1.
Obesity and mental health
DR WALID SARHAN
SENIOR CONSULTANT PSYCHIATRIST
AMMAN-JORDAN

2.
Intoday's society,leannessisoften equated with beauty,
success,fitness,and self-control
Obesity, onthe other hand, is consideredas undesirableas
leanness is desirable, forreasonsthat are often morerelated
to cosmeticconcernsthan to actual orpotential medical
complications.
Complexphysicalandpsychologicalrelatontionship
Overview

3.
Five types of mental illness appear in the top 20 causes of global burden of disease (GBD):
1. Major depression (second)
2. Anxiety disorders (seventh)
3. Schizophrenia (11th)
4. Dysthymia or persistent depressive disorder (16th)
5. Bipolar disorder (17th)
Global Burden of Mental Illness

4.
Common global psychiatric disorders
Disorder Estimated lifetime prevalence Typical symptoms
Anxiety ~16% • Situational (e.g. phobias) or generalised
• Often comorbid with depression
Mood disorders ~12% • Major depressive disorder
• Persistent low mood, lack of enjoyment
• Low energy, fatigue
• Poor concentration
• Appetite and sleep disturbance
• Suicidal thoughts
• Bipolar disorder
• Episodes of depression and mania/hypomania
Externalising disorders* ~2–15% • Overactive, aggressive or dissocial behaviour
• Poor attention/concentration and focus
Substance misuse** ~1–15% • Intoxication, dependence, withdrawal, psychosis
*attention-deficit/hyperactivity disorder (ADHD), oppositional-defiant disorder (ODD), conduct disorder, intermittent explosive disorder;
**alcohol and illicit drug use and dependence
Kessler et al. Epidemiol Psichiatr Soc 2009;18:23–33

5.
Risk of mental illness in obesity
Lifetime risk of
disorder Simon et al.1 Mather et al.2
All obese Men Women All obese Men Women
Any mood disorder
1.27
(1.15–1.41)
1.21
(0.99–1.46)
1.29
(1.11–1.50)
1.29
(1.12–1.49)
1.17
(0.91–1.50)
1.38
(1.16–1.64)
Any anxiety disorder
1.28
(1.05–1.57)
1.17
(0.82–1.67)
1.34
(1.09–1.64)
1.22
(1.10–1.36)
1.25
(1.06–1.46)
1.20
(1.05–1.38)
Any substance misuse
disorder
0.78
(0.65–0.93)
0.75
(0.60–0.93)
0.88
(0.65–1.18)
– – –
Data are lifetime odds ratio (95% CI) compared with normal weight individuals in all obese individuals, obese men and obese women.
Studies cited are large U.S populations studies
1. Simon et al. Arch Gen Psychiatry 2006;63:824–30; 2. Mather et al. J Psychosom Res 2009;66:277–85

6.
6
Dr.
Latefa
Dardas
The
Global
Burden
of
Mental
Health
Problems

7.
Frequency of Moderate to Severe Depression Symptoms among Adolescents in Jordan
Male Female 7

8.
Help Seeking Intentions among Jordanian Adolescents
8

9.
Meta-analysis of 17 epidemiological studies1
Risk of depression in obese and normal weight individuals (1)
1. de Wit et al. Psychiatry Res 2010;178:230–5
In obese women, odds are 32% higher
than in non-obese
• Male gender did not influence risk
1
OR (95% CI)
Pooled OR: 1.18
(95% CI: 1.01-1.37)
10
0.1 1
OR (95% CI)
Pooled OR: 1.32
(95% CI: 1.23-1.40)
0.1 10
Odds of depression in obese individuals are
18% higher than in non-obese, i.e. obese
individuals are 1.18 times more likely to have
depressive symptoms than non-obese

10.
Large epidemiological surveys1,2
◦ Lifetime odds of depression are significantly greater in extreme obesity (BMI ≥40 kg/m2) vs. normal weight
Risk of depression in obese and normal weight individuals (2)
1. Onyike et al. Am J Epidemiol 2003;58:1136–47; 2. Petry et al. Psychosom Med 2008;70:288–97
CI, confidence interval; NHANES, National Health and Nutrition Examination Survey; NESARC, National Epidemiologic Survey on Alcohol and Related Conditions;
OR odds ratio
1
OR (95% CI)
OR: 2.60
(95% CI: 1.38–4.91)
10
0.1 1
OR (95% CI)
OR: 2.00
(95% CI: 1.74–2.31)
10
0.1
NESARC3
NHANES2

