title: Variants of SLC6A4 in depression risk following severe TBI.
abstract: BACKGROUND
  Post-traumatic depression (PTD) may be a result of several factors like secondary injury chemical cascades as well as psycho-social factors following traumatic brain injury (TBI). While the role of serotonin in the pathology and treatment of idiopathic major depression may be somewhat controversial, it is unclear what role serotonin may play in PTD following a TBI.
  
  
  OBJECTIVE
  To assess serotonergic function and genetic risk for PTD development over 1 year following TBI.
  
  
  METHODS
  Examination of variation in the serotonin transporter gene [SLC6A4 (5-HTTLPR, rs25331, and a variable number of tandem repeats variant in Intron 2)] in 109 subjects with moderate-severe injury. Depression was assessed using the Patient Health Questionnaire (PHQ-9) at 6 and/or 12 months post-injury.
  
  
  RESULTS
  At 6 months post-injury, subjects with a history of pre-morbid mood disorders and 5-HTTLPR L-homozygotes were at greater risk for PTD. Contrary to major depression, subjects without pre-morbid mood disorders (n = 80) and S-carriers were 2.803-times less likely to be depressed compared to L-homozygotes. At 12 months post-injury, LG-carriers were also less likely to experience PTD. Temporal analysis also showed 5-HTTLPR associations in PTD development across recovery.
  
  
  CONCLUSIONS
  This study suggests a unique injury- and temporally-specific interaction between TBI and genetic risk for depression.
authors.affiliation: Center for Neuroscience, University of Pittsburgh , Pittsburgh, PA , USA.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Failla
authors.forename: Josh N
authors.initials: JN
authors.lastname: Burkhardt
authors.forename: Megan A
authors.initials: MA
authors.lastname: Miller
authors.forename: Joelle M
authors.initials: JM
authors.lastname: Scanlon
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Amy K
authors.initials: AK
authors.lastname: Wagner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001930:Brain Injuries / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D003863:Depression / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D005838:Genotype; D015600:Glasgow Coma Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins