A final common pathway for depression? Progress toward a general conceptual framework.
Functional neuroimaging studies of depressed patients have converged with functional brain mapping studies of depressed animals in showing that depression is accompanied by a hypoactivity of brain regions involved in positively motivated behavior together with a hyperactivity in regions involved in stress responses. Both sets of changes are reversed by diverse antidepressant treatments. It has been proposed that this neural pattern underlies the symptoms common to most forms of the depression, which are the loss of positively motivated behavior and increased stress. The paper discusses how this framework can organize diverse findings ranging from effects of monoamine neurotransmitters, cytokines, corticosteroids and neurotrophins on depression. The hypothesis leads to new insights concerning the relationship between the prolonged inactivity of the positive motivational network during a depressive episode and the loss of neurotrophic support, the potential antidepressant action of corticosteroid treatment, and to the key question of whether antidepressants act by inhibiting the activity of the stress network or by enhancing the activity of the positive motivational system.
Stone
Eric A
EA
Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. eric.stone@nyu.edu
Lin
Yan
Y
Quartermain
David
D
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001931:Brain Mapping; D016207:Cytokines / Q000627:therapeutic use; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009042:Motivation; D009414:Nerve Growth Factors / Q000627:therapeutic use; D009434:Neural Pathways; D012201:Reward; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology*
D000305:Adrenal Cortex Hormones; D000928:Antidepressive Agents; D016207:Cytokines; D009414:Nerve Growth Factors