Subgenual cingulate volumes in affected and unaffected offspring of bipolar parents

Background: Bipolar disorders (BD) have a strong genetic underpinning, yet no biological vulnerability markers for BD have been identified. Decreased volumes of subgenual cingulate (SGC) were replicated in familial bipolar patients. Presence of abnormality in unaffected subjects at genetic risk for an illness needs to be established before SGC volumes can be used as an endophenotype. This is the first study of SGC volumes in affected and unaffected subjects at familial risk for mood disorders. Method: High-risk participants were recruited from families multiply affected with BD. The high-risk sample included 13 affected and 13 unaffected offspring of bipolar I parents, who were matched by age and sex with 31 controls without a personal or family history of psychiatric disorders. The expanded sample consisted of 24 unaffected, 19 affected subjects all with a first or second degree relative suffering from BD I or II. The age range for all subjects was 15-30 years. Subgenual cingulate volumes were measured on 1.5 T 3D anatomical MRI images using standard methods. Results: We found comparable SGC volumes among unaffected, affected offspring of BD I parents and controls. Likewise no SGC abnormalities were found in the expanded sample of subjects with BD I or II relatives. Left SGC volumes in all groups were smaller than right SGC volumes without laterality by group interaction. The exclusion of 5 medicated subjects did not change the results. Limitations: Cross sectional design, inclusion of both bipolar I and bipolar II probands. Conclusions: Subgenual cingulate volume abnormalities were absent in unaffected or affected relatives of bipolar patients and thus did not meet criteria for endophenotype.