title: Black bile: are elevated monoamines an etiological factor in some cases of major depression?
abstract: It was hypothesized decades ago that reduced levels of brain monoamines such as serotonin or norepinephrine form, at least in part, a pathophysiological basis for major depression. Consistent with this hypothesis, a conventional strategy used, with varying success, to treat major depression involves administering antidepressant drugs that are thought to boost the synaptic concentration of serotonin and/or norepinephrine. While the reduced monoamine hypothesis is well known but highly controversial and widely considered to be incomplete or simply incorrect, the possibility that elevated monoamines are an etiological factor in some cases of major depression (rather than or in addition to hypomania or mania) has received little attention at all. This paper puts forth the novel hypothesis elevated brain levels of three monoamines - serotonin, norepinephrine, dopamine - are each etiological factors in some cases of major depression. In support of this hypothesis, the paper very briefly reviews relevant data on each of these neurotransmitter systems, including: transporter knockout mice, human genetic association studies, and pharmaceutical studies that enhance or diminish transmitter signaling in either rodents or humans. While all of the published data do not support the hypothesis, there are studies that do for each of the three transmitter systems. The etiological basis of the putative effect of monoamines on depression may be mediated both through genetics and exposure to psychological stress. If the elevated monoamine hypothesis is correct for some persons, pharmaceutical treatment of depression may be significantly improved if the particular elevated monoamine(s) could be identified and then altered on a personalized basis, or perhaps for different putative subtypes of depression. One possibility is that atypical depression involves elevated noradrenergic signaling.
authors.affiliation: Department of Psychology, Room 3200 ILSB, Texas A&M University, College Station, TX 77843-4235, USA. pfitz@mbi.mb.jhu.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Fitzgerald
mesh_terms: D003865:Major Depressive Disorder / Q000209:etiology*; D004298:Dopamine / Q000009:adverse effects*; D006801:Humans; D008954:Models, Biological; D009638:Norepinephrine / Q000009:adverse effects*; D012701:Serotonin / Q000009:adverse effects*; D015398:Signal Transduction / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications
chemical_list: D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine