant therapy alone. The efficacy of CBT is not affected by the sever­
ity of depressive symptoms, contrary to common clinical guidelines suggesting that
psychotherapy was not indicated for severe depression (Furukawa et al., 20 17).
Electroconvulsive therapy (ECT), illustrated in • Figure 16.21, produces sig­
nificant relief for depressed patients who do not respond to medication or CBT
(Pagnin, de Queiroz, Pini, & Cassano, 2008). In ECT, the patient is anesthetized and
given a muscle relaxant while seizures are induced by electricity applied through
electrodes on the head. Six to 12 treatments are given, typically at a rate of three per
week. Although the exact mode of action for ECT remains unknown, the procedure
affects responsiveness to dopamine and norepinephrine. In addition, like antide­
pressant medications, ECT appears to stimulate neurogenesis in the hippocampus
(Perera et al., 2007). Some patients undergoing the procedure have experienced
electroconvulsive therapy (ECT) amnesia and slower reaction times that persist for six months (Kedzior, Schuchinsky,
A treatment for depression in
Gerkensmeier, & Loo, 2 0 1 7) . Repetitive transcranial magnetic stimulation (rTMS)
which convulsions are produced
by the passage of an electric is emerging as a promising replacement for ECT. Not only has rTMS treatment
current through the brain. (see Chapter 1) reduced depressive symptoms, but some reports show that it also

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02·200-202

Copyright 2019 Cc.ngagc Leaming. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content maybe suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ content at any time if subsequent rights restrictions require ii.
 Major Depressive Disorder (MDD) 581

• Figure 16.21
Electroconvulsive Therapy
(ECT) A patient is shown
being prepared for treat­
ment with ECT for serious
depression. The patient is
given muscle relaxants and
anesthesia before shocks are
applied through electrodes to
induce seizures. The treat­
ments are given over a course
of several weeks.

enhances neurocognition scores rather than decreasing them like ECT (Serafini,
Pompili, Murri, Respino, Ghio, Girardi, et al., 2015).
Patients who do not respond to conventional therapies might benefit from deep
brain stimulation. Stimulating electrodes are surgically implanted in the white matter of
the cingulate cortex ofboth hemispheres, and stimulation is delivered constantly. In one
study, the majority of patients achieved remission of their depressive symptoms after
two years of stimulation (Holtzheimer et al., 2012). Considering that these patients had
been nonresponders to more conventional treatment, this improvement is impressive.

INTERIM S U M MARY 1 6 . 2

11
llllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllltl

Summary Table: Comparison of Positive and Negative Symptoms

of Schizophrenia

Type of Symptom Examples Response to Medication

Positive • Hallucinations Responds to both typical and

• Delusions atypical antipsychotics
• Disorganized speech
• Disorganized behavior

Negative • Mood disturbance Better response to atypical

• Social withdrawal than to typical antipsychotics
• Lack of motivation

11 Summary Points
1. Schizophrenia is a disorder characterized by the presence of hallucinations, delu­
sions, disorganized thinking, social withdrawal, and mood disturbances. (L03)
2. A genetic vulnerabi lity to schizophrenia appears to interact with a variety of environ­
mental factors, including birth complications, prenatal exposure to viruses, marijuana
use, and stress, to produce symptoms of the disorder. (L03)

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent does no1 maccrially affecl the overall learning experience. Ccngage Learning reserves. the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
582 C HAPTER 16 Psychopathology

3. Schizophrenia is usua lly treated with medication, although the addition of psychoso­
cial rehabilitation is quite useful. (L03)
4. Bipolar disorder serves as a "bridge" between the psychotic disorders and depression
and features unrealistically elevated mood states known as mania. Bipolar disorder is
treated primarily with medication. (L04)
5. Major depressive disorder (MDD) is characterized by a constant state of depressed
mood and loss of pleasure in normally enjoyable activities. (L04)
6. Major depressive disorder is treated with medication, cognitive-behavioral therapy, ECT
rTMS, or deep brain stimulation. Increased aerobic activity can be helpful. (L04)

11 Review Questions
1. What are the advantages and disadvantages of the use of medications to treat
schizophrenia?
2. What are the major similarities and differences between schizophrenia, bipolar disor­
der, and major depressive disorder?
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111

