Depression, Stress, and Anhedonia: Toward a Synthesis and Integrated Model

Depression is a significant public health problem, but its etiology and pathophysiology remain poorly understood. Such incomplete understanding likely arises from the fact that depression encompasses a heterogeneous set of disorders. To overcome these limitations, renewed interest in intermediate phenotypes (endophenotypes) has resurfaced, and anhedonia has emerged as one of the most promising endophenotypes of depression. Here, a heuristic model is presented postulating that anhedonia arises from dysfunctional interactions between stress and brain reward systems. To this end, we review and integrate three bodies of independent literature investigating the role of (a) anhedonia, (b) dopamine, and (c) stress in…

• NA
  National Alliance for Research on Schizophrenia and Depression
• NI
  National Institute of Mental Health

  Awards: R01 MH095809, R01 MH068376, MH095809, MH068376
• NC
  National Center for Complementary and Alternative Medicine

  Award: R21 AT002974