Circuits regulating pleasure and happiness in major depression

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Selective serotonin reuptake inhibitors (SSRIs) have broadened depression diagnosis.
• Anhedonia, once central to endogenous depression, is now viewed alongside stress-induced morbidity.
• This has increased heterogeneity in major depressive disorder (MDD).

Purpose of the Study:

• To propose a model for understanding MDD heterogeneity.
• To differentiate neuronal circuits regulating anhedonia and dysphoria.
• To explain the roles of limbic and extrapyramidal circuits in mood regulation.

Main Methods:

• Conceptual analysis of existing neurobiological and clinical data.
• Postulation of two interacting cortico-striato-thalamo-cortical (CSTC) circuits.
• Functional differentiation of limbic and extrapyramidal CSTC pathways.

Main Results:

• MDD complexity can be explained by two distinct, interacting neuronal circuits.
• The limbic circuit regulates misery-fleeing behavior (dysphoria).
• The extrapyramidal circuit regulates reward-seeking behavior (anhedonia).

Conclusions:

• Anhedonia and dysphoria arise from distinct but interacting CSTC circuits.
• Hyperactivity in the extrapyramidal circuit leads to craving.
• Hyperactivity in the limbic circuit leads to dysphoria.