Anxiety Disorders
As many as 30 percent of all Americans experience one or more anxiety disorders
during their lifetimes (Kessler et al., 2005). Anxiety disorders take many forms, but all
share the core element of anxiety, a strong negative emotion arising from the anticipa­
tion of danger (Barlow, 1988). We will focus our discussion on panic disorder because
this disorder raises especially interesting and representative biological questions. Before
addressing this specific anxiety disorder, we will explore the biological correlates of this
group of disorders in general.
Twin and adoption studies support a genetic predisposition for anxiety disorders
(Andrews, Steward, Allen, & Henderson, 1990). However, the specific type of anxiety
disorder varies among family members (Dilalla, Kagan, & Reznick, 1994). Anxiety
and MDD share an underlying genetic basis (Smoller, 2016; Weissman, Warner,
Wickramaratne, Moreau, & Olfson, 1997). Nearly two thirds of adult patients with
MDD also meet criteria for at least one anxiety disorder (Mathew, Pettit, Lewinsohn,
Seeley, & Roberts, 20 1 1 ).
Brain structure and activity appear to contribute to the experience of anxiety. We
have seen previously how pathways connecting the brainstem, the amygdala and related
subcortical structures, and the decision-making areas of the frontal lobes are involved
with generating fear in the face of danger (see Chapter 14). Disordered levels of anxi­
ety are often accompanied by distortions in the operation of these pathways. Anxiety
disorders might also involve abnormalities in the HPA axis, resulting in disruptions in
responding to stressful stimuli.
A number of neurochemicals participate in the management of anxiety, includ­
ing serotonin, norepinephrine, and GABA (Taylor, Fricker, Devi, & Gomes, 2005),
and abnormalities in their activity is correlated with anxiety disorders. GABA ago­
nists reduce the subjective experience of anxiety and the activity of the locus coeruleus,
a major source of norepinephrine (Kalueff & Nutt, 2007). Alcohol and benzodiaze­
pines achieve their antianxiety results by enhancing the inhibitory effects of GABA.
Benzodiazepine receptors are particularly common in areas of the brain that partici­
pate in the assessment of potential danger, including the hippocampus, the amygdala,
and the cerebral cortex. Without appropriate levels of GABA-induced inhibition, a per­
son might overreact to perceived threats in the environment.
Treatment for anxiety disorders combines medication with cognitive-behavioral
therapy (CBT). The most commonly prescribed medications include SSRis, serotonin­
norepinephrine reuptake inhibitors (SNRis) (Dell'Osso, Buoli, Baldwin, & Altamura,

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves the rig.ht 10 remove additionaJ contcnl at any time if subsequent righlS restrictions require ii.
 Obsessive-Compulsive Disorder (OCD) 583

2010), and benzodiazepines (Fava, Balon, & Rickels, 2015). Exposure therapy, an appli­
cation of classical conditioning principles, is used to treat many anxiety disorders.
In this process, an individual is exposed gradually to a fear-inducing stimulus until
the fear abates. Virtual reality has made exposure therapy quite easy to administer.
Because not all patients respond to exposure therapy, or respond insufficiently, efforts
are underway to combine medications that enhance the extinction of conditioned fear,
such as D-cycloserine, with exposure therapy (Foa & McLean, 2016).
Anxiety is especially acute in cases of panic. In a panic attack, a person experi­
ences "intense fear or discomfort" accompanied by strong sympathetic arousal leading
to heart palpitations, sweating, trembling, and shortness ofbreath (APA, 20 13, p. 208).
Panic disorder is diagnosed when repeated panic attacks are followed by at least one
month of worrying about having another attack or changing behavior to avoid another
attack. Single panic attacks are relatively common, with one quarter to one third of
college students reporting experiencing one attack in the previous year (Asmundson &
Norton, 1993). Panic disorder is much less common than single panic attacks, affect­
ing between 2 and 3 percent of the population (Kessler et al., 2007). About half of all
patients with panic disorder also suffer from MDD or a second type of anxiety disorder
(Kearney, Albano, Eisen, Allan, & Barlow, 1997).
Panic attacks can be artificially generated in patients suffering from panic disor­
der by administering sodium lactate (Papp et al., 1993). Injections of sodium lactate
decrease central GABA activity while increasing respiratory and autonomic responses
(Johnson et al., 20 1 0). Sodium lactate also provokes panic through its action on orex­
ins in the hypothalamus, which in turn mobilize the sympathetic nervous system for
fight or flight (Johnson et al., 2010). Imaging research suggests that circuits includ­
ing the anterior cingulate cortex, medial prefrontal cortex, and the insula participate
in the panic response (Poletti et al., 2015). These areas process threatening stimuli
(see Chapter 14). Treatment for panic disorder generally consists of either antide­
pressant medication, cognitive-behavioral therapy, or a combination of the two (van
Apeldoorn et al., 2008).

