Psych 2AP3 – Schizophrenia

Schizophrenia Spectrum Disorder & Other psychotic disorders

- Schizotypal personality disorder
- Schizophreniform disorder
- Schizophrenia
- Schizoaffective disorder
- Substance/medication-induced psychotic disorder
- Psychotic disorder due to another medical condition
- Other specified schizophrenia spectrum and other psychotic disorders
- Unspecified schizophrenia spectrum and other psychotic disorders
- Delusional disorder
- Brief psychotic disorder
- Catatonia

DSM-5 Criteria for Schizophrenia

- At least 2 of the following during a 1-month period; 1 must be (1), (2) or (3):
1. Delusions
2. Hallucinations
3. Disorganized speech (frequent derailment or incoherence)
o Disorganized catatonic behaviour
o Negative symptoms
- For much of the time, level of functioning in one or more areas is below that achieved
before onset of symptoms
- Signs of disturbance persist for at least 6 months, including 1 month of symptoms from
list
- Schizoaffective disorder and depressive or bipolar disorder with psychotic features have
been ruled out
- Disturbance not due to effects of a substance or to another medical condition

Symptoms of Schizophrenia
- Disorders in form or content of thought
o Form of thought
 Loosening of associations
 Poverty of speech content
 Vagueness, abstraction in speech
 Neologisms, clanging, perseveration
o Content of though: implausible delusions
 Of persecution, reference
 Thought manipulation:
 Thought insertion
 Thought withdrawal
 Thought broadcast
  External control
Symptoms of Schizophrenia
- Disorders of perception – Hallucinations
o Auditory:
 Voices outside the head
 Criticizing or commenting on behaviour
 Repeating individuals thoughts
 Commanding individuals to act
o Tactile
 E.g tingling, burning sensations
o Somatic
 E.g snakes crawling in abdomen

- Flat or inappropriate affect

- Disturbance to sense of self
o Unclear sense of identity, outside control
- Avolition
o Loss of interest, will, ambivalence
- Impaired interpersonal functioning
o Social withdrawal, emotional detachment
- Psychomotor behaviour (catatonia)
o Stupor: “cerea flexibilitas’
o Excitement

Symptom Frequency
- Lack of insight – 94%
- Blunted affect – 82%
- A sociality – 79%
- Delusions – 73%
- Autism – 72%
- Apathy – 60%
- Thought derailment 58%
- Suspiciousness – 51%

Positive vs Negative Symptoms

- Positive symptoms:
o Disturbance, excess of normal function
 Hallucinations
 Delusions
- Negative symptoms
o Diminution, loss of normal function
 Alogia: poverty of speech
 Flat affect
  Anhedonia – asociality
 Avolition
Course of Schizophrenia
- One episode, full remission: 25% of cases
- Episodic, partial remission: 25% of cases
- Episodic, full remission: 20% of cases
- Episodic, becoming chronic: 15% of cases
- Chronic deterioration: 15% of cases

Epidemiology
- Point prevalence
o U.S. & Canada: 50-70/10000
- Lifetime prevalence
o U.S. & Canada: 100-190/10000
o U.S. & Canada:: 150/10000
- Onset in adolescence, early adulthood
o Usually diagnosed 18-35 years
- More males than females:
o 1.0/1.0-2.0/1.0 male female ratio

Etiology: Brain Structure

- Enlargement of cerebral ventricles:
o Proportion of patients varies widely (6-60%)
o Perhaps older patients only
o Enlargement associated with:
 Poor premorbid functioning
 Age and/or chronicity
 Negative symptoms
 Cognitive impairment
 Poor response to treatment
 History of birth complications
 Lack of familial psychiatric history
- Reduced brain asymmetry
o More ambidexterity and sinistrality
- Reduced brain size on MRI:
o Smaller frontal lobes, cranium
o Suggests prenatal, perinatal injury
- Cell atrophy or loss:
o Hippocampus, limbic system, periventricular areas

Etiology: Brain Activity

- Hypo frontality:
o Controls higher in frontal, lower in posterior; reversed in schizophrenia
 - Abnormal EEG
o More beta activity in left temporal areas
o More variability in left temporal lobes
o More delta waves in frontal lobe
- ERP (P300 wave)
o Lower in schizophrenia
o No change with prediction, or with incentives for speed or accuracy

Etiology: Viral Agents?

