The neuroscience of mental illness: Building toward the future

Abstract

Mental illnesses arise from dysfunction in the brain. Although numerous extraneural factors influence these illnesses, ultimately, it is the science of the brain that will lead to novel therapies. Meanwhile, our understanding of this complex organ is incomplete, leading to the oft-repeated trope that neuroscience has yet to make significant contributions to the care of individuals with mental illnesses. This review seeks to counter this narrative, using specific examples of how neuroscientific advances have contributed to progress in mental health care in the past and how current achievements set the stage for further progress in the future.

Figure 1.

Mechanistic expansion of psychopharmacologic options. A. Julius Axelrod’s demonstration that reserpine (R), amphetamine (A), impipramine (I) and chlorpromazine (CP) all inhibited reuptake of norepinephrine in various tissues compared to control treatments (C). Reprinted from Ref. . B. The demonstration that antipsychotic efficacy (x-axis) correlates with the strength of antagonism at the dopamine D2 receptor (IC50, y-axis). Reprinted from Ref. .

Figure 2.

Translating biomarkers into mechanistic insight. A. In humans, beta-frequency coherence between the amygdala (AMY) and hippocampus (HPC) correlates with a mixed anxiety and mood measure. Reprinted from Ref. . B. In mice, variation in beta-frequency coherence between the basolateral amygdala (BLA) and ventral hippocampus (vHPC) correlates with open arm time, a measure of anxiety-related avoidance behavior. C, D. In mice, inhibiting somatostatin interneurons in the BLA reduces BLA-vHPC beta coherence (C) and avoidance behavior (D). Figures 2B–D are reprinted from Ref. .

Figure 3.

Understanding mental illness through neuroscience. Genome-wide association studies (GWAS) on illness phenotypes reveal underlying genetic risk, which are mapped to cell biology through the tools of molecular neuroscience. Circuit technologies link function at the level of specific cells and circuit to behavior. Computational approaches refine illness phenotypes, defining the essential components of behavior and how they map onto circuits. Together, these tools have created a virtuous cycle leading to increased understanding of mental illness, paving the way for modern, neuroscience-inspired treatment approaches.