Obsessive-Compu lsive Disorder (OCD)

Individuals with obsessive-compulsive disorder (OCD) are haunted by repetitive, intru­
sive thoughts (obsessions), the need to carry out repetitive behaviors (compulsions)
such as hand washing or counting objects, or both (APA, 2013). Between 2 and 3 percent
of the American public experiences OCD during their lifetimes (Ruscio, Stein, Chiu, & panic attack The experience of
Kessler, 2010). intense feelings of impending
Typical obsessions include thoughts of germs and disease, fear for the safety of doom and the need to escape
accompanied by strong
the self or others, symmetry, and religious or moral concerns. Common compulsions sympathetic arousal, including
include washing, checking, touching, counting, and arranging. Compulsions appear heart palpitations, sweating,
to be efforts to ward off the anxiety produced by the obsessions. For example, peo­ trembling, and shortness of
breath.
ple obsessed with germs and disease often compulsively wash their hands hundreds of panic disorder A condition
times per day. characterized by repeated panic
OCD often features exaggerations of normal behaviors, including the use of rit­ attacks and worries about having
panic attacks.
ual to deal with stress, territoriality, and grooming (Rapoport, 1989). The checking obsessive-compulsive disorder
behavior of patients with OCD, in which a person might check door and window locks (OCD) A disorder characterized
repeatedly, might be an extreme version of the normal presleep routines of our hunt­ by repetitive, intrusive thoughts
and the need to engage in certain
er-gatherer ancestors. The idea that OCD represents exaggerations of natural behavior behaviors to control anxiety.
is supported by observations of similar problems in other species. Dogs occasionally obsession An intrusive thought,
develop an exaggerated grooming version of OCD, in which they repeatedly lick and feeling, or emotion with which
a person is preoccupied;
chew their front paws to the point of causing extensive tissue damage. This behavior characteristic of obsessive­
can be managed with the same medications used to treat OCD in humans (Seksel & compulsive disorder.
Lindeman, 2001). compulsion An irresistible,
repeated impulse to perform an
OCD is characterized by substantial concordance rates (63-87 percent) among action; characteristic of obsessive­
monozygotic twins (Menzies et al., 2008). The rate of OCD in families in which a compulsive disorder.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content maybe suppressed from thc cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ conten1 at any time if subsequent rights restrictions require ii.
584 C HAPTER 1 6 Psychopathology

child has OCD is higher than in families in which only adults have OCD, suggest­
ing that childhood-onset OCD might have separate causal pathways from adult-onset
OCD (Pauls, Abramovitch, Rauch, & Geller, 2014). It is likely that significant gene­
environment interactions occur in OCD (Grisham, Anderson, & Sachdev, 2008).
Symptoms of OCD can arise following head trauma, encephalitis, and seizure dis­
order. Birth complications and streptococcal infections have also been implicated in
the development of OCD in young children (Swedo et al., 1997).
OCD is associated with abnormal patterns of activity in the frontostriatal cir­
cuits implicated in tardive dyskinesia. Once again, the direct pathway facilitates
movement and is inhibited by the indirect pathway (see • Figure 16.22). OCD might

(a) Healthy control

Orbitofrontal Cortex and

Anterior Cingulate Cortex

Striatum f__J Globus Pallidus

Externa

Indirect ­

\
pathway
Globus Pallidus lnterna Subthalamic
Thalamus and Substantia Nigra Nucleus

(b) OCD

Orbitofrontal Cortex and

Anterior Cingulate Cortex

Striatum Globus Pallidus

'-------r--'
Extema
....
_ .____ ___.

I
Globus Pallidus lnterna
and Substantia Nigra

• Figure 16.22 Distortions in Frontostriatal Pathways Characterize OCD Frontal

lobe areas, including the orbitofrontal and a nterior cinculate cortices, form circuits with
the thalamus and basal ganglia that ultimately influence the selection of behaviors.
These images compare the strength of excitatory (green line) and inhibitory (red line)
connections within the circuits. In healthy participants, the effects of an excitatory direct
pathway is balanced by input from an inhibitory indirect pathway. In patients with OCD,
the inhibitory pathway connecting the globus pallidus interna and substantia nigra to the
thalamus is weakened, leading to greater excitation in the pathways between the thala­
mus and the orbitofrontal and anterior cingulate cortices and between these structures
and the striatum. Greater excitatory input to the striatum enhances inhibition of the
globus pallidus i nterna and substantia nigra, further weakening the inhibition of the thal­
amus. The end result of this distortion is an imbalance between the direct and indirect
pathways, resulting in too much activity in the excitatory direct pathway. Behaviors that
might not otherwise be selected will now be performed.
Source: Pauls, D. L., Abra movitch, A., Rauch, S. L., & Geller, D. A. (2014). Obsessive-compulsive disorder:
an integrative genetic and neurobiological perspective. Nature Reviews Neuroscience, 1 5(6), 41 0-424.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 macerially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent righ1s restrictions require it.
 Posttraumatic Stress Disorder (PTSD) 585

result from excessive activity in the direct

pathway (Pauls et al., 2014). Exaggerated
worries about danger, hygiene, or harm,
mediated by the orbitofrontal cortex, might
lead to greater attention to perceived threats
(obsessions) and compulsive behaviors
aimed at reducing threat. The experience of
relief following performance of compulsive
behaviors would reinforce this cycle.
Elevated inflammation in the brains
of patients with OCD, and in frontostriatal
circuits in particular, suggests that OCD
might result from autoimmune processes.
Medications developed to modulate microg­
lial activation in other disorders, such as
Alzheimer's disease, might be useful in the
treatment of OCD. A randomized, dou­
ble-blind, placebo-controlled study of one
of these medications, minocycline, reduced
OCD symptoms when administered along
with an SSRI (Esalatmanesh et al., 20 16).
Imaging studies of brain structure and
function support the frontostriatal model of
OCD. Relative to healthy controls, people
with OCD have increased gray matter in the
basal ganglia and reduced gray matter in the • Figure 1 6.23 OCD and Behavioral Treatment Lewis Baxter and his
cingulate cortices (Radua, van den Heuvel, colleagues (1 992) compared PET scans of patients with OCD both before
Surguladze, & Mataix-Cols, 20 10). Imaging and after either drug treatment or behavioral treatment. In particular,
both types of treatment reduced activity in the caudate nucleus indicated ,
studies indicate that the basal ganglia, orbi­
by the white arrow .

tofrontal cortex, and anterior cingulate cor­

tex are abnormally active in cases of OCD
( Guehl et al., 2008; Pauls et al., 2014; Radua
et al., 2010). Medications that successfully reduce the symptoms of OCD also reduce
the activity of these structures.
OCD is typically treated with antidepressant medications and SSRis in particu­
lar (Soomro, Altman, Rajagopal, & Oakley- Browne, 2008). The most severe cases of
OCD occur in patients with the lowest serotonin levels (Piacentini & Graae, 1997),
making serotonin function a logical target for treatment. As shown in • Figure 16.23,
cognitive-behavioral therapy is effective in cases of OCD, and it produces the same
changes in the basal ganglia as are observed during treatment with medication (Baxter
et al., 1992). However, patients who respond best to SSRis have different patterns of
frontal lobe gray matter than patients who respond best to cognitive-behavioral therapy
(Hoexter et al., 2013). Still other patients experience relief from severe OCD symptoms
with deep brain stimulation of the basal ganglia (de Koning, Fi gee, van den Munckhof,
Schuurman, & Denys, 20 1 1 ).

Posttra u matic Stress Disorder (PTSD)

Posttraumatic stress disorder (PTSD) is the current term for a condition that was
known previously as "shell shock" or "battle fatigue:' Combat experience is a common posttraumatic stress disorder
(PTSD) A disorder arising in
trigger for PTSD, but exposure to natural disasters, accidents, assaults, and abuse can response to an extremely stressful
also result in the disorder (APA, 2013). In PTSD, people exposed to trauma undergo event, characterized by intrusive
"re-experiencing" in the form of recurrent dreams about the traumatic event and memories, recurrent dreams,
avoidance of stimuli associated
unusually vivid and intrusive memories (flashbacks) of the incident. Active avoid­ with the stressful event, and
ance of stimuli associated with the trauma, hyperarousal, high levels of vigilance, and heightened arousal.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from thc cBook andfor eChapler(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 macerially affecl the overall learning experience. Ccng:igc Le:irning reserves the right to remcwc addicion:il contcnl at any time if substtjuent rights restrictions require it.
586 C H APTER 1 6 Psychopathol ogy

persistent negative mood and cognitions are common, leading to frequent impair­
ments in daily functioning (APA, 20 13).
PTSD affects between 3 and 4 percent of American adults in a given year (Kessler
et al., 2007), although more than 12 percent of lower Manhattan residents developed
the disorder as a consequence of the terrorist attacks of 9/ 1 1 (DiGrande et al., 2008).
Twice as many women as men develop PTSD. Children appear more vulnerable than
adults, with 25 percent of children as opposed to 1 5 percent of their parents develop­
ing PTSD following automobile accidents in which they suffer injuries (de Vries et al.,
1999). Combat continues to be one of the most common experiences related to the
development of PTSD. Between 8.5 percent and 14 percent of combat soldiers serv­
ing in Iraq and Afghanistan experienced severe impairment due to PTSD, and up to
31 percent experienced some impairment (Thomas et al., 2010).

