title: Serotonin versus catecholamine deficiency: behavioral and neural effects of experimental depletion in remitted depression.
abstract: Despite immense efforts into development of new antidepressant drugs, the increases of serotoninergic and catecholaminergic neurotransmission have remained the two major pharmacodynamic principles of current drug treatments for depression. Consequently, psychopathological or biological markers that predict response to drugs that selectively increase serotonin and/or catecholamine neurotransmission hold the potential to optimize the prescriber's selection among currently available treatment options. The aim of this study was to elucidate the differential symptomatology and neurophysiology in response to reductions in serotonergic versus catecholaminergic neurotransmission in subjects at high risk of depression recurrence. Using identical neuroimaging procedures with [(18)F] fluorodeoxyglucose positron emission tomography after tryptophan depletion (TD) and catecholamine depletion (CD), subjects with remitted depression were compared with healthy controls in a double-blind, randomized, crossover design. Although TD induced significantly more depressed mood, sadness and hopelessness than CD, CD induced more inactivity, concentration difficulties, lassitude and somatic anxiety than TD. CD specifically increased glucose metabolism in the bilateral ventral striatum and decreased glucose metabolism in the bilateral orbitofrontal cortex, whereas TD specifically increased metabolism in the right prefrontal cortex and the posterior cingulate cortex. Although we found direct associations between changes in brain metabolism and induced depressive symptoms following CD, the relationship between neural activity and symptoms was less clear after TD. In conclusion, this study showed that serotonin and catecholamines have common and differential roles in the pathophysiology of depression.
authors.affiliation: Division of Molecular Psychiatry, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
authors.forename: P
authors.initials: P
authors.lastname: Homan
authors.affiliation: Molecular Imaging Program, Department of Psychiatry and Radiology, New York University School of Medicine, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Neumeister
authors.affiliation: Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, and Department of Health and Human Services, Bethesda, MD, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Nugent
authors.affiliation: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: D S
authors.initials: DS
authors.lastname: Charney
authors.affiliation: 1] Laureate Institute for Brain Research, Tulsa, OK, USA [2] Janssen Pharmaceuticals Research & Development, Titusville, NJ, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Drevets
authors.affiliation: Division of Molecular Psychiatry, Translational Research Center, University Hospital of Psychiatry, University of Bern, Bern, Switzerland.
authors.forename: G
authors.initials: G
authors.lastname: Hasler
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002395:Catecholamines / Q000172:deficiency*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000378:metabolism* / Q000523:psychology*; D004311:Double-Blind Method; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012701:Serotonin / Q000172:deficiency*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D002395:Catecholamines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D012701:Serotonin; D005947:Glucose