title: A morphometric, immunohistochemical, and in situ hybridization study of the dorsal raphe nucleus in major depression, bipolar disorder, schizophrenia, and suicide.
abstract: BACKGROUND
  Several lines of evidence implicate 5-hydroxytryptamine (5-HT, serotonin) in the pathophysiology of mood disorders and suicide. However, it is unclear whether these conditions include morphological involvement of the dorsal raphe nucleus (DRN), the origin of most forebrain 5-HT innervation.
  
  
  METHODS
  We used morphometric, immunohistochemical, and molecular methods to compare the DRN in post-mortem tissue of 50 subjects (13 controls, 14 major depressive disorder [MDD], 13 bipolar disorder, 10 schizophrenia; 17 of the cases died by suicide). NeuN and PH8 antibodies were used to assess all neurons and serotonergic neurons respectively; 5-HT(1A) autoreceptor expression was investigated by regional and cellular in situ hybridization. Measurements were made at three rostrocaudal levels of the DRN.
  
  
  RESULTS
  In MDD, the area of the DRN was decreased. In bipolar disorder, serotonergic neuronal size was decreased. Suicide was associated with an increased DRN area, and with a higher density but decreased size of serotonergic neurons. Total neuronal density and 5-HT(1A) receptor mRNA abundance were unaffected by diagnosis or suicide. No changes were seen in schizophrenia.
  
  
  CONCLUSIONS
  The results show that mood disorders and suicide are associated with differential, limited morphological alterations of the DRN. The contrasting influences of MDD and suicide may explain some of the discrepancies between previous studies, since their design precluded detection of the effect.
authors: Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
authors: Paul R
authors: PR
authors: Matthews
authors: Paul J
authors: PJ
authors: Harrison
mesh_terms: D000328:Adult; D017660:Autoreceptors / Q000096:biosynthesis; D001714:Bipolar Disorder / Q000378:metabolism* / Q000473:pathology; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011903:Raphe Nuclei / Q000378:metabolism* / Q000473:pathology; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology; D059326:Serotonergic Neurons / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D013405:Suicide
chemical_list: D017660:Autoreceptors; D012701:Serotonin