Brain Structure and Activity in PTSD

The hippocampus is of interest in PTSD due to the flashback and other memory­
related symptoms of the disorder. Stress-related elevations of circulating gluco­
corticoids, including cortisol, could reduce hippocampal size (Sapolsky, Krey, &
McEwen, 1 985). The effects of extreme stress interact with genetics to predict hip­
pocampal volume. Combat veterans with severe current PTSD symptoms who were
homozygous for the Val l 58Met polymorphism of the catechol-0-methyltransfer-
ase (COMT) gene, which is associated with hippo­
campal volume in healthy controls, had reduced left
hippocampal volume ( Hayes et al., 2017). However,
+ Combat-exposed with PTSD it is unclear whether reduced hippocampal volume
+ Combat-unexposed high-risk co-twins precedes the onset of PTSD, results from PTSD,
+ Combat-exposed twins without PTSD or both.
• Combat-unexposed low-risk co-twins
The anterior cingulate cortex (ACC) has also
12 been implicated in PTSD. The ACC processes emo­
� tional stimuli by regulating attention to emotions and
t::
0 negative states. Changes in ACC structure and func­
8 ••
()
• •
Q)
]1 •• •
tion correlate with alexythymia, a common symptom
::J
Cl 4 • of PTSD featuring deficits in identifying, labeling,
••

-::I;,--
c •• •• •
0
• • or communicating one's emotional state (Demers,
7.-t-
• • •
•
,::.
• • •• Olson, Crowley, Rauch, & Rosso, 20 1 5) . As shown in
�·· :·:
0 0
-�
•

c _L_L_
••
-rtr
••
•
• Figure 16.24, combat-exposed twins with PTSD had
<( lower anterior cingulate cortex volume compared to
-4 • •
0 •
Q) • • their own non-exposed twins and to combat-exposed
E ..
::J
-8
twins without PTSD and their non-exposed co-twins
0
> (Kasai et al., 2008).
I I Compared to veterans without PTSD, veterans
PTSD twin pair Non-PTSD twin pair with PTSD experience higher levels of spontaneous
• Figure 1 6.24 Combat Experience Interacts with activity in the amygdala, anterior cingulate cortex,
Diagnosis of PTSD to Predict Anterior Cingulate Cortex and orbitofrontal cortex, while also experiencing
Volume Lower gray matter volume in people diagnosed with lower levels of spontaneous activity in the prefrontal
PTSD could be either a risk factor for PTSD, a result of PTSD, cortex and thalamus (Yan et al., 2013). The extent of
or both. Vietnam veterans diagnosed with PTSD had lower re-experiencing the traumatic event, or flashbacks,
volume in the anterior cingulate cortex compared to their own was negatively correlated with spontaneous activity
combat-unexposed twins, or combat veterans without PTSD of the thalamus.
and their combat-unexposed twins.
Many of these structural and functional changes
Source: Kasai, K., Yamasue, H., Gilbertson, M. W., Shenton, M. E., interact with prior experience. Childhood trauma
Rauch, S. L., & Pitman, R. K. (2008). Evidence for acquired pregenu­ produces changes in the amygdala and anterior
al anterior cingulate gray matter loss from a twin study of combat­
cingulate cortex that increase a person's vulnerabi­
related posttraumatic stress disorder. Biological Psychiatry, 63(6),
lity to PTSD in response to later exposure to com-
550-556.
bat trauma (Woodward, Kuo, Schaer, Kaloupek, &
Eliez, 2013).

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, o r duplicated, I n whole o r i n part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent does no1 maccrially affecl the overall learning experience. Ccngage Learning reserves. the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
 Antisocial Personal ity Disorder (ASPD) 587

Biochemistry and Treatment of PTSD

Animal research suggests that stress produces a decrease in benzodiazepine recep­
tor binding in the frontal cortex (Fukumitsu, 2002). Similar reductions in benzodi­
azepine activity have been observed in the brains of veterans with combat-related
PTSD (Bremner et al., 2002; Geuze et al., 2008). Because benzodiazepine medica­
tions, such as Valium, have a tranquilizing effect, reductions in benzodiazepine
activity could produce high levels of vigilance characteristic of PTSD.
Treatment for PTSD typically consists of cognitive-behavioral therapy and expo­
sure therapy, with or without antianxiety or antidepressant medication.

