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This issue has been addressed in a number of molecular imaging studies by positron emission tomography or single-photon emission computed tomography of serotonin reuptake sites (5-HTT) in the brain of patients with MDD, with strikingly disparate conclusions. Our meta-analysis of the 18 such studies, totaling 364 MDD patients free from significant comorbidities or medication and 372 control subjects, revealed reductions in midbrain 5-HTT (Hedges' g = \u22120.49; 95% CI: (\u22120.84, \u22120.14)) and amygdala (Hedges' g = \u22120.50; 95% CI: (\u22120.78, \u22120.22)), which no individual study possessed sufficient power to detect. Only small effect sizes were found in other regions with high binding (thalamus: g = \u22120.24, striatum: g = \u22120.32, and brainstem g = \u22120.22), and no difference in the frontal or cingulate cortex. Age emerged as an important moderator of 5-HTT availability in MDD, with more severe reductions in striatal 5-HTT evident with greater age of the study populations ( P&lt;0.01). There was a strong relationship between severity of depression and 5-HTT reductions in the amygdala ( P = 0.01). Thus, molecular imaging findings indeed reveal widespread reductions of \u02dc10% in 5-HTT availability in MDD, which may predict altered spatial-temporal dynamics of serotonergic neurotransmission.<\/jats:p>","DOI":"10.1038\/jcbfm.2014.82","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T04:27:50Z","timestamp":1399436870000},"page":"1096-1103","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":157,"title":["Meta-Analysis of Molecular Imaging of Serotonin Transporters in Major Depression"],"prefix":"10.1177","volume":"34","author":[{"given":"Gregor","family":"Gryglewski","sequence":"first","affiliation":[{"name":"Functional, Molecular & Translational Neuroimaging Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rupert","family":"Lanzenberger","sequence":"additional","affiliation":[{"name":"Functional, Molecular & Translational Neuroimaging Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg S","family":"Kranz","sequence":"additional","affiliation":[{"name":"Functional, Molecular & Translational Neuroimaging Lab, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Friederich-Alexanders Universitaet, Erlangen\/Nurenberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2014,5,7]]},"reference":[{"key":"bibr1-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(79)90053-2"},{"key":"bibr2-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1981.01780310031002"},{"key":"bibr3-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1989.01810070035005"},{"key":"bibr4-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890090104"},{"key":"bibr5-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1177\/026988119200600406"},{"key":"bibr6-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(01)00310-4"},{"key":"bibr7-jcbfm.2014.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2013.10.002"},{"key":"bibr8-jcbfm.2014.82","doi-asserted-by":"crossref","unstructured":"Hahn A, Haeusler D, Kraus C, H\u00f6flich A, Kranz G, Baldinger P, Attenuated serotonin transporter association between dorsal raphe and ventral striatum in major depression. 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