11.
Meta-analysis of 15 longitudinal studies (n=58,745)1
Obesity increased odds of developing depression
◦ OR for developing depression if obese: 1.55 (95% CI: 1.22–1.98; p<0.001)
◦ Effect stronger in US (OR: 2.12) than Europe (OR: 1.33)
◦ Since average BMI in US is higher, observed differences could indicate dose–response relationship. Different sociocultural
mechanisms may also be at play
Depression increased odds for developing obesity
◦ OR: 1.58 (95% CI: 1.33–1.87; p<0.001)
Obesity and depression have a bi-directional relationship (1)
1. Luppino et al. Arch Gen Psychiatry 2010;67:220–9
CI, confidence interval; OR odds ratio

12.
Obesity and depression have a bi-directional relationship (2)
Left hand image
Association between
baseline obesity and
development of
depression
Favours A: negative
association between
BMI and depression
Favours B: positive
association between
BMI and depression
Horizontal lines represent individual studies; filled diamond represent overall finding
Right hand image
Association between
baseline depression
and development of
obesity
Favours A: negative
association between
depression and BMI
Favours B: positive
association between
depression and BMI
BMI ≥30
BMI 25–29.99
1
0.01 0.1 10 100
Favours B
Favours A
OR (95% CI)
1
0.01 0.1 10 100
Favours B
Favours A
OR (95% CI)
1. Luppino et al. Arch Gen Psychiatry 2010;67:220–9

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Winter depression
Atypical
Overeating
Over sleeping
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14.
Drug misuse
Pregablin
Gabapentin
Ceptagon
Opiate
Alcohol
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15.
Physiology of weight regulation
Behavioural Neural
Metabolic Genetic
Learning,
memory, reward,
mood, emotion
Insulin, leptin, gut
hormones, circulating
nutrients
Zheng et al. Int J Obes (Lond) 2009;33(Suppl. 2):S8–13
Food availability,
sedentary lifestyle,
Food cues
Energy intake
Energy
expenditure FTO, IRX3

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Physiological1
Obesity may cause HPA axis and neuroendocrine disturbance, leading to depression
Obesity increases insulin resistance and diabetes, potentially causing depression via cerebral changes
Psychological1
Being overweight causes psychological distress (poor self-esteem, social stigma etc.)
Genetic2
Shared genetic risk of both conditions
Pharmacological3–5
◦ Numerous psychotropic drugs are associated with weight gain including amitriptyline, mirtazapine, paroxetine,
olanzapine and clozapine4,5
Obesity and mental health: potential mechanisms
1. Luppino et al. Arch Gen Psychiatry 2010;67:220–9; 2. Afari et al. Depress Anxiety 2010;27:799–806; 3. Smits et al. J Psychiatr Res 2010;44:1010–16;
4. Serretti, Mandelli. J Clin Psychiatry 2010;71:1259–72; 5. Rummel-Kluge et al. Schizophr Res 2010;123:225–33
HPA, hypothalamic–pituitary–adrenal

17.
Cross-sectional Canadian population study1
◦ n=36,984
◦ Mean BMI: 25.7±4.8 kg/m2
Increased odds of obesity mediated by medication
◦ Odds of obesity greater if taking:
◦ Antidepressants (AOR: 1.50; p<0.0001)
◦ Antipsychotics (AOR: 3.03; p<0.0001)
◦ Risk remained when controlling for other psychotropic medications
Antidepressants and antipsychotics accounted for:
◦ 86% of the relationship between mood disorders and obesity
◦ 32% of the relationship between anxiety disorders and obesity
Antidepressants and antipsychotics increase odds of obesity
Odds adjusted for gender, age, education, physical activity level, Charlson Comorbidity Index scores. AOR, adjusted odds ratio
1. Smits et al. J Psychiatr Res 2010;44:1010–16