Antisocial Persona lity Disorder (ASPD)

Antisocial behavior, or the deliberate harming of others, plagues human societies.
Many perpetrators meet the DSM criteria for antisocial personality disorder (ASPD),
which is characterized by "a pervasive pattern of disregard for and violation of the
rights of others" (APA, 2013 p. 659). People with ASPD are egocentric, lacking empa­
thy, manipulative, deceitful, callous, and hostile. They are irresponsible, impulsive, and
prone to taking unnecessary risks (APA, 2013). Between 0.2 percent and 3.3 percent of
the population experiences ASPD within a given year (APA, 2013). Men are more likely
to demonstrate ASPD than women (Alegria et al., 20 13). Individuals with ASPD often
meet diagnostic criteria for bipolar disorder, major depressive disorder, or substance
use disorders as well (Glenn, Johnson, & Raine, 2013).
ASPD is similar to the concept of psychopathy, although this concept is not
included in the DSM-5. Psychopaths lack guilt, empathy, and normal emotional
responses while callously using others to achieve their personal goals (Hare, 1993). A
triarchic theory of psychopathy argues that three dimensions of disinhibition, bold­
ness, and meanness characterize psychopaths (Patrick, Drislane, & Strickland, 2012;
Patrick, Fowles, & Krueger, 2009).
The DSM-5 places considerable emphasis on criminal and observable behaviors,
rather than focusing on underlying personality traits of manipulativeness, callousne�,
deceitfulness, and impulsivity (Glenn et al., 2013). People with ASPD do not always meet
the definition of psychopathy, and psychopaths and non-psychopaths with ASPD differ in
important ways. For example, psychopaths with ASPD but not non-psychopathic partic­
ipants with ASPD respond differently to threat cues (Drislane, Vaidyanathan, & Patrick,
2013). The non-psychopath participants did not differ from control participants. These
findings suggest that the group of individuals diagnosed with ASPD is heterogeneous.

Genetics and ASPD

Genes explain as much as half the variability in ASPD traits (Rautiainen et al., 2016).
ASPD features complex interactions between genes and environment. In one study, the
extent of child maltreatment, a known risk factor for later antisocial behavior, interacted
with a single gene, MAOA (Caspi et al., 2002). Variations in the MAOA gene had been
implicated in aggression in animal studies. However, variations in the MAOA gene do
not by themselves predict human antisocial behavior (Moffitt, 2005). Instead, variations
in the MAOA gene interact with child maltreatment. Eighty-five percent ofboys with the
antisocial personality disorder
low-activity version of the MAOA gene who experienced severe maltreatment were diag­ (ASPD) A disorder diagnosed
nosed with conduct disorder, a typical precursor condition to ASPD (see • Figure 16.25). in adults, characterized by a
pervasive pattern of disregard
In contrast, boys with the higher activity version of the MAOA gene were not more likely
for and violation of the rights of
to meet criteria for conduct disorder, even when exposed to severe maltreatment. others.
Genes play a larger role in individuals whose antisocial behavior begins in childhood psychopathy A condition
and remains steady during adulthood than in individuals whose antisocial behavior is characterized by an abnormal lack
of remorse and empathy, often
restricted to adolescence (Barnes, Beaver, & Boutwell, 20 1 1 ) . These findings suggest that leading to the exploitation of
environment has more influence on the behavior of adolescence-only offenders. others to meet personal goals.

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content maybe suppressed from thc cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ conten1 at any time if subsequent rights restrictions require ii.
588 C H A PT E R 1 6 Psychopathology

Using assessments that target the emotional aspects

1 00 of psychopathy, as opposed to observations of antisocial
0 No maltreatment behavior, twin studies have indicated substantial heritabil­
• Probable maltreatment ity (46 to 67 percent) for psychopathic traits such as fearless
80
�
�

e.... • Severe maltreatment dominance, impulsive antisociality, and callousness (Blair,

....
Cl)
"E Peschardt, Budhani, Mitchell, & Pine, 2006). Although
0
60
"' child maltreatment appears to interact with genetic predis­
'ti
..
... 40 positions in producing criminal behavior, it is unlikely to
::J
"'C produce the emotional "flattening" that characterizes the
c:
0 psychopath (Blair et al., 2006).
u 20

