Basal ganglia

Anticipation (artificial intelligence)

Nucleus accumbens

Orbitofrontal cortex

Neuroscience

Prefrontal cortex

Cognition

Anterior cingulate cortex

Globus pallidus

Ventral tegmental area

Ventral striatum

Reward system

Computer science

Dopamine

Ventral pallidum

Dopaminergic

Psychology

Central nervous system

Artificial intelligence

Striatum

Neuroimaging

Anhedonia

Progress in Neuro-Psychopharmacology and Biological Psychiatry

Anhedonia is one of the core symptoms of major depressive disorder (MDD), which is often inadequately treated by traditional antidepressants. The modern framework of anhedonia extends the definition from impaired consummatory pleasure or interest in rewards to a broad spectrum of deficits that impact functions such as reward anticipation, approach motivation, effort expenditure, reward valuation, expectation, and reward-cue association learning. Substantial preclinical and clinical research has explored the neural basis of reward deficits in the context of depression, and has implicated mesocorticolimbic reward circuitry comprising the nucleus accumbens, ventral pallidum, ventral tegmental area, amygdala, hippocampus, anterior cingulate, insula, orbitofrontal cortex, and other prefrontal cortex regions. Dopamine modulates several reward facets including anticipation, motivation, effort, and learning. As well, serotonin, norepinephrine, opioids, glutamate, Gamma aminobutyric acid (GABA), and acetylcholine are also involved in anhedonia, and medications targeting these systems may also potentially normalize reward processing in depression. Unfortunately, whereas reward anticipation and reward outcome are extensively explored by both preclinical and clinical studies, translational gaps remain in reward motivation, effort, valuation, and learning, where clinical neuroimaging studies are in the early stages. This review aims to synthesize the neurobiological mechanisms underlying anhedonia in MDD uncovered by preclinical and clinical research. The translational difficulties in studying the neural basis of reward are also discussed.

Anhedonia as a central factor in depression: Neural mechanisms revealed from preclinical to clinical evidence