Major depressive disorder: new clinical, neurobiological, and treatment perspectives

Abstract

In this Seminar we discuss developments from the past 5 years in the diagnosis, neurobiology, and treatment of major depressive disorder. For diagnosis, psychiatric and medical comorbidity have been emphasised as important factors in improving the appropriate assessment and management of depression. Advances in neurobiology have also increased, and we aim to indicate genetic, molecular, and neuroimaging studies that are relevant for assessment and treatment selection of this disorder. Further studies of depression-specific psychotherapies, the continued application of antidepressants, the development of new treatment compounds, and the status of new somatic treatments are also discussed. We address two treatment-related issues: suicide risk with selective serotonin reuptake inhibitors, and the safety of antidepressants in pregnancy. Although clear advances have been made, no fully satisfactory treatments for major depression are available.

Figure 1. Neural systems of relevance to major depressive disorder

Key neural regions implicated in emotion and reward processing, and voluntary and automatic regulation of emotion are shown superimposed on a greyscale depiction of the human brain. DLPFC=dorsolateral prefrontal cortex. mPFC=medial prefrontal cortex. ACC=anterior cingulate cortex. OFC=orbitofrontal cortex. VLPFC=ventrolateral prefrontal cortex. Adapted with permission from reference .

Figure 2. Advances in neurobiology of MDD

MDD=major depressive disorder.

Figure 3. Distinguishing bipolar and unipolar depression with measures of white-matter connectivity

Fractional anisotropy (FA) maps showing three orthogonal ([A] coronal, [B] sagittal, and [C] axial) views of the main effect of group on FA in the region of the left superior longitudinal fasciculus for adults with bipolar depression, unipolar depression, and for healthy controls. MNI152 brain and white-matter skeleton (green) used for randomised analysis. The images represent findings (in red-yellow) projected onto the white-matter skeleton (green). The red-yellow spectrum represents a significance range—ie, 2