Left and Right Hemispheric Lateralization as an Overlooked Variable in Psychiatric Disease: Evidence Across Species

Despite centuries of reports documenting both anatomical and functional brain asymmetries, lateralization as an experimental variable remains largely overlooked in preclinical studies focusing on psychiatric disorders. Recent work has identified standard functional and neuroanatomical asymmetries as well as shifts in typical lateralization in the context of diseased states in model organisms. We have collected and examined studies that investigate the contributions of brain areas in the left and/or right hemisphere to the modulation of emotion and affective processing and discuss the contributions of these areas to functional lateralization of psychiatric processing. We focus our review first on describing documentation of anatomical and functional asymmetries that exist in the healthy brain as well as relevant hypotheses for the evolution of lateralization. Then, we dissect the literature to extract evidence for left/right differences and review these studies to highlight evidence for hemispheric lateralization in several psychiatric areas. The specific focus is on the preclinical literature to emphasize the utility of accessible model organisms to study a fundamental feature of normal and abnormal affective neural processing. As momentum continues to shift toward a renewed appreciation of lateralization across species, the study of anatomical and functional asymmetries at the preclinical level will yield novel insights into psychiatric disease in the coming years. Overall, in this review we summarize the existing literature, emphasize remaining questions, and discuss possible mechanisms for shifts in lateralization associated with psychiatric disorders.