title: Depressive disorder may be associated with raphe nuclei lesions in patients with brainstem infarction.
abstract: Depression is a common symptom after stroke, but its neural substrates remain unclear. The ascending serotonergic system originates from the raphe nuclei in the brainstem. We hypothesized that depressive disorder due to brainstem infarction is associated with damage to the raphe nuclei.
  
  
  
  We prospectively enrolled 19 patients who had the first-ever acute isolated brainstem infarction in an observational cross-sectional study. All patients were evaluated by using the Montgomery Åsberg Depression Rating Scale (MADRS), the clinician-rated version of Apathy Evaluation Scale (AES-C) and Mini-Mental State Examination (MMSE). Depressive disorder was diagnosed according to DSM-5 and MADRS score of 12 or greater. Diffusion tensor imaging and proton density-weighted images were used to identify damage in the raphe nuclei. Accordingly, patients were classified into either the raphe-nuclei-damaged or intact group. Prevalence of depressive disorder and the MADRS, AES-C, and MMSE scores were compared between the two groups.
  
  
  
  Depressive disorder was more frequent in the damaged group (n=6) than in the intact group (n=13) (83% vs. 15%; P=0.01). MADRS scores were higher in the damaged group than in the intact group (mean±1 SD, 17.5±7.9 vs. 7.0±4.4; P=0.002), whereas the AES-C and MMSE scores did not differ between groups.
  
  
  
  We did not assess the damage to the ascending projection fibers from the raphe nuclei.
  
  
  
  Our results suggest that damage to the raphe nuclei underlies depressive disorder due to brainstem infarction, possibly via serotonergic denervation.
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Numasawa
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hattori
authors.affiliation: Department of Rehabilitation Medicine, Sapporo Medical University School of Medicine, Hokkaido, Japan.
authors.forename: Sumio
authors.initials: S
authors.lastname: Ishiai
authors.affiliation: Department of Neurology, JA Toride Medical Center, Ibaraki, Japan.
authors.forename: Zen
authors.initials: Z
authors.lastname: Kobayashi
authors.affiliation: Department of Neurology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kamata
authors.affiliation: Department of Neurology, Tsuchiura Kyodo General Hospital, Ibaraki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Kotera
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Ishibashi
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sanjo
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan; National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.affiliation: Department of Neurology and Neurological Science, Tokyo Medical and Dental University, Tokyo, Japan. Electronic address: yokonuro@tmd.ac.jp.
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000368:Aged; D020526:Brain Stem Infarctions / Q000473:pathology* / Q000523:psychology*; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011446:Prospective Studies; D011903:Raphe Nuclei / Q000473:pathology*
keywords: Apathy; Diffusion tensor imaging; Dorsal raphe nucleus; Median raphe nucleus; Post-stroke depression; Serotonergic system