0
n = 108 42 13 180 79 20
Brain Structure and Function in ASPD
Low MAOA In Chapter 14, we proposed a model in which limbic activa­
High MAOA
activity activity
tion, particularly in the amygdala, provides aggressive drive
• Figure 16.25 G e n es Interact with History of that is normally inhibited by the orbitofrontal cortex and
Maltreatment to Influence Antisocial Behavior Having anterior cingulate cortex. According to this view, impulsive
a low activity or high activity MAOA allele is not predic­ aggression will result from limbic overstimulation, insufficient
tive of antisocial behavior overall. However, male youth frontal inhibition, or both. Not too surprisingly, abnormalities
with the low activity version of MAOA who were also in these structures and their functions have been implicated
subjected to severe child maltreatment were very likely in antisocial behavior. Lower amygdala volume is associated
to be diagnosed with conduct disorder, a childhood
with childhood aggression, early psychopathic traits, and later
disorder that is required for later diagnosis with antisocial
violence in males (Pardini, Erickson, Loeber, & Raine, 2014).
personality disorder. In contrast, male youth with the
high activity version of the MAOA gene who were also One of the most replicated findings in ASPD is reduced
exposed to severe child maltreatment did not differ from volume and activity in the prefrontal cortex (Glenn et al.,
youth who were not abused or those suspected of having 2013). Anderson, Bechara, Damasio, Tranel, and Damasio
been abused in their likelihood of being diagnosed with ( 1999) described two adult participants who had been raised
conduct disorder. in stable, middle-class homes but had experienced damage
Source: Caspi, A., McClay, )., Moffitt, T. E., Mill, )., Martin, )., Craig, to the orbitofrontal cortex before the age of 16 months. As
I. W., et al. (2002). Role of genotype in the cycle of violence in adults, these individuals engaged in stealing, lying, aggres­
maltreated children. Science, 297(5582), 851 -854. sive behavior, poor parenting, and an inability to understand
the consequences of their behavior. Davidson, Putnam, and
Larson (2000) identified frequent orbitofrontal dysfunc­
tions in murderers, people with aggressive impulsive per­
sonality disorder, and people diagnosed with ASPD. Kip Kinkel, who was accused of
murdering his parents and two students in a subsequent school shooting in 1998, was
found to have lesions in his orbitofrontal cortex.
Psychopaths show different patterns of connectivity involving the frontal lobes
when compared to typical control participants (Sundram et al., 2012; Yang et al., 2012).
In addition, the typical controls used the inferior frontal cortices and orbitofrontal cor­
tices as information "hubs;· while the psychopaths used the superior frontal cortices
for this function.
In addition to comparing PET scans of the brains of nonviolent offenders and mur­
derers, Raine, Stoddard, Bihrle, and Buchsbaum ( 1 998) assessed such environmental
factors as neglect, poverty, and physical and sexual abuse. As shown in • Figure 16.26,
the brain activity of the murderers who had experienced abuse and neglect did not
appear different from the brain activity of the normal controls. However, the unabused
murderers show a dramatically reduced level of brain activity, particularly in the frontal
lobes of the brain. As in our previous discussion of heritability of antisocial traits, these
results might reflect differences between psychopaths and nonpsychopathic offenders.
The callousness that characterizes the psychopath might result from diffferent
patterns of brain activity. Criminal psychopaths showed less activity in several limbic
structures than noncriminal controls when exposed to stimuli that normally elicit an
emotional response, such as the word torture (Kiehl et al., 200 1 ) . Criminal psychopaths
were especially impaired in identifying fear in a person's voice (Blair et al., 200 1 ) . These
impairments in empathy, mediated by circuits involving the amygdala and by levels of

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChapter(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 maccrially affecl the overall learning experience. Ccngage Learning reserves. the right to remcwe additional contenl at any time if subsequent rights restrictions require it.
 Antisocial Personality Disorder (ASPD) 589

• Figure 1 6.26 Brain Activity among Murderers Adrian Raine and his colleagues
(1 998) compared PET scans of normal control participants (left), murderers who had a
history of abuse and neglect (middle), and murderers who had not experienced depri­
vation, abuse, or neglect (right). The brain activity of the abused murderers looks quite
similar to that of the normal participants. In contrast, the brain activity of the unabused
murderers is unusually low, especially in the frontal lobes.

oxytocin and vasopressin, could interfere with some of the normal controls that pre­
vent us from hurting one another (Patrick et al., 2012).
Another possible source of interpersonal callousness is deficits in the psychopath's
ability to understand his or her own physical state. Following a task that normally elic­
its an emotional response, nonpsychopathic control participants matched their subjec­
tive verbal description of their physical state to actual measures of heart rate reactivity.
The psychopaths did not show this match (Gao, Raine, & Schug, 2012). As described
in Chapter 14, the James-Lange theory of emotion suggests that assessing our own
physical reactions leads to an understanding of our subjective state. If psychopaths are
unable to do this for their personal emotional experiences, it becomes highly unlikely
that they could assess the states of other people accurately.

