title: Neuropsychological task performance in bipolar spectrum illness: genetics, alcohol abuse, medication and childhood trauma.
abstract: BACKGROUND
  Impaired executive and memory function is a putative genetic trait marker of bipolar I disorder (BPD I). Although executive/memory function has been posited to be an endophenotype of BPD I, it is unclear whether this extends to bipolar spectrum illness. It is also unclear to what extent non-genetic factors such as childhood abuse, alcoholism and medication influence neurocognitive function. We assessed the neuropsychological performance of a large cohort of bipolar disorder probands and their affectively ill and healthy family members, while controlling for self-reported childhood sexual and emotional abuse, emotional neglect, alcohol abuse and medication.
  
  
  METHODS
  A total of 230 largely euthymic participants from 47 families, comprising 49 subjects with BPD I, 19 with bipolar II disorder (BPD II), 44 with recurrent major depression (MDE-R), 33 with a single lifetime episode of depression (MDE-S), 20 with other DSM-IV diagnoses and 65 unaffected relatives, were assessed with a battery of neuropsychological tasks.
  
  
  RESULTS
  Sexual abuse, emotional abuse and emotional neglect scores were associated with poorer cognitive performance. After controlling for childhood trauma, the BPD I group performed worse than unaffected relatives on tests of visual recall memory as well as verbal recall and recognition memory. In contrast, individuals with BPD II and bipolar spectrum illness did not differ significantly from unaffected relatives. Treatment with lithium and antipsychotic medication was associated with reduced executive and verbal recognition memory function. After controlling for medication and other covariates, only verbal recall memory was significantly impaired in the BPD I cohort.
  
  
  CONCLUSIONS
  Verbal recall deficits may be one manifestation of a genetically driven dysfunction of frontal-striatal cortical networks in BPD I.
authors.affiliation: Division of Human Genetics, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. savitzj@mail.nih.gov
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Savitz
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
authors.forename: Mark
authors.initials: M
authors.lastname: Solms
authors.forename: Rajkumar S
authors.initials: RS
authors.lastname: Ramesar
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications*; D000928:Antidepressive Agents / Q000009:adverse effects; D001714:Bipolar Disorder / Q000188:drug therapy / Q000209:etiology / Q000523:psychology*; D002648:Child; D002649:Child Abuse / Q000523:psychology*; D003072:Cognition Disorders / Q000139:chemically induced / Q000150:complications; D015331:Cohort Studies; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012720:Severity of Illness Index
chemical_list: D000928:Antidepressive Agents