HealthDay News — Variants of a gene are associated with overweight and obesity in psychiatric patients taking drugs that induce weight gain, study findings indicate.

One particular allele of the CREB-regulated transcription coactivator (CRTC1) gene was protective against weight gain in psychiatric patients (P=0.003), Eva Choong, PharmD, PhD, from Lausanne University Hospital in Prilly, Switzerland and colleagues reported in JAMA Psychiatry.

“Our results suggests that CRTC1 plays an important role in the high prevalence of overweight and obesity observed in psychiatric patients,” they wrote, adding it may also help researchers better understand mechanisms of obesity in the general population.

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Obesity is prevalent among patients with psychiatric disorders, especially among those taking medications that induce weight gain, such as atypical antipsychotics and mood stabilizers like lithium and valproate.

Previous research has shown an association between CRTC1 and obesity in animal models, but the gene’s role in human obesity is not understood. So Choong and colleagues whether three CRTC1 polymorphisms were associated with body mass index (BMI) or fat mass in psychiatric outpatients taking weight gain-inducing psychotropic drugs and in the general population.

They looked at retrospective, prospective and population-based data from Lausanne and Geneva university hospitals and a private clinic in Lausanne. The study consisted of an initial sample of 152 psychiatric patients.

The researchers then attempted to replicate their findings in two independent psychiatric samples, consisting of 174 and 118 patients, respectively, and in two population-based samples, consisting of 5,338 people and 123,865 people, respectively.

The researchers found that the polymorphism rs3746266A>G in the CTC1 gene was significantly associated with BMI (P=0.003). In all three psychiatric samples, carriers of this allele had a lower BMI than noncarriers (P=0.001, P=0.05 and P=0.0003, respectively, in each sample).

Among 226 patients not taking other weight gain-inducing drugs, G allele carriers had a significant 1.81-kg/m² lower BMI than non-carriers (P<0.0001).

Women younger than 45 years of age showed the strongest association, with G allele carriers having a 3.87-kg/m² lower BMI than non-carriers (P<0.0001), which accounted for 9% of BMI variance.

Among 123,865 members of the general population, a similar polymorphism rs6510997C>T was significantly associated with lower BMI (P=0.01). In an independent analysis of 5,338 members of the general population, the T allele was significantly associated with lower fat mass (P=0.03), particularly among premenopausal women (P=0.02).

Identifying psychiatric patients at higher risk for weight gain could help clinicians tailor pharmacological treatment in psychiatry, the researchers suggested.

CRTC1 could play a role in the genetics of obesity in the general population, thereby increasing our understanding of the multiple mechanisms influencing obesity,” they added.


  1. Choong E, et al. JAMA Psychiatry. 2013; DOI: 10.1001/jamapsychiatry.2013.187.