title: Striatal dopamine transporter availability in drug-naive patients with schizophrenia: a case-control SPECT study with [(99m)Tc]-TRODAT-1 and a meta-analysis.
abstract: Central dopaminergic hyperactivity has been one of the main hypotheses of the pathophysiology of schizophrenia since the 1970s. Excess dopamine (DA) neurotransmission in the striatum is hypothesized to alter the processing of information and result in psychotic symptoms in schizophrenia. Single photon emission computerized tomography (SPECT) provides in vivo indices of DA neurotransmission. Our study aimed to compare dopamine transporter (DAT) availability between drug-naive patients with schizophrenia and controls using SPECT. DAT availability through [(99m)Tc]-TRODAT-1 SPECT was compared between 47 drug-naive patients with recent-onset schizophrenia and 112 healthy controls. We also conducted a random-effects meta-analysis of the available literature synthesizing the results of 6 comparable published articles as well as our current data. The mean specific striatal binding showed a statistical trend for a reduction among the patients compared with controls (estimated difference = 0.071; 95% CI -0.01, 0.15; P = .08). There was an effect of gender, whereby females had a higher ratio of specific striatal binding than males. Age was negatively correlated with the ratio of specific striatal binding, both in patients and controls. The meta-analysis provided a pooled standardized effect size (Cohen's d) of -0.07 (95% CI -0.31, 0.18; P = .60) for the patient vs control comparison in TRODAT binding, with no evidence of heterogeneity between studies or publication bias. Our findings suggest that striatal DAT levels are not altered in the early stages of schizophrenia before medication is introduced. We identified gender differences and aging effects that could have significance for future studies.
authors.affiliation: Department of Psychiatry, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kao Chin
authors.initials: KC
authors.lastname: Chen
authors.forename: Yen Kuang
authors.initials: YK
authors.lastname: Yang
authors.forename: Oliver
authors.initials: O
authors.lastname: Howes
authors.forename: I Hui
authors.initials: IH
authors.lastname: Lee
authors.forename: Sabine
authors.initials: S
authors.lastname: Landau
authors.forename: Tzung Lieh
authors.initials: TL
authors.lastname: Yeh
authors.forename: Nan Tsing
authors.initials: NT
authors.lastname: Chiu
authors.forename: Po See
authors.initials: PS
authors.lastname: Chen
authors.forename: Ru Band
authors.initials: RB
authors.lastname: Lu
authors.forename: Anthony S
authors.initials: AS
authors.lastname: David
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000378:metabolism*; D012737:Sex Factors; D015899:Tomography, Emission-Computed, Single-Photon; D014326:Tropanes; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C493214:SLC6A3 protein, human; D014326:Tropanes; C104196:technetium Tc 99m TRODAT-1