title: Interplay between childhood trauma and BDNF val66met variants on blood BDNF mRNA levels and on hippocampus subfields volumes in schizophrenia spectrum and bipolar disorders.
abstract: OBJECTIVE
  Here we investigated a two hit gene environment model in relation to functional genomic factors (BDNF mRNA), and volume of hippocampal subfields in schizophrenia spectrum and bipolar disorders, focusing on both an environmental (childhood trauma) and genetic risk factor (BDNF val66met).
  
  
  METHODS
  A total of 323 patients with a broad DSM-IV schizophrenia spectrum disorder or bipolar disorder were consecutively recruited. A history of childhood trauma was obtained using the Childhood Trauma Questionnaire. BDNF DNA and RNA were analyzed using standardized procedures. A subsample of n = 108 underwent MRI scanning, and the FreeSurfer was used to obtain measures of hippocampal subfield. All MRI data were corrected for age and gender, with post-hoc analysis correcting for ICV.
  
  
  RESULTS
  A history of childhood trauma or being a met carrier of the BDNF val66met was associated with significantly reduced BDNF mRNA level. Additive effects were observed between a history of childhood trauma and BDNF val66met, in the direction of met carriers with high levels of childhood trauma having the lowest BDNF mRNA levels. Lastly, met carriers reporting high levels of childhood trauma (specifically sexual or physical abuse) had significantly reduced hippocampal subfield volumes CA2/3 and CA4 dentate gyrus.
  
  
  CONCLUSIONS
  The current findings demonstrate that the reduced BDNF mRNA levels found in psychosis may be associated with both a history of childhood trauma and BDNF val66met variants. Further, our study supports a two hit model including a history of childhood trauma as well as genetic vulnerability (met carriers of the BDNF val66met) behind reduced volume of hippocampal subfields in psychosis. This was specifically found for areas important for neurogenesis, the CA2/3 and the CA4 DG.
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. Electronic address: monica.aas@medisin.uio.no.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Unn K
authors.initials: UK
authors.lastname: Haukvik
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Tesli
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Athanasiu
authors.affiliation: NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bjella
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Hansson
authors.affiliation: Department of Psychological Medicine, Institute of Psychiatry, King's College London, UK; Neuropsychopharmacology Unit, IRCCS Fatebenefratelli Brescia, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Cattaneo
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Agartz
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: NORMENT, Institute of Clinical Medicine, University of Oslo, Norway; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000097:blood / Q000235:genetics / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000235:genetics*; D002649:Child Abuse / Q000523:psychology*; D005260:Female; D059647:Gene-Environment Interaction; D005838:Genotype; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D012333:RNA, Messenger / Q000378:metabolism*; D012189:Retrospective Studies; D012559:Schizophrenia / Q000097:blood / Q000235:genetics / Q000473:pathology; D011795:Surveys and Questionnaires; D014633:Valine / Q000235:genetics; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D008715:Methionine; D014633:Valine
keywords: BDNF RNA; BDNF val66met; Childhood trauma; Hippocampal subfields; Psychosis