Left Brain, Right Brain: Atypical Structural Asymmetry in Affective Disorders

Abstract

Despite decades of research, the pathophysiology of psychiatric disorders such as major depressive disorder (MDD) and bipolar disorder (BD) is not well characterized. Accumulating evidence from structural and functional neuroimaging research has revealed aberrant hemispheric left-right asymmetries associated with symptoms of affect that may point to distinct biomarkers characteristic of abnormal emotion-related processes. Yet not only are analyses of hemispheric asymmetry rare in studies of emotion, but the nature of lateralized abnormalities that arise in empirical findings are not often pursued. Thus, the present project identified 39 empirical studies (total n = 23,864 participants) meeting criteria for systematic review and meta-analysis, in order to map the biological substrates of individuals with BD, MDD, and subclinical affective symptoms. Volumetric reductions and cortical thinning were prevalent, with patients with BD characterized by left-lateralized thickness reductions in the frontal cortex. Gray matter loss in individuals with MDD was more widespread and predominated by left-hemisphere and bilateral deficits. Further, healthy controls demonstrated bilateral frontal thinning and reduced asymmetry of the insula and amygdala in association with more severedepressed mood and affective instability. Findings of structural brain asymmetry also varied with heterogeneous age and gender composition of study samples, medication status, childhood trauma, and recurrence history both within and across diagnostic categories. It was implicated that identifying the laterality of anatomical biomarkers of distinct depressive phenotypes may better inform current understanding of psychiatric disease trajectories. Probing how the brain deviates from symmetry along the spectrum of affective functioning may shed light on shared and distinct biosignatures of BD and MDD, as well as guide the development of systematic treatment approaches based on both psychological and biological evidence.