Treatment of ASPD
Effective biological treatment approaches for ASPD remain elusive. Existing treatment
programs for violent offenders are frequently based on learning models that empha­
size anger control, social skills, and moral reasoning (Goldstein, Glick, & Gibbs, 1998).
These models have less effect on individuals with psychopathy (Hornsveld, Nij man,
Hollin, & Kraaimaat, 2008).

TH I N KI N G £
ARE PSYCHOPAT HS RESPO N S I B LE FOR THEIR BE HAVIOR?
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111

In Chapter 5, we asked if teens were responsible for

antisocial behavior due to their still developing brains.
What about psychopaths?
the example of placing a beer in front of an alcoholic
and a nonalcoholic. While it is true that the decision to
pick up that beer or not rests with the individual, it is
Adrian Raine (1 999), who conducted some of the also likely that the abilities of these two people to resist
relevant research described in this chapter, sees psycho­ picking up the glass have been shaped differently by
paths' ability to control their actions as lying along a genetic, biological, and environmental influences from
continuum instead of in al l-or-nothing terms. He cites the past.

111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111

Copyright 2019 Cengage Learning. A l l Rights Reserved. May not b e copied, scanned, o r duplicated, I n whole o r in part. WCN 02-200-202

Copyright 2019 Ccngage Le:1ming. All Rights Reserved. May not be copied. scanned, or duplicated, in whole or in part. Due IO electronic rights., some third p:lrty conlcnt m:iy be suppressed from the cBook ::mdfor cChaptcr(s).
Editorial review has deemed that any suppres.sed con1ent docs no1 macerially affecl the overall learning experience. Ccng:ige Learning reserves the right to remcwe additional contenl at any time if subsequent righ1s restrictions require it.
590 C HAPTER 16 Psychopathology

I N T E R I M S U M M A RY 1 6 . 3

11
llllllllllllllllllllllllllllllllllllllllll1111111111111111111111111111111111tllllllllllllllllllllllllllllllllllllllllllllllllllllll

Summary Points
1. Anxiety disorders share a core element of unrealistic and counterproductive anxiety.
In cases of panic disorder, regular panic attacks are accompanied by worry about
further attacks and avoidance of situations associated with attacks. {LOS)
2. Obsessive-compulsive disorder (OCD) combines intrusive, anxiety-producing thoughts
and ritualistic, repetitive behaviors. {LOS)
3. Posttraumatic stress disorder (PTSD) is characterized by i ntrusive flashbacks, hyper­
vigilance, and avoidance of sti muli associated with the experience of trauma. {LOS)
4. Antisocial personality disorder (ASPD) is diagnosed in people who show "a pervasive
pattern of disregard for and violation of the rights of others." {L06)

11 Review Questions
1. What biological changes appear to accompany the experience of anxiety and trauma?
2 . How would you rate the efficacy of treatment methods for ASPD?
111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111111Ulllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllltlllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllllltllllllll

Chapter Review

T H O U G H T Q UESTIONS
1. Why do you think rates of diagnosed autism spectrum disorder and attention
deficit hyperactivity disorder continue to increase?
2. What parallels do you see between major depressive disorder and the anxiety
disorders in terms of genetics, brain structure and function, and biochemistry?
3. Why is bipolar disorder considered to be a "bridge'' between schizophrenia and
major depressive disorder?
4. Which of the disorders discussed in this chapter are influenced by gender? Why do
you think this is the case?

KEY T E R M S
antisocial personality disorder hallucination (p. 566) panic disorder (p. 583)
(ASPD) (p. 587) lithium (p. 576) positive symptom (p. 566)
attention deficit hyperactivity major depressive disorder posttraumatic stress disorder
disorder (ADHD) (p. 563) (MDD) (p. 577) (PTSD) (p. 585)
autism spectrum disorder mania (p. 574) psychopathy (p. 58 7)
(ASD) (p. 558) mental disorder (p. 556) schizophrenia (p. 566)
bipolar disorder (p. 574) negative symptom (p. 566) selective serotonin reuptake inhibitor
compulsion (p. 583) obsession (p. 583) (SSRI) (p. 579)
delusion (p. 566) obsessive-compulsive disorder tardive dyskinesia (p. 573)
electroconvulsive therapy (OCD) (p. 583)
(ECT) (p. 580) panic attack (p. 583)

Copyright 2019 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, In whole or in part. WCN 02-200-202

Copyright 2019 Ccngagc Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the cBook andfor cChaptcr(s).
Editorial review has deemed that any suppressed content docs not materially affect the overall learning experience. Ccngagc Leaming reserves lhc right 10 remove additionaJ contcnl at any time if subsequent rights restrictions require ii.