Sex differences in rates of obesity in bipolar disorder: postulated mechanisms

Baskaran, Anusha; Danielle, S.; Powell, Alissa M.; Jalil, Dalya; McIntyre, Roger S.

doi:10.1111/bdi.12141

Cited by 39 publications

(32 citation statements)

References 91 publications

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“…Our findings suggest that the commonly positive association between obesity and psychiatric disorders reported in observational studies345678 may not correspond to a causal risk-increasing effect (especially for bipolar disorder and schizophrenia). Such associations may have been driven by phenomena such as residual confounding, due to common causes imperfectly accounted for at study design and/or analysis; or reverse causation, due to, for example, side effects of anti-psychotic medication.…”

Section: Discussionmentioning

confidence: 61%

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Body mass index and psychiatric disorders: a Mendelian randomization study

Hartwig

Bowden

Mola

et al. 2016

Sci Rep

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Obesity is a highly prevalent risk factor for cardiometabolic diseases. Observational studies suggest that obesity is associated with psychiatric traits, but causal inference from such studies has several limitations. We used two-sample Mendelian randomization methods (inverse variance weighting, weighted median and MR-Egger regression) to evaluate the association of body mass index (BMI) with three psychiatric traits using data from the Genetic Investigation of Anthropometric Traits and Psychiatric Genomics consortia. Causal odds ratio estimates per 1-standard deviation increment in BMI ranged from 0.88 (95% CI: 0.62; 1.25) to 1.23 (95% CI: 0.65; 2.31) for bipolar disorder; 0.93 (0.78; 1.11) to 1.41 (0.87; 2.27) for schizophrenia; and 1.15 (95% CI: 0.92; 1.44) to 1.40 (95% CI: 1.03; 1.90) for major depressive disorder. Analyses removing potentially influential SNPs suggested that the effect estimates for depression might be underestimated. Our findings do not support the notion that higher BMI increases risk of bipolar disorder and schizophrenia. Although the point estimates for depression were consistent in all sensitivity analyses, the overall statistical evidence was weak. However, the fact that SNP-depression associations were estimated in relatively small samples reduced power to detect causal effects. This should be re-addressed when SNP-depression associations from larger studies become available.

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Section: Discussionmentioning

confidence: 61%

“…There is considerable evidence suggesting an association between obesity and psychiatric disorders, including depression34, bipolar disorder56 and schizophrenia78. Reverse causality could be one of the explanations for this association because increase in body weight is a side effects of some anti-psychotic medications69.…”

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confidence: 99%

Body mass index and psychiatric disorders: a Mendelian randomization study

Hartwig

Bowden

Mola

et al. 2016

Sci Rep

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“…These include metabolic syndrome (MS), migraine, type 2 diabetes mellitus, thyroid disorders, chronic kidney disease, cancer, chronic pain, and obstructive airway disease, among many others. [1][2][3][4][5][6][7][8] Particular emphasis has been placed on characterizing the elevated frequency of MS among patients with BD 4,9 and the postulated role of psychotropic medication in its development and maintenance. 6,7,10,11 Even though a genetically-based predisposition to metabolic dysfunction in BD has been consistently suggested, 12 few studies have evaluated metabolic status in relatives of patients with BD.…”

Section: Introductionmentioning

confidence: 99%

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

Baptista¹,

Sandia²,

Fernández

et al. 2015

Rev. Bras. Psiquiatr.

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Objective: Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD), but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I. Methods: The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-c2 genes. The frequency of MS was compared with that recorded in the local general population. Results: Ninety-three relatives of three adults with BD were evaluated (30 aged , 18 years, 63 aged . 18 years). The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c) levels (all p , 0.05), waist circumference (p = 0.057), and leptin and insulin resistance values (in adults only) were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele. Conclusions: The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees.

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“…Exercise has also been reported to be more effective in females in relation to cognitive decline [29] and may be more effective in the endothelial dysfunction in dementia [12], and the vascular form(s) of the condition [3]. There are also sex differences in obesity (females > males) with lithium responsive conditions such as bipolar diseases [59], as well as other mental illnesses [60]. Thus, a number of lines of evidence which may give rise to the speculation that combinations of the interventions discussed should focus the initial research on post-menopausal female populations with mild disease or at risk for the cognitive diseases as they may respond more effectively.…”

Section: Discussionmentioning

confidence: 99%

Would Adding Low Doses of Lithium Salts and/or Prebiotic Fibre Interventions to an Effective Exercise Protocol Further Enhance Retention of Cognitive Integrity? Potential for Preventing Loss of Cognition with Aging Using Combinations of Low Cost Regimens

Hart¹

2018

JBiSE

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It is clear that loss of cognition is becoming epidemic in our aging society. Onset of dementia and diseases such as Alzheimer's are very prevalent and the prognosis is not optimistic that numbers will decrease in the coming decades. Thus, this epidemic is impacting the quality of life of a large number of people, primarily females, as well as the health care systems of many countries. Of relevance is the fact that large clinical trials of candidate drugs to treat these conditions have not been overwhelming successes, indicating that we may need to take new directions or focus on prevention. One conservative approach in this regard has been the use of exercise protocols to both retain cognition and inhibit progression of loss. With the optimization of exercise protocols, it may be time to step back and ask "how can these successes be augmented to further inhibit risk and stabilize loss early in the development of these conditions?" An example of how this could be approached is via supplementation with low doses of minerals such as lithium salts, or supplementation of the diet with prebiotics in patients with obesity and metabolic syndrome. Regarding the former, recent epidemiological studies have indicated that the content of Li in the drinking water is associated with lower incidences of cognitive diseases/conditions. While not definitive, such clues may warrant performing controlled studies using low doses of lithium salts plus exer- cise to further optimize impact on retention of cognition in those at risk, or those with early disease. Similarly, patients with obesity are at higher risk to develop dementia, and prebiotics can correct some of the metabolic derangements associated with the microbiome in such patients to impact risk. Thus, multiple low cost interventions plus exercise could further enhance retention of cognitive integrity in specific populations.

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Sex differences in rates of obesity in bipolar disorder: postulated mechanisms

Cited by 39 publications

References 91 publications

Body mass index and psychiatric disorders: a Mendelian randomization study

Body mass index and psychiatric disorders: a Mendelian randomization study

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

Would Adding Low Doses of Lithium Salts and/or Prebiotic Fibre Interventions to an Effective Exercise Protocol Further Enhance Retention of Cognitive Integrity? Potential for Preventing Loss of Cognition with Aging Using Combinations of Low Cost Regimens

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