Psychotropic medications lead to early weight gain in people with psychiatric disorders by altering expression of the CRTC1 gene, a study found.
The study, “Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients,” was published in the journal Clinical Epigenetics.
A complex interplay between genetic and environmental factors underlie metabolic diseases such as obesity.
Patients with bipolar disorder, schizophrenia and major depressive disorder (depression) are at risk of developing metabolic diseases. In part, this is due to the appetite-stimulating side effects of psychotropic medications such as antipsychotics, mood stabilizers, and some antidepressants.
Previous studies suggested that the CRTC1 gene may underlie psychotropic-induced weight gain. Mice lacking this gene became obese and developed other metabolic complications due to an enhanced appetite while eating a normal diet, suggesting that CRTC1 is important in the control of food intake.
This gene also was associated with body fat percentage following an analysis of the genomes of more than 100,000 people from the general population. Epigenetic processes, which refer to changes in gene expression though not to the gene itself, were suggested to explain this association.
One of the possible epigenetic mechanisms is known as DNA methylation, which consists of the addition of a methyl group to a cytosine nucleotide (one of the four building blocks of DNA).
To find out if psychotropic treatments alter the expression of the CRTC1 gene via DNA methylation, a team from Switzerland measured methylation levels in DNA extracted from the blood of 78 patients with psychiatric disorders (median age 37 years). These assessments were done both before beginning treatment with weight gain inducing psychotropic medications and again after one month of treatment.
Psychotic disorders were the most frequent (35 patients), followed by bipolar (18) and schizoaffective (9) disorders.
Half of the patients received psychotropic therapies with a moderate influence on weight gain, including lithium, mirtazapine (brand name Remeron), quetiapine and risperidone (Risperdal). In turn, one-third of the participants were given medications with a high risk for inducing weight gain, including clozapine, olanzapine (Zyprexa), and valproate.
Results showed that, during the first month of treatment, methylation levels were modified significantly at three locations in the CRTC1 gene in patients with early weight gain (of at least 5%) compared to those whose weight remained stable.
After adjusting for factors such as age, sex, psychotropic medication type, length of treatment and early weight gain, the analysis revealed a decrease in DNA methylation at a single site — identified as cg12034943 — that was significantly associated with early weight gain.
A more detailed analysis revealed that cg12034943 was linked significantly to early weight increase in people carrying a mutation in this methylation site of the CRTC1 gene.
“In conclusion, the present study identified a methylation change during the first month of psychotropic treatment in the CRTC1 gene, which was associated with early weight gain during the same period,” the scientists wrote.
“These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects,” they stated in the study.