title: Decreased histamine H1 receptor binding in the brain of depressed patients.
abstract: The central histaminergic neuron system modulates the wakefulness, sleep-awake cycle, appetite control, learning and memory, and emotion. Previous studies have reported changes in neuronal histamine release and its metabolism under stress conditions in the mammalian brain. In this study, we examined, using positron emission tomography (PET) and [(11)C]-doxepin, whether the histaminergic neuron system is involved in human depression. Cerebral histamine H1 receptor (H(1)R) binding was measured in 10 patients with major depression and in 10 normal age-matched subjects using PET and [(11)C]-doxepin. Data were calculated by a graphical analysis on voxel-by-voxel and ROI (region of interests) basis. Binding potential (BP) values for [(11)C]-doxepin binding in the frontal and prefrontal cortices, and cingulate gyrus were significantly lower in the depressed patients than those in the normal control subjects. There was no area of the brain where [(11)C]-doxepin binding was significantly higher in the depressed patients than in the controls. ROI-based analysis also revealed that BP values for [(11)C]-doxepin binding in the frontal cortex and cingulate gyrus decreased in proportion to self-rating depressive scales scores. The results of this study demonstrate that depressed patients have decreased brain H(1)R binding and that this decrease correlates with the severity of depression symptoms. It is therefore suggested that the histaminergic neuron system plays an important role in the pathophysiology of depression and that its modulation may prove to be useful in the treatment of depression.
authors.affiliation: Department of Behavioural Medicine, Tohoku University School of Medicine, Sendai 980-8575, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
authors.forename: Atshushi
authors.initials: A
authors.lastname: Tashiro
authors.forename: Atshushi
authors.initials: A
authors.lastname: Utsumi
authors.forename: Daisaku
authors.initials: D
authors.lastname: Tamura
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Itoh
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.forename: Motohisa
authors.initials: M
authors.lastname: Kato
authors.forename: Michio
authors.initials: M
authors.lastname: Hongo
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000378:metabolism; D016022:Case-Control Studies; D003863:Depression / Q000000981:diagnostic imaging / Q000378:metabolism*; D004316:Doxepin / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D012044:Regression Analysis; D014055:Tomography, Emission-Computed / Q000379:methods
chemical_list: D002250:Carbon Radioisotopes; D011969:Receptors, Histamine H1; D004316:Doxepin