Association of CRTC1 polymorphisms with obesity markers in subjects from the general population with lifetime depression

- Psychiatric disorders may share common etiological pathways with obesity.
- CRTC1 polymorphisms were not associated with major depression disorder (MDD) in three case-control samples with MDD.
- In PsyCoLaus, CRTC1 rs6510997C>T was significantly associated with lower fat mass in females but not in males.
- In PsyCoLaus, CRTC1 rs6510997C>T was significantly associated with lower fat mass in subjects with MDD but not in controls.
- CRTC1 polymorphisms seem to play a role with obesity markers only in individuals with MDD but not in non-depressive subjects.

BackgroundPsychiatric disorders have been hypothesized to share common etiological pathways with obesity, suggesting related neurobiological bases. We aimed to examine whether CRTC1 polymorphisms were associated with major depressive disorder (MDD) and to test the association of these polymorphisms with obesity markers in several large case-control samples with MDD.MethodsThe association between CRTC1 polymorphisms and MDD was investigated in three case-control samples with MDD (PsyCoLaus n1=3,362, Radiant n2=3,148 and NESDA/NTR n3=4,663). The effect of CRTC1 polymorphisms on obesity markers was then explored.ResultsCRTC1 polymorphisms were not associated with MDD in the three samples. CRTC1 rs6510997C>T was significantly associated with fat mass in the PsyCoLaus study. In fact, a protective effect of this polymorphism was found in MDD cases (n=1,434, β=−1.32%, 95% CI −2.07 to −0.57, p<0.001), but not in controls. In the Radiant study, CRTC1 polymorphisms were associated with BMI, exclusively in individuals with MDD (n=2,138, β=−0.75 kg/m2, 95% CI −1.30 to −0.21, p=0.007), while no association with BMI was found in the NESDA/NTR study.LimitationsEstimated fat mass using bioimpedance that capture more accurately adiposity was only present in the PsyCoLaus sample.ConclusionsCRTC1 polymorphisms seem to play a role with obesity markers in individuals with MDD rather than non-depressive individuals. Therefore, the weak association previously reported in the population-based samples was driven by cases diagnosed with lifetime MDD. However, CRTC1 seems not to be implicated directly in the development of psychiatric diseases.