title: High familial risk for mood disorder is associated with low dorsolateral prefrontal cortex serotonin transporter binding.
abstract: Mood disorders are elicited through a combination of genetic and environmental stress factors, and treatment with selective serotonin reuptake inhibitors ameliorates depressive symptoms. Changes in the serotonin transporter (SERT) binding may therefore occur in depressive patients and in subjects at risk for developing depression. The aim of this study was to explore whether abnormalities in SERT might be present in healthy individuals with familial predisposition to mood disorder. Nine individuals at high familial risk (mean age 32.2+/-4.2 years) and 11 individuals at low risk (mean age 32.4+/-5.0 years) for developing mood disorder were included. The subjects were healthy twins with or without a co-twin history of mood disorder identified by linking information from the Danish Twin Register and the Danish Psychiatric Central Register. Regional in vivo brain serotonin transporter binding was measured with [(11)C]DASB PET. The volumes of interest included the orbitofrontal cortex, the dorsolateral prefrontal cortex, the ventrolateral prefrontal cortex, anterior cingulate, caudate, putamen, thalamus, and midbrain. We found that individuals at high familial risk for mood disorders had a 35% reduction in SERT binding in dorsolateral prefrontal cortex (p=0.014, Bonferroni corrected) and on a trend basis a 15% reduction in anterior cingulate (p=0.018, un-corrected). The depression and symptom scores of the high and the low risk individuals were not significantly different. In conclusion, our data suggest that a low SERT binding in dorsolateral prefrontal cortex represents a trait marker for mood disorders.
authors.affiliation: Neurobiology Research Unit and Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital, Denmark. vibe@nru.dk
authors.forename: Vibe G
authors.initials: VG
authors.lastname: Frokjaer
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.forename: Claus
authors.initials: C
authors.lastname: Svarer
authors.forename: William
authors.initials: W
authors.lastname: Baaré
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Joergensen
authors.forename: Karine
authors.initials: K
authors.lastname: Madsen
authors.forename: Jacob
authors.initials: J
authors.lastname: Madsen
authors.forename: Lars V
authors.initials: LV
authors.lastname: Kessing
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
mesh_terms: D000328:Adult; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D004200:Diseases in Twins; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides