Positive Association Between Posterior Subgenual Cingulate and Pituitary Volumes in Psychotic Major Depression

Posterior subgenual cingulate cortex has been consistently linked with the pathophysiology of major depression in both structural and functional brain imaging studies.Likewise, the hyperactivity of the hypothalamic-pituitary-adrenal axis in major depression is well established, especially in its psychotic subtype.Moreover, posterior subgenual cingulate cortex exerts an inhibitory effect on the hypothalamic-pituitary-adrenal axis.While studies show pituitary volume to be a valid marker of hypothalamic-pituitary-adrenal axis activity, none have investigated the volumetric relationships between posterior subgenual cingulate cortex and pituitary volume in subtypes of major depressive disorder, which was precisely the aim of our study.We hypothesized a differential volumetric relationship in psychotic depression.We assessed posterior subgenual cingulate and pituitary volume using Magnetic Resonance Imaging scanning and investigated their volumetric relationships in 39 patients with major depressive disorder (17 psychotic and 22 melancholic) and 18 normal controls.We found strong positive correlations between both left and right posterior subgenual volumes and pituitary volume only in the psychotic depression group (left: r s =0.77, p<0.001, right: r s =0.67, p=0.003).These positive associations were confirmed by regression analyses controlling for patient's age and type of medications.By contrast, no significant volumetric associations were detected in the groups of melancholic patients and normal controls.Our findings provide support to the hypothesis that posterior subgenual cingulate is differentially involved in the pathophysiology of psychotic symptoms in major depressive disorder.