title: Anxiety is associated with reduced central serotonin transporter availability in unmedicated patients with unipolar major depression: a [11C]DASB PET study.
abstract: Serotonergic dysfunction may contribute to negative mood states in affective disorders. Some in vivo imaging studies showed reduced availability of serotonin transporters (5-HTT) in the brainstem and thalamus of patients with major depression. We tested the hypothesis that 5-HTT availability is reduced in unmedicated unipolar patients with major depression compared to healthy control subjects matched for gender, age, genotype and smoking status. Availability of 5-HTT was measured in vivo with positron emission tomography and [(11)C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB) in the midbrain, thalamus and amygdala. DASB binding was correlated with the severity of depression (Beck's Depression Inventory), anxiety (Spielberger's State-Trait Anxiety Inventory) and personality traits (Temperament and Character Inventory). Patients with major depression displayed reduced 5-HTT availability in the thalamus (P=0.005). In patients, low serotonin transporter availability correlated with high anxiety (thalamus: r=-0.78, P=0.004; midbrain: r=-0.78, P=0.004; amygdala: r=-0.80, P=0.003). Correlations with severity of depression were weaker and did not survive correction for multiple testing. These results support the hypothesis that central serotonergic dysfunction is associated with negative mood states in affective disorders. In the thalamus, a low serotonin reuptake capacity may interfere with thalamic control of cortical excitability and contribute to anxiety rather than depression per se in major depression.
authors.affiliation: Department of Nuclear Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Reimold
authors.forename: A
authors.initials: A
authors.lastname: Batra
authors.forename: A
authors.initials: A
authors.lastname: Knobel
authors.forename: M N
authors.initials: MN
authors.lastname: Smolka
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
authors.forename: K
authors.initials: K
authors.lastname: Mann
authors.forename: C
authors.initials: C
authors.lastname: Solbach
authors.forename: G
authors.initials: G
authors.lastname: Reischl
authors.forename: F
authors.initials: F
authors.lastname: Schwärzler
authors.forename: G
authors.initials: G
authors.lastname: Gründer
authors.forename: H-J
authors.initials: HJ
authors.lastname: Machulla
authors.forename: R
authors.initials: R
authors.lastname: Bares
authors.forename: A
authors.initials: A
authors.lastname: Heinz
mesh_terms: D001007:Anxiety / Q000378:metabolism*; D001596:Benzylamines; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D003866:Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007407:Interviews as Topic; D049268:Positron-Emission Tomography; D011859:Radiography; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: D001596:Benzylamines; D002250:Carbon Radioisotopes; C420885:N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine; D050486:Serotonin Plasma Membrane Transport Proteins