Following prescription of weight gain-inducing psychotropic drugs, a 5% threshold for weight gain after 1 month should raise clinician concerns about weight-controlling strategies.

Early modifications of blood lipid levels following prescription of psychotropic drugs inducing dyslipidemia should therefore raise questions on clinical strategies to control long-term dyslipidemia.

Philippe Conus and Chin B. Eap, Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression, Journal of Affective Disorders, http://dx.doi.org/10. 1016/j.jad.2016.03.031 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Study objectives Insomnia disorders as well as cardiometabolic disorders are highly prevalent in the psychiatric population compared to the general population. We aimed to investigate their association and evolution over time in a Swiss psychiatric cohort. Methods Data for 2861 patients (8954 observations) were obtained from two prospective cohorts (PsyMetab and PsyClin) with metabolic parameters monitored routinely during psychotropic treatment. Insomnia disorders were based on the presence of ICD-10 “F51.0" diagnosis (non-organic insomnia), the prescription of sedatives before bedtime or the discharge letter. Metabolic syndrome was defined using the International Diabetes Federation definition, while the 10-year risk of cardiovascular event or death was assessed using the Framingham Risk Score and the Systematic Coronary Risk Estimation, respectively. Results Insomnia disorders were observed in 30% of the cohort, who were older, predominantly female, used more psychotropic drugs carrying risk of high weight gain (olanzapine, clozapine, valproate) and were more prone to suffer from schizoaffective or bipolar disorders. Multivariate analyses showed that patients with high body mass index (OR = 2.02, 95%CI [1.51–2.72] for each ten-kg/m2 increase), central obesity (OR = 2.20, [1.63–2.96]), hypertension (OR = 1.86, [1.23–2.81]), hyperglycemia (OR = 3.70, [2.16–6.33]), high density lipoprotein hypocholesterolemia in women (OR = 1.51, [1.17–1.95]), metabolic syndrome (OR = 1.84, [1.16–2.92]) and higher 10-year risk of death from cardiovascular diseases (OR = 1.34, [1.17–1.53]) were more likely to have insomnia disorders. Time and insomnia disorders were associated with a deterioration of cardiometabolic parameters. Conclusions Insomnia disorders are significantly associated with metabolic worsening and risk of death from cardiovascular diseases in psychiatric patients.

Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.

Background: Psychiatric patients are known to be at high risk of developing cardiovascular diseases (CVDs), leading to an increased mortality rate. Objectives: To assess the CVD risk (presence of metabolic syndrome (MetS) and calculated 10-year CVD risk) in a Swiss psychiatric cohort taking weight gain inducing psychotropic drugs, compare the findings to a Swiss population-based cohort, and evaluate the prevalence of participants treated for metabolic disruptions in both cohorts. Methods: Data for 1,216 psychiatric patients (of whom 634 were aged 35-74 years) were obtained between 2007 and 2017 from a study with metabolic parameters monitored during psychotropic treatment and between 2003 and 2006 for 6733 participants from the population-based CoLaus¦PsyCoLaus study. Results: MetS as defined by the International Diabetes Federation (IDF) was identified in 33% of the psychiatric participants and 24.7% of the population-based subjects. Specifically, prevalence per the IDF definition was more than 3 times higher in the psychiatric cohort among women aged 35 to 49 years (25.6% versus 8.0%; p<10-4). The psychiatric and population-based cohorts, respectively, had comparable predicted CVD risk (10-year risk of CVD event >20%: 0% versus 0.1% in women and 0.3% versus 1.8%, p=.01 in men; 10-year risk of CVD deaths >5%: 8.5% versus 8.4%, p=.58, in women and 13.4% versus 16.6%, p=.42 in men). No difference was observed among the proportion of participants with MetS treated for metabolic disturbances in the two cohorts, with the exception of women aged 35-49 years, for whom those in the psychiatric cohort were half as likely to receive treatment compared to participants in CoLaus¦PsyCoLaus (17.8% versus 38.8% per the IDF definition; p=.0004). Conclusion: These findings emphasize the concern that psychiatric patients present an altered metabolic profile and that they do not receive adequate treatment for metabolic disruptiuons. Presence of metabolic disturbances should be routinely assessed, and adequate follow-up is needed to intervene early after illness onset.

Weight gain and metabolic complications are major adverse effects of many psychotropic drugs. We aimed to understand how socio-economic status (SES), defined as the Swiss socio-economic position (SSEP), is associated with cardiometabolic parameters after initiation of psychotropic medications known to induce weight gain. Cardiometabolic parameters were collected in two Swiss cohorts following the prescription of psychotropic medications. The SSEP integrated neighborhood-based income, education, occupation, and housing condition. The results were then validated in an independent replication sample (UKBiobank), using educational attainment (EA) as a proxy for SES. Adult patients with a low SSEP had a higher risk of developing metabolic syndrome over one year versus patients with a high SSEP (Hazard ratio (95% CI) = 3.1 (1.5–6.5), n = 366). During the first 6 months of follow-up, a significant negative association between SSEP and body mass index (BMI), weight change, and waist circumference change was observed (25 ≤ age < 65, n = 526), which was particularly important in adults receiving medications with the highest risk of weight gain, with a BMI difference of 0.86 kg/m2 between patients with low versus high SSEP (95% CI: 0.03–1.70, n = 99). Eventually, a causal effect of EA on BMI was revealed using Mendelian randomization in the UKBiobank, which was notably strong in high-risk medication users (beta: −0.47 SD EA per 1 SD BMI; 95% CI: −0.46 to −0.27, n = 11,314). An additional aspect of personalized medicine was highlighted, suggesting the patients’ SES represents a significant risk factor. Particular attention should be paid to patients with low SES when initiating high cardiometabolic risk psychotropic medications.

Obesity development during psychotropic treatments represents a major health issue in psychiatry. Melanin-concentrating hormone receptor 2 (MCHR2) is a central receptor involved in energy homeostasis. MCHR2 shares its promoter region with MCHR2-AS1, a long antisense non-coding RNA. The aim of this study was to determine whether tagging single nucleotide polymorphisms (tSNPs) of MCHR2 and MCHR2-AS1 are associated with the body mass index (BMI) in the psychiatric and in the general population. The influence of MCHR2 and MCHR2-AS1 tSNPs on BMI was firstly investigated in a discovery psychiatric sample (n1 = 474). Positive results were tested for replication in two other psychiatric samples (n2 = 164, n3 = 178) and in two population-based samples (CoLaus, n4 = 5409; GIANT, n5 = 113809). In the discovery sample, TT carriers of rs7754794C>T had 1.08 kg/m2 (p = 0.04) lower BMI as compared to C-allele carriers. This observation was replicated in an independent psychiatric sample (-2.18 kg/m2; p = 0.009). The association of rs7754794C>T and BMI seemed stronger in subjects younger than 45 years (median of age). In the population-based sample, a moderate association was observed (-0.17 kg/m2; p = 0.02) among younger individuals (<45y). Interestingly, this association was totally driven by patients meeting lifetime criteria for atypical depression, i.e. major depressive episodes characterized by symptoms such as an increased appetite. Indeed, patients with atypical depression carrying rs7754794-TT had 1.17 kg/m2 (p = 0.04) lower BMI values as compared to C-allele carriers, the effect being stronger in younger individuals (-2.50 kg/m2; p = 0.03; interaction between rs7754794 and age: p-value = 0.08). This study provides new insights on the possible influence of MCHR2 and/or MCHR2-AS1 on obesity in psychiatric patients and on the pathophysiology of atypical depression.