- Winter births:
o 15% more births in winter months
o Especially in cities, where infection risk high
- Viral infection CNS abnormalities
- Viruses more common in winter: Rubella, measles, flu
- More virus antibodies in patients
- Elevated interleukin-1beta; immune system response to inflammation ( Soderlin et al)

Etiology: Dopamine Hypothesis

- Hyperactivity of dopamine
- Neuroleptic drug effects:
o Effective drugs (phenothiazines) block dopamine receptors in animals
 Not all patients respond to phenothiazines
 Phenothiazines work in mania, other psychoses
 Effect may be indirect
- Dopamine antagonists reduce symptoms
- Dopamine agonists produce symptoms
o Amphetamine overdoes mimics paranoid schizophrenia

Problems with Dopamine Hypothesis

- Van Kammen et al (1981) reviewed 12 studies of amphetamine administration:
o 25% of patients worsened
o 46% of patients unchanged
o 28% of patients improved
- MAO inhibitors do not worsen schizophrenic symptoms (Brenner & Shopsin, 1980)
o 3% of patients worsened
o 71% of patients unchanged
o 26% of patients improved

Etiology: Types I and II

- Type I: Excess dopaminergic activity
o Positive symptoms predominate
o Usually acute, good prognosis
o No structural brain damage
 o Neuroleptics effective in treatment
- Type II: Neuron loss?
o Negative symptoms predominate
o Intellectual impairment
o Poor prognosis

Dopamine Receptors & Schizophrenia

- Perhaps dopamine receptors, not amount?
o Two receptor types: D1,D2
o Effective drugs block D2 more than D1
- Crow et al (1982)
o Compared alpha-, beta-flupentixol on schizophrenia symptoms
o Alpha-blocks D2 receptors predominantly
 Reduces positive, not negative symptoms
o Beta- unspecific blocker of receptors
 No reduction in symptoms; same effect as placebo

Etiology: Genetic – Twins

Kringlen (1967): MZ = 45%; DZ=15%
Pollin et al (1969): MZ = 43%; DZ= 9%
Gottesman (1972): MZ= 58%; DZ=12%
Fischer (1973): MZ=56%; DZ= 26%
Gottesman (1982): MZ = 46%; DZ= 14%

Etiology: Genetic-Family
- Child (both parents affected) = 46%
- Child (one parent, one sib affected) = 17%
- Child ( one parent affected) =12%
- Children (one sib affected) =10%
- Grandchild (one grandparent affected) = 4%
- Uncle/aunt/niece/nephew = 3%

Etiology: Chromosomal Regions

- Chromosomal regions
o 1p21-22, 6p24-22, 13q32-34, 1q42, 5q21-33, 6q21-25, 10p11-15, 22q11-12, 8p21

Etiology: Specific Genes

 - “ attempts to locate and identify genes have proved to be difficult. This is largely
because major genes appear to be rare or nonexistent. Instead, genetic liability almost
certainly results from the combined effects of multiple susceptibility loci”

Schizophrenia Genes & Other disorders

Smoller et al (2014)
- Studied SNPs in large Genome-wide association study (GWAS)
- Found shared genetic risk among five major clinical disorder categories:
o Schizophrenia
o Major depression
o Bipolar disorder
o Autism spectrum disorder
o Attention deficit/hyperactivity disorder

Copy Number Variations (CNV)

- Recent interest in CNVs rather than single nucleotide polymorphisms (SNPs)
- Perhaps rare uncommon CNVs involved
- Perhaps the high number rather than the location of CNVs that is involved in
schizophrenia
- Specific areas of interest:
1q21.1;3q29;7q36.3;15q11.2;15q13.1;15q13.3;16p11.2;22q11.2

Treatment Approaches
- Antipsychotic medication
o Tardive dyskinesia: repetitive, involuntary movements
- Electroconvulsive Therapy (ECT)
o 17% of ECT patients have schizophrenia
o Not as effective as antipsychotics in chronic cases
o Not effective in acute cases
o Primarily for catatonia, where depression involved, an for those not responding
to antipsychotics
- Individual psychotherapy
 o Ineffective chronic cases
o Helps develop new coping strategies
- Group psychotherapy
o Provides social support
o Helps develop social skills
- Family therapy
o Focuses on more emotional families
o Helps prevent relapse

Metalessons?
- Causes of mental disorders unknown:
o Similar symptoms may have different causes
o Similar causes may lead to different symptoms
- Causation is complicated:
o Neurochemistry and genetics affect behaviour
o Behaviour and experiences affect neurochemistry and genetic expression
- Field fact-filled, but understanding poor
o We know much, understand little
o Ignorance, uncertainty, contradiction and confusion are the price of knowledge