Orbitofrontal and Cingulate Thickness Asymmetry Associated with Depressive Symptom Dimensions

Both clinical depression and subthreshold depressive symptoms have been associated with alterations in cortical thickness. Studies have yielded conflicting results regarding whether cortical thinning or cortical thickening best characterize the depressive state. Also unclear is whether cortical thickness differences are lateralized. This study examined the relationship between depressive symptom dimensions and cortical thickness asymmetry in cingulate and orbitofrontal regions. Fifty-four community-dwelling adults between the ages of 18 and 81 years received a 3-Tesla magnetic resonance imaging scan and completed the Center for Epidemiologic Studies Depression Scale (CES-D). Cortical thickness values were extracted for the rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, isthmus cingulate, and orbitofrontal cortex. An asymmetry index was calculated for each region. Data were analyzed using separate general linear models for each region, in which the CES-D somatic symptoms, negative affect, and anhedonia subscale scores predicted the asymmetry indices, controlling for age and sex. Higher scores on the anhedonia subscale were associated with right-sided asymmetry in orbitofrontal thickness, whereas higher somatic symptom subscale scores predicted greater left-sided asymmetry in posterior cingulate thickness. Follow-up analyses showed the orbitofrontal effect was specific to the medial, not the lateral, orbitofrontal cortex. These results suggest asymmetries in cortical thickness are apparent at even subthreshold levels of depressive symptoms, as all but five participants were below the CES-D cutoff for clinical depression, and that the relationship varies for different symptom dimensions of depression. Understanding brain asymmetries across the range of depressive symptom severity is important for informing targeted depression treatment.