Imaging the pathophysiology of major depressive disorder - from localist models to circuit-based analysis

Abstract

The neuroimaging literature of Major Depressive Disorder (MDD) has grown substantially over the last several decades, facilitating great advances in the identification of specific brain regions, neurotransmitter systems and networks associated with depressive illness. Despite this progress, fundamental questions remain about the pathophysiology and etiology of MDD. More importantly, this body of work has yet to directly influence clinical practice. It has long been a goal for the fields of clinical psychology and psychiatry to have a means of making objective diagnoses of mental disorders. Frustratingly little movement has been achieved on this front, however, and the 'gold-standard' of diagnostic validity and reliability remains expert consensus. In light of this challenge, the focus of the current review is to provide a critical summary of key findings from different neuroimaging approaches in MDD research, including structural, functional and neurochemical imaging studies. Following this summary, we discuss some of the current conceptual obstacles to better understanding the pathophysiology of depression, and conclude with recommendations for future neuroimaging research.

Figure 1

Regions, transmitters and circuits implicated in the pathology of major depressive disorder (MDD) by human neuroimaging studies. Past studies have identified alterations in monoamine levels and receptor availability as well as alterations in glutamate and GABA. These neurotransmitter systems participate in larger circuits involved in the experience and regulation of emotion, responses to stress, and processing of rewards. Note: placement of structure labels is approximate. Amyg = amygdala; Caud = Caudate; GABA = GABAergic projections; Glu = glutamatergic projections; Hipp = hippocampus; NAcc = nucleus accumbens; Put = Putamen; SN = substantia nigra; VP = ventral pallidum; VTA = ventral tegmental area. Republished with permission from Treadway and Zald [49].

Figure 2

Schematic depiction of commonly identified functional networks and their associated cognitive and symptom domains. Republished with permission from Buckholtz and Meyer-Lindenberg [150].