Curr Obes Rep

DOI 10.1007/s13679-015-0164-9

HEALTH SERVICES AND PROGRAMS (SFL KIRK, SECTION EDITOR)

An Overview of Links Between Obesity and Mental Health

# Springer Science+Business Media New York 2015

Abstract The American Medical Association recently recog- population [1–4] and is best conceptualized as a complex,
nized obesity as both an illness and a leading cause of pre- multifactorial disorder with both genetic and environmental
ventable death and chronic disease. This association is not components [1]. It is associated with increased mortality
only linked to physical health outcomes, however, as obesity and comorbidities, such as hypertension, dyslipidemia, di-
has also been extensively associated with mental illness as abetes mellitus, coronary heart disease, congestive heart
well. Both obesity and severe mental illness decrease quality failure, stroke, gallstones, osteoarthritis, sleep apnea, and
of life and are associated with an increase in disability, mor- certain types of cancer, impaired fertility, and increased
bidity, and mortality, and when they occur together, these ad- pregnancy risks [5]. It is not surprising; therefore, that obe-
verse health outcomes are magnified. Despite educational sity is the fifth leading cause of death worldwide [6].
campaigns, increased awareness, and improved treatment op- Obesity also imposes a heavy financial burden on society.
tions, the high prevalence of mental illness and comorbid obe- In the United States it is estimated that the total health care
sity remains a serious problem. This review examines this costs attributable to patients with obesity or who are over-
overlap, highlighting clinical and biological factors that have weight will double every decade to reach $860.7–956.9
been linked to this association in order to improve our under- billion by 2030, accounting for 16–18 % of the total US
standing and help elucidate potential therapeutic avenues. health care costs [7]. Similarly, mental illnesses, broadly
categorized as disorders characterized by dysregulation of
Keywords Obesity . Mental health . Pharmacological mood, thought, and/or behavior [8], are also associated with
treatment . Genetic and environmental factors considerable disease burden. Indeed, the Global Burden of
Disease Study 2010 (GBD 2010) ranked mental and sub-
stance use disorders as the fifth leading contributor of bur-
den as measured by disability adjusted life years (DALYs)
Introduction
[9]. Mental illnesses are highly prevalent in North America;
in 2012, it was estimated that 43.7 million adults aged 18 or
Obesity, defined as a body mass index (BMI) greater than
older in the USA suffered from mental illness, representing
30 kg/m 2 , affects up to 30 % of the North American
18.6 % of the adult population [10].
This article is part of the Topical Collection on Health Services and Obesity and mental illness are each prevalent chronic
Programs conditions, but there is evidence that the two may be
associated [11], and that their co-occurrence is more than
* Valerie H. Taylor an expected spurious overlap of two commonly existing
valerie.taylor@wchospital.ca conditions. However, the mechanisms linking obesity and
mental illnesses are unclear. This paper provides an over-
1
McMaster University, 1280 Main Street West, HSC 3N52A, view of current evidence on the association between obe-
Hamilton, ON L8S 4K1, Canada sity and mental illness, the possible pathophysiological
2
Department of Psychiatry, University of Toronto, 76 Grenville Street, mechanisms involved in the association, and novel emerg-
Toronto, ON M5S 1B2, Canada ing therapeutic options.
 Curr Obes Rep

