Decreased volumes of subgenual cingulate (SGC) have been reported primarily among familial bipolar patients, which is one of the hallmarks of an endophenotype. In order to investigate specificity of SGC volume abnormalities to familial mood disorders and to test whether SGC volumes represent an endophenotype for BD, we measured SGC volumes in young affected and unaffected relatives of bipolar patients (high-risk design) and in sporadic bipolar patients. We included 20 unaffected, 15 affected offspring of bipolar I or bipolar II parents, 18 controls, and 19 sporadic bipolar patients between 15 and 30 years of age. SGC volumes were measured on 1.5 T 3D anatomical MRI images using standard methods. We also combined the effect sizes from all published studies of sporadic patients with mood disorders (N = 61) and controls (N = 84) using random-effect models. We found comparable SGC volumes among unaffected, affected offspring of BD parents and controls (F = 0.7, df = 2; 50, P = 0.47). Likewise no SGC abnormalities were found between sporadic bipolar and control subjects (F = 2.31, df = 1; 34, P = 0.14). When combining all available data from sporadic patients, there were no differences in left (SDM 0.19, 95% CI -0.13 to 0.51) or right (SDM -0.11, 95% CI -0.47 to 0.26) SGC volumes between sporadic bipolar patients and controls. The limitations of the study are cross-sectional design and inclusion of both bipolar I and bipolar II probands. In conclusion, SGC volume abnormalities were absent in unaffected, affected relatives of bipolar patients as well as sporadic bipolar patients and thus did not meet criteria for endophenotype.

Department of Psychiatry Dalhousie University Halifax NS Canada