title: Increased brain serotonin turnover in panic disorder patients in the absence of a panic attack: reduction by a selective serotonin reuptake inhibitor.
abstract: Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.
authors.affiliation: Baker Heart Research Institute, Melbourne, Vic., Australia. murray.esler@baker.edu.au
authors.forename: Murray
authors.initials: M
authors.lastname: Esler
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Lambert
authors.forename: Marlies
authors.initials: M
authors.lastname: Alvarenga
authors.forename: Florentia
authors.initials: F
authors.lastname: Socratous
authors.forename: Jeff
authors.initials: J
authors.lastname: Richards
authors.forename: David
authors.initials: D
authors.lastname: Barton
authors.forename: Ciaran
authors.initials: C
authors.lastname: Pier
authors.forename: Celia
authors.initials: C
authors.lastname: Brenchley
authors.forename: Tye
authors.initials: T
authors.lastname: Dawood
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Hastings
authors.forename: Ling
authors.initials: L
authors.lastname: Guo
authors.forename: Deepak
authors.initials: D
authors.lastname: Haikerwal
authors.forename: David
authors.initials: D
authors.lastname: Kaye
authors.forename: Garry
authors.initials: G
authors.lastname: Jennings
authors.forename: Victor
authors.initials: V
authors.lastname: Kalff
authors.forename: Michael
authors.initials: M
authors.lastname: Kelly
authors.forename: Glen
authors.initials: G
authors.lastname: Wiesner
authors.forename: Gavin
authors.initials: G
authors.lastname: Lambert
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D016022:Case-Control Studies; D002405:Catheterization, Central Venous; D002406:Catheterization, Peripheral; D002560:Cerebrovascular Circulation; D015283:Citalopram / Q000494:pharmacology / Q000627:therapeutic use*; D005838:Genotype; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000097:blood / Q000378:metabolism*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D016584:Panic Disorder / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012107:Research Design; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015283:Citalopram; D006897:Hydroxyindoleacetic Acid; D008734:Methoxyhydroxyphenylglycol; D009638:Norepinephrine; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C010117:3,4-dihydroxyphenylglycol