Association Between Obesity and Mental Disorders [18]. Part of this association is thought to be due to the obser-
vation that individuals with ADHD display an inability to
The first reports regarding the increased risk of obesity in organize meals, often eat impulsively [18, 19•], and are less
patients with mental diseases were documented in 1946 when engaged in physical activity and organized sports [20].
Nicholson reported emotional tension and psychoneurosis School-aged children with ADHD are also more likely to have
factors to be associated with obesity [12]. Since that time, poor physical fitness, delayed motor development [19•, 21],
there has been a large amount of research examining the links and display more negative feelings about physical activity
between these clinical areas, and a common theme emerging [19•, 22]. Almost 60 % of individuals with ADHD will con-
from this work is a bidirectional association between obesity tinue to have symptoms into adulthood [23], and the associa-
and mental health [13]. Individuals with a mental illness have tion between the illness and obesity increases in prevalence
a 2- to 3-fold increased risk of obesity, and the risk of mental with age, again due in part to issues with organization and
illness in individuals with obesity has been documented to impulsivity.
range between 30 and 70 % [14]. Obesity has been associated The biological underpinnings of this association are not
with a number of psychiatric disorders, including a lifetime well understood but one hypothesis is that ADHD (predomi-
history of mood disorders, anxiety, personality disorders, at- nantly with deficit of attention), and obesity may reflect dif-
tention deficit hyperactivity disorder (ADHD), binge eating ferent manifestations of a single and hypofunctional dopamine
disorder, trauma, and schizophrenia, and it is also a side effect gene variant (the 7-repeat allele of DRD4) [19•]. Levitan et al.
of many of the drugs used to treat mental illness [15]. In the [24] examined the possible contribution of 7R to the overall
following paragraphs, we will discuss the most common men- expression of attention deficit disorder (ADD) and body
tal disorders associated with obesity and factors hypothesized weight regulation. The 7R allele of DRD4 may be associated
to explain some of the association. with a unique developmental trajectory characterized by atten-
Figure 1 summarizes the bidirectional relationship between tional deficits and dysphoria in childhood and mild to moder-
obesity and mental illnesses and the factors contributing to the ate obesity in adulthood [24]. A related hypothesis is that
association. people with low intrinsic dopamine activity in the areas of
the brain that mediate reward may attempt to compensate by
Obesity and ADHD using various reinforcing behaviors, including increased food
consumption [25]. Therefore, patients with obesity with ab-
ADHD is one of the most common childhood psychiatric normal eating behaviors and ADHD may present with com-
disorders, affecting 5–10 % of school-aged children [16]. mon genetically determined dysfunctions in the dopaminergic
Interestingly, non-medicated children diagnosed with ADHD system [23]. Since binge eating behaviors may be present in
have a 1.5-fold increased risk of becoming overweight relative patients with obesity (especially in those with severe obesity)
to control subjects [17]. Studies have also revealed high rates [26], it is possible that impulsivity associated with these ab-
of ADHD in patients seeking weight loss treatment (26– normal eating behaviors may be part of an ADHD impulsivity
61 %), suggesting an association between ADHD and obesity spectrum [27]. These symptoms may also pose a potential

Fig. 1 Bidirectional
interrelationship between obesity
and mental disorders
Curr Obes Rep

barrier to the treatment of obesity in patients with ADHD as responses to trauma-related stimuli have all been found in
they impact the basic tenets of obesity management (i.e., eat- adults diagnosed with PTSD [40]. An elevated waist circum-
ing in a thoughtful organized manner and engaging in regular ference is also linked to increased cortisol, a stress hormone
physical activity). This is supported by evidence that suggests that is elevated in both acute and chronic stress [41]. Animal
that subjects participating in weight loss programs who re- studies suggest that stress upregulates neuropeptide Y (NPY)
ceived treatment for their ADHD diagnosis typically lost which plays an important role in adipose tissue remodeling
12 % of their initial weight as compared to controls [19•]. and development of abdominal obesity [31, 42]. Thus, high
This effect was seen not only in participants receiving stimu- levels of stress may directly alter fat production and its distri-
lant treatment, but also in those receiving non-stimulant phar- bution. Food addiction prevalence appeared to be further ele-
macotherapy, indicating that the effect was more than drug- vated when PTSD symptoms occurred earlier in life [43].
induced appetite suppression and related, at least in part, to Thus, in the last decades, PTSD has emerged as a risk factor
changes in neurobiology [19•, 28]. for obesity and metabolic dysfunction.

Obesity and PTSD Obesity and Mood Disorders

Post-traumatic stress disorder (PTSD) is known to develop in Major depressive disorders (MDD) and bipolar disorder (BD)
the aftermath of a traumatic event characterized by exposure are illnesses characterized by a symptom profile that can im-
to actual or threatened death, serious injury, or sexual violence pact appetite, energy, sleep, and motivation [19•]. As a conse-
[29]. In a recent large study, [30] 60 % of women and 33 % of quence, it is not surprising that most studies examining weight
men with obesity identified PTSD as a contributing factor. change in this population document increases over time. The
PTSD symptom onset appears to alter BMI trajectory over prevalence of obesity was almost 2-fold higher in patients
time and is associated with increased risk of overweight or with MDD and BD versus the general population [44].
obesity [30, 31]. For instance, in a study of nearly 500,000 Obesity is one of the most prevalent somatic comorbidities
war veterans [32•], the authors found that during the 3-year of MDD, and both conditions rank among the leading chal-
ascertainment period, those with PTSD and depression were at lenges in public health [45, 46]. Similarly, individuals with
greatest risk of being overweight or obese or were continuing BD also have been shown to have an increased waist/hip ratio
to gain weight. This association also appears to have a gender and are more likely to be classified as being centrally obese
effect. In women, obesity was associated with symptoms of compared to people without BD [47]. Exactly how these co-
serious psychological distress (SPD), PTSD, and depression, morbidities influence each other is unknown, but there is some
while in men, it was associated with symptoms of generalized evidence that, at least in adults, psychiatric symptoms often
anxiety disorder and SPD [33]. The prevalence of metabolic emerge first [48].
syndrome was also higher in patients with PTSD as well as the The mechanisms involved in the association between mood
prevalence of its individual components, which strengths the disorders and obesity have been extensively studied, and [49]
association [34]. Early life trauma can also confer an increased it appears that many aspects of the neurobiology of depression
vulnerability to obesity [35], with evidence suggesting that also confer an increased risk of obesity. The changes of hypo-
more severe forms of abuse, or abuse that occurs more fre- thalamic pituitary adrenal (HPA) axis seen in depression are
quently, are more likely to result in higher BMIs [36]. similar, although less extreme, to those seen in Cushing syn-
A number of explanations have been postulated to under- drome, an endocrine illness characterized phenotypically by
stand the link between obesity and trauma [31]. From a be- excessive visceral weight gain [19•], indicating that dysregu-
havioral perspective, trauma may be linked to the use of food lated cortisol is a player in both mood and weight regulation
as a coping strategy and as a method of self-soothing [37]. [50, 51]. The role of inflammation has also been investigated,
Eating can therefore result in a temporarily elevated mood and and there is a compelling body of evidence supporting the fact
can create a behavioral cycle where food is consumed to con- that obesity, MDD, and BD represent conditions associated
trol feelings of sadness [19•], as is evidenced by work focused with chronic low-grade inflammation [11, 52–55]. Elevated
on the role of serotonin and dopamine playing a critical role in levels of inflammatory markers such as tumor necrosis factor
eating behavior and mood regulation [38]. Recent studies (TNF) alpha, C-reactive protein, and inflammatory cytokines
have also suggested PTSD is associated with physical inactiv- such as interleukin (IL)-1, IL-2, and IL-10 are seen in MDD,
ity [39], increased consumption of unhealthy foods and bev- BD, and obesity [52]. Adiponectin has been implicated as a
erages [40], or generally dysregulated food intake related to mediating factor between obesity and depression [53] through
dependence on activation of the brain reward system [31]. In induction of anti-inflammatory cytokines such as IL-10 and
addition, dysregulated neuroendocrine function, including en- antagonism of the IL-1 receptor in human monocytes macro-
hanced negative feedback sensitivity of glucocorticoid recep- phages and dendritic cells [54]. Serum levels of adiponectin
tors, blunted cortisol levels, and exaggerated catecholamine are markedly decreased in individuals with visceral obesity
 Curr Obes Rep

[55], and the effects of adiponectin are inhibited by glucocor- weight gain compared to chronically ill patients [72].
ticoids. [55, 56] Obesity is associated with altered levels of the Interestingly, before the diagnosis, patients with schizophrenia
adipokines, favoring an increase in leptin and resistin, a de- often have a lower BMI than control subjects [73], but over
crease in adiponectin, and alterations in levels of cortisol. The time, the reported prevalence of overweight and obesity in
changes in these biomarkers are more difficult to quantify in patients with psychotic spectrum disorders has been found to
patients with MDD, but an emerging body of evidence sug- range from 40 to 62 % [74], lending support to the notion that
gests that further investigation is warranted to describe the treatment contributes to weight increases. Other factors com-
links between obesity, depression, and adipokine levels [56]. monly implicated in the development of obesity in persons
Evidence from epidemiologic studies and meta-analysis [57] with schizophrenia include sedentary lifestyle, lack of exer-
also support the idea of an overlap between obesity and mood cise, and poor dietary choices. The mechanisms underlying
disorders. Longitudinal studies confirm that depression in ad- the association between schizophrenia and obesity are com-
olescence is a significant predictor of elevated body mass plex, and pathways remain to be elucidated. Antipsychotics
index (BMI) in adulthood, and individuals with obesity are bind a wide range of receptors affecting a range of neurotrans-
also more likely to report a major depressive episode com- mitters involved in energy homeostasis [75]. Several modera-
pared to individuals considered a healthy weight [58]. An tors and mediators for weight gain during antipsychotic treat-
important mediator of the association between depression, ment have been reported including patients factors such as
BD, and obesity is pharmacotherapy [59], which can often age, BMI, and gender, illness related factors (treatment naive,
lead to sedation and increased appetite affecting both physical extent of symptom reduction, etc.), and treatment variables
health and treatment adherence [60]. Furthermore, weight related to duration, dose, and drug type [75]. Furthermore,
gain and its associated medical comorbidities may reduce patients exposed to most antipsychotics have greater appetite
the likelihood of positive clinical responses to pharmacologic and eat more but the composition of their food is not neces-
therapies [60]. The previous highlight the importance of prop- sarily altered on medication. In addition to increased appetite,
er weight gain management in this specific population with delayed or dampened satiety signaling has also been observed
concomitant mood disorders. and proposed as a mechanism for weight gain [76].
Neurohormonal changes were also demonstrated in schizo-
Obesity and Schizophrenia phrenic patients treated with second-generation antipsychotics
(SGAs). Accumulating evidence support the notion that
Schizophrenia (SCZ) is a debilitating illness present in ap- peripherical metabolic hormones (such as leptin from the ad-
proximately 1 % of the global population and characterized ipose tissue and gut ghrelin) could play a role on alterations in
by a combination of psychosis, impairments in cognition, and regulation of food intake and energy balance in patients with
negative symptoms [61]. It is also often accompanied by high schizophrenia [77]. Furthermore, leptin, the anorexigenic sig-
rates of numerous physical diseases including diabetes, car- nal from the adipocytes, acts through its receptors by activat-
diovascular diseases, deep vein thrombosis, and pulmonary ing hypothalamic melanocortin neurons which in turn produce
embolism [62, 63]. The standardized mortality ratio for death the anorexigenic hormone alpha melanocyte stimulating hor-
from cardiovascular disease is doubled in schizophrenia as mone [77]. Moreover, the 5-hidroxytryptamine (5-HT)-driven
compared to the general population, and those with this illness dysregulation of melanocortin system appears to be signifi-
have a lifespan that is shortened by as much as 25 %, inde- cantly involved in second-generation antipsychotics induced
pendent of suicide risk [64, 65]. It is generally recognized that obesity and diabetes [74]. Serotonine affects energy homeo-
the cardiometabolic profile, high rates of obesity, and in- stasis by stimulating melanocortin neurons through 5-HT2C
creased cardiovascular (CV) risk in this population is due to receptors [78]. Antagonism at this serotonin receptor increases
a composite of inherent biological risk associated with SCZ appetite, which might explain the antipsychotic treatment-
itself [66], illness-associated lifestyle effects [67], and meta- induced weight gain [78]. Second-generation antipsychotics
bolic side effects of the newer atypical antipsychotics (AAPs) have also been hypothesized to induce weight gain by differ-
[68]. Introduction of AAPs, now the mainstay of treatment, ent mechanisms: (1) contributing to decreased energy expen-
has not only been linked to distinct benefits [69] but also diture; (2) enhancing the opioidergic activity which could fur-
significant concerns related to increased liability for serious ther deteriorate the preexisting hedonic alterations in schizo-
metabolic changes, including weight gain, dyslipidemia, and phrenia patients [79]; (3) altering the function of lateral hypo-
type 2 diabetes (DM2). While a differential metabolic liability thalamic serotonin and/or histamine medidated actions [80];
exists between the available AAPs (clozapine = olanzapine > (4) inducing dopamine antagonists; (5) altering glucose up-
risperidone = quetiapine > aripiprazole = ziprasidone), those take by blocking glucose accumulation directly at the level of
early in the illness are vulnerable to antipsychotic-induced the glucose transporter (GLUT) protein in cells derived from
weight gain regardless of the metabolic liability of agent used both peripheral and brain tissue [81]; (6) inducing insulin re-
[70, 71], with a 3–4-fold larger magnitude of AAP-related sistance and impairments in insulin secretion directly [82, 83],
Curr Obes Rep

and (7) promoting triglyceride accumulation by stimulating bariatric surgery, downregulation of the dopamine D2 recep-
lipogenesis and inhibiting lipolysis [74]. Second-generation tors linked to addictive behavior has been reported.
antipsychotics also target the deregulated HPA axis. HPA axis Endogenous opiates, another group of players in the reward
has a major role in allocating glucose to the brain, and accord- pathway, are also activated by drugs and by food, in particular
ing to this theory, less active HPA axis will inadequately sup- to sweet foods. Conversely, the opioid blocker naltrexone has
ply the brain with energy sources so at the hypothalamic level been shown to reduce cravings for both substances of abuse
compensatory increase in food intake will occur. and food. Compounds that act as inverse agonists within the
Evidence has also shown an increase of abnormal glucose endocannabinoid system have also been used both to treat
metabolism, diabetes, and impaired glucose tolerance in drug- substance addictions and to promote weight loss [26].
naive schizophrenic patients, indicating that the iatrogenic Furthermore, it is possible that at least a subset of obese indi-
weight gain associated with medication use is not the only viduals may suffer from a psychiatric disorder that makes it
factor involved [84•, 85]. For instance, almost 60 % of people particularly difficult for them to limit food consumption, just
treated for the first episode of psychosis has metabolic syn- as it is difficult for individuals with alcohol or drug depen-
drome [86], which was proposed to be more frequent than in dence to limit consumption of those substances [51]. Some of
the patients treated with first-generation antipsychotics (APs) the differences between overeating and substance dependence
[74]. Increased leptin has been reported in AP-naive people may have implications for future definitions of substance use
with schizophrenia although the mechanism still needs to be disorders.
elucidated [87]. Others factors can contribute to the increased
weight gain in schizophrenia such as amotivation, high rates Obesity and Binge Disorders
of substance abuse (cannabis), aberrations in cortisol produc-
tion, and even comorbid depression [88]. Binge eating disorder (BED) is characterized by recurrent ep-
isodes of binge eating in the absence of regular use of inap-
Obesity and Substance Abuse propriate compensatory behaviors characteristic of bulimia
nervosa [91–95]. Approximately 30 % of patients seeking
Substance abuse has been defined as a compulsive pattern of treatment for obesity will meet the diagnostic criteria for
substance use, even in the face of negative health and social BED whereas the prevalence of BED in general population
consequences [89]. Both food and drugs induce tolerance over is approximately 2.5 % [92]. BED has been associated with
time, whereby increasing amounts are needed to reach and reduced activity in the orbitofrontal and prefrontal cortex
maintain intoxication or satiety. In addition, withdrawal symp- areas, as well as dysfunctional dopaminergic and opioid path-
toms, such as distress and dysphoria, often occur upon discon- ways, changes that have been linked with behavioral impul-
tinuation of the drug or during dieting [89]. In vulnerable sivity [96]. Hence, binge eaters without compensatory behav-
individuals (through genetic liability or other individual fac- iors may avoid recognition and more frequently delay seeking
tors), reinforcers in the form of food or drugs become professional help [97]. The majority of obese people with
overvalued relative to other reinforcers as a result of condi- BED do not recognize they have disordered eating that has a
tioned learning [90]. Then, an elevated expected or anticipated neurobiological explanation and refrain from seeking help.
reward overactivates memory and reward circuits and inhibits Psychiatric symptoms such as mood and anxiety disorders,
cognitive control circuitry, which in turn, leads to an inability which are often comorbid with BED, are more common pre-
to self-manage the drive to consume drugs or foods [91]. senting complaints in this population as they are often comor-
Epidemiological studies examining relationships between bid with BED, further increasing the risk of weight gain for
obesity and substance use disorders yield ambiguous results reasons described previously. The US Food and Drug
[51]. For example, moderate alcohol consumption is some- Administration (FDA) approved uses of lisdexamfetamine
times associated with increased BMI [92]. Petry et al. [93] dimesylate, a central nervous system stimulant previously
found higher lifetime rates of alcohol use disorders with in- used to treat ADHD to treat binge eating disorder in adults,
creasing BMI starting in the overweight range and increasing again illustrating the complicated and overlapping associ-
across BMI categories. However, the effect of alcohol on ations between mental illness and weight gain (www.fda.
weight gain could also be explained by the additional calories gov/newsevents/newsroom/pressannouncements/
intake (7 kcal/g), associated to a lack of effect on satiety [94]. ucm432543.htm).
Different mechanisms have been proposed to explain the
association between obesity and substance abuse. Imaging
studies have shown that specific areas of the mesolimbic sys- Conclusions
tem, such as the caudate nucleus, the hippocampus, and the
insula, are activated both by substances of abuse and by food There is a well-established bidirectional relationship between
[26]. Conversely, following treatment of obesity by means of obesity and psychopathology. Obesity has been associated
 Curr Obes Rep

with a number of psychiatric disorders, including mood dis- Health Services Administration; 2013. http://store.samhsa.gov/
home.
orders, anxiety, personality disorders, and schizophrenia, and
11. Kivimäki M, Batty GD, Singh-Manoux A, et al. Association be-
the factors involved in the association are varied and complex. tween common mental disorder and obesity over the adult life
It is important however for policy makers to understand some course. Br J Psychiatry. 2009;195(2):149–55.
of these underpinnings in order to ensure that we decrease 12. Nicholson WM. Emotional factors in obesity. Am J Med Sci.
burden of illness in this vulnerable population. 1946;211:443–7.
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relationship between obesity and health-related quality of life: evi-
Compliance with Ethics Guidelines dence from the longitudinal AusDiab study. Int J Obes (Lond).
2012;36(2):295–303.
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interest. with severe mental disorders. I. Prevalence, impact of medications
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Margaret K. Hahn declares that she has no conflict of interest. 15. Remington G. Schizophrenia, antipsychotics, and the metabolic
Katherine M. Morrison declares that she has no conflict of interest. syndrome: is there a silver lining? Am J Psychiatry. 2006;163(7):
Maria Restivo declares that she has no conflict of interest. 1132–4.
Rebecca Anglin declares that she has no conflict of interest. 16. National Institute of Mental Health (NIMH). Attention Deficit
Valerie H. Taylor declares that she has no conflict of interest. Hyperactivity Disorder (ADHD) Rev. 2013. http://www.nimh.nih.
gov/health/topics/attention-deficit-hyperactivity-disorder-adhd/
Human and Animal Rights and Informed Consent This article does index.shtml.
not contain any studies with human or animal subjects performed by any 17. Fliers EA, Buitelaar JK, Maras A, et al. ADHD is a risk factor for
of the authors. overweight and obesity in children. J Dev Behav Pediatr.
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