Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs

Delacrétaz, Aurélie; Santos, Patricia Lagares; Saigí-Morgui, Núria; Vandenberghe, Frederik; Glatard, Anaïs; Gholam‐Rezaee, Mehdi; Gunten, Armin von; Conus, Philippe; Eap, Chin B.

doi:10.1097/fpc.0000000000000313

Cited by 9 publications

(4 citation statements)

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“…These results can be explained by the fact that individuals who suffer from mental disorders are more prone to develop weight gain than individuals from the general population, owing to the prescription of obesogenic psychotropic drugs but also to other factors including limited access to general somatic care and/or unhealthy lifestyle choices (e.g., physical inactivity, poor diet and high rates of cigarette smoking). In this way, greater influences of certain genetic variants on metabolic features have been reported in patients suffering from mental disorders as compared to the general population [18,[50][51][52]. Of note, the important contribution of some genetic markers on metabolic side effects induced by psychotropic drugs may be explained by the hypothesis that psychotropic drugs, that are very recent in the scale of human evolutionary history and applied to only a small fraction of the population, may have not yet been subject to strong natural selection, i.e., the frequency of associated genetic markers have not been strongly influenced.…”

Section: Discussionmentioning

confidence: 99%

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis

Sjaarda

Delacrétaz

Dubath³

et al. 2023

Mol Psychiatry

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Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10−8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

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Section: Discussionmentioning

confidence: 99%

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis

Sjaarda

Delacrétaz

Dubath³

et al. 2023

Mol Psychiatry

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“…Some biomarkers of pro‐inflammatory status (Visfatin) decreased . Several metabolic effects were associated with genetic variants in pharmacodynamic receptor pathways or in energy homeostasis regulating genes …”

Section: Discussionmentioning

confidence: 99%

“…Weight gain is widely known as an adverse effect associated with the use of antidepressants and antipsychotics that occurs in individuals affected by depression, bipolar disorders, schizophrenia, dementia, and ASD . Metabolic conditions often worsen in individuals using antidepressants or antipsychotics . As a consequence of higher incidence of mental disorders, the US Food and Drug Administration (FDA) advises about the side effects of these types of medications.…”

Section: Introductionmentioning

confidence: 99%

Effects of antidepressant and antipsychotic use on weight gain: A systematic review

2019

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Weight gain is an adverse effect of antidepressants and antipsychotics. This side effect can lead to numerous comorbidities and reduces life expectancy. The use of these drugs is increasing worldwide, and the weight gain produced by them represents a common clinical challenge. The goal of this systematic review was to evaluate the potential association of antidepressant and antipsychotic therapy with body weight gain in cohort studies. A search of cohort studies investigating the association between weight gain and the use of antidepressants and antipsychotics in individuals was conducted through the PubMed database from 1 January 2008 to 31 January 2019 following the PRISMA statement. We found 27 independent eligible cohort studies that included children (2-18 years old) and adult (18-103 years old) subjects.Most of the included studies showed a 5% weight gain in individuals using antidepressant therapy. However, Quetiapine, Haloperidol, Trifluoperazine, Risperidone, Aripiprazole, Olanzapine, and Clozapine increased body weight ≥7% from baseline, which is considered a clinically significant result. Weight loss was found in individuals treated with Bupropion. Further cohort studies with higher sample sizes and longer durations of treatment are needed to confirm our observations. KEYWORDS antidepressant, antipsychotic, drug, weight gain, mental disorders 1 | BACKGROUND During the last decade, the prevalence of mental disorders has increased, comprising of 22.8% the global disease burden 1 and causing significant effects on people's health with negative socio-economic consequences. 2 There are 350 million people affected by mental disorders around the world 3 . The disorders include depression, bipolar disorders, schizophrenia and other psychosis, dementia, and developmental disorders (autism spectrum disorder [ASD]). The World Health Organization (WHO) indicates that mental disorders affect people from any age, social condition, or country. 4 Depression is the most common mental disorder. This disease may produce mental distress and also influences simple daily tasks affecting family and work relationships. 2 Moreover, depression is considered as the main cause of disability, contributing to a high morbidity and mortality. 2 In the worst-case scenario, depression can lead to suicide, which nowadays is considered the second leading cause of death among people 15 to 29 years old. 4 When talking about this disease, the WHO gives special attention to the three most affected population groups nowadays, which are young people from 15 to 24, women in childbearing age (especially after child birth), and people over 60 years old. The WHO estimates that the number of people affected

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“…It includes high waist circumference (WC), high triglyceridemia (TG), high blood pressure (BP), high fasting plasma glucose (FPG), and low high-density lipoprotein cholesterolemia (HDL-C). It is established that the use of antidepressants and antipsychotics can lead to weight gain among individuals who suffer from depression, bipolar disorder, or schizophrenia (Delacrétaz et al, 2017 ; Salvi, Mencacci, & Barone-Adesi, 2016b ). In turn, weight gain was also prospectively associated with onset of MetS.…”

Section: Introductionmentioning

confidence: 99%

Non-overweight depressed patients who respond to antidepressant treatment have a higher risk of later metabolic syndrome: findings from the METADAP cohort

et al. 2023

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Background Major depressive disorder (MDD) is a complex disorder with a significant public health burden. Depression remission is often associated with weight gain, a major risk factor for metabolic syndrome (MetS). The primary objective of our study was to assess prospectively the impact of response to antidepressant treatment on developing MetS in a sample of MDD patients with a current major depressive episode (MDE) and who are newly initiating their treatment. Methods In the 6-month prospective METADAP cohort, non-overweight patients, body mass index <25 kg/m2, with MDD and a current MDE were assessed for treatment response after 3 months of treatment, and incidence of MetS after 3 and 6 months of treatment. Outcome variables were MetS, number of MetS criteria, and each MetS criterion (high waist circumference, high blood pressure, high triglyceridemia, low high-density lipoprotein-cholesterolemia, and high fasting plasma glucose). Results In total, 98/169 patients (58%) responded to treatment after 3 months. A total of 2.7% (1/38) developed MetS out of which 12.7% (10/79) (p value < 0.001) had responded to treatment after 3 months. The fixed-effect regression models showed that those who responded to treatment after 3 months of follow-up had an 8.6 times higher odds of developing MetS (odds ratio = 8.58, 95% confidence interval 3.89–18.93, p value < 0.001). Conclusion Compared to non-responders, non-overweight patients who responded to treatment after 3 months of antidepressant treatment had a significantly higher risk of developing MetS during the 6 months of treatment. Psychiatrists and nurses should closely monitor the metabolic profile of their patients, especially those who respond to treatment.

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Influence of polygenic risk scores on lipid levels and dyslipidemia in a psychiatric population receiving weight gain-inducing psychotropic drugs

Cited by 9 publications

References 50 publications

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis

Identification of four novel loci associated with psychotropic drug-induced weight gain in a Swiss psychiatric longitudinal study: A GWAS analysis

Effects of antidepressant and antipsychotic use on weight gain: A systematic review

Non-overweight depressed patients who respond to antidepressant treatment have a higher risk of later metabolic syndrome: findings from the METADAP cohort

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