18.
Clinical trials show that certain antidepressants and antipsychotics cause weight gain1–3
◦ These include amitriptyline, mirtazapine, paroxetine, olanzapine and clozapine2,3
Certain agents may also cause weight loss2
◦ Bupropion and possibly fluoxetine
Weight gain is associated with development of diabetes, hypertension and dyslipidaemia2,4
Psychotropic-related weight gain may be mediated by:
◦ Gender: women have a greater risk of antipsychotic-induced weight gain5
◦ Cognitive distortions related to weight*5
◦ Cytokines, including TNF-α6
◦ Genetic susceptibility7
Psychotropic agents and weight gain
1. Smits et al. J Psychiatr Res 2010;44:1010–16; 2. Serretti, Mandelli. J Clin Psychiatry 2010;71:1259–72; 3. Rummel-Kluge et al. Schizophr Res 2010;123:225–33;
4. Berkowitz, Fabricatore. Psychiatr Clin N Am 2011;34:747–64; 5. Khazaal et al. Clin Pract Epidemiol Ment Health 2006;2:29;
6. Chen da et al. Schizophr Res 2008;106:367–8; 7. Changnon. Curr Drug Targets 2006;7:1681–95
*strict weight regulation, fear of weight gain, self-control as basis of self-esteem, weight and eating behaviour as basis of approval. TNF, tumour necrosis factor

19.
The GLP-1 receptor agonist exenatide is being investigated for treatment of antipsychotic-associated
weight gain in obese adults with mental illness (NCT00845507, NCT01794429)
Recent guidelines from Canada (Canadian Network for Mood and Anxiety Treatments; CANMAT) state
that “for excess weight, the best-studied pharmacologic approaches are metformin and topiramate,
with emerging evidence for liraglutide and modafinil”1
Medications to offset psychotropic-induced weight gain
1. McIntyre et al. Ann Clin Psychiatry 2012;24:69–81
GLP-1, glucagon-like peptide-1
Liraglutide is not approved for weight management

20.
11.1
8.5
13.2
22.5
35.6
34
43.4
28.6
0
5
10
15
20
25
30
35
40
45
50
Sibutramine
alone
Lifestyle
modification
alone
Combined
therapy
Sibutramine plus
brief therapy
Increased by ≥5 points Decreased by ≥5 points
Effect of weight loss on mood
1-year randomised trial of lifestyle and/or
sibutramine therapy1
◦ Mean overall depression scores* decreased across
all groups (p<0.001)
◦ In 13.9% of participants who lost significantly less
weight, symptoms of depression increased
In a meta-analysis of 31 RCTs, all lifestyle and
medication interventions reduced symptoms of
depression2
1. Faulconbridge et al. Obesity (Silver Spring) 2009;17:1009–16; 2. Fabricatore et al. Int J Obes (Lond) 2011;35:1363–76
*Beck Depression Inventory-II. BMI, body mass index; RCT, randomised controlled trial
194 obese participants
Age: 43.7 ± 10.2 years
BMI: 37.6 ± 4.1 kg/m2
Proportion
of
participants
(%)

21.
Liraglutide for psychiatric disorders: clinical evidence
and challenges
These preliminary results suggest that liraglutide could be a potential add-on
therapeutic strategy against mood disorders to control not only the weight and
metabolic dysfunction of patients, but also coexistent cognitive impairment.
It could also open new venues of investigation of the neurobiology of mood
disorders.
Camkurt, Mehmet Akif, Lavagnino, Luca, Zhang, Xiang Y. and Teixeira, Antonio L. "Liraglutide for psychiatric
disorders: clinical evidence and challenges" Hormone Molecular Biology and Clinical Investigation, vol. 36, no.
2, 2018, pp. 20180031. https://doi.org/10.1515/hmbci-2018-0031

22.
Effect of liraglutide 3.0mg treatment on weight
reduction in obese antipsychotic-treated patients
Liraglutide 3.0 mg significantly decreased body weight in obese
patients treated with antipsychotics without altering the status of
psychiatric diseases.
A randomized controlled study is required to corroborate the
results of this study.
Seung Eun Lee et alPsychiatry Research
Volume 299, May 2021, 113830
7/31/2021 22

23.
Psychiatric disorders are prevalent and have a significant impact on wellbeing and productivity
Mood/anxiety disorders are more common in individuals with obesity
There is a bidirectional relationship between depression and obesity; various mechanisms may be
responsible
Obesity may cause neuroendocrine disturbances which could potentially lead to depression
Certain psychotropic medications, particularly antidepressants and antipsychotics, are associated with
weight gain
Further research is needed to elucidate the relationship between mental health and weight gain, and
to identify potential targets for intervention
Conclusions

24.
wsarhan342gmail.com
Thank you