The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes

pp 195-210

Neurocognitive Endophenotypes for Bipolar Disorder: Evidence from Case-Control, Family and Twin Studies

  • Eugenia KravaritiAffiliated withLecturer, NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry
  • , Fergus KaneAffiliated withstudent at the section of General Psychiatry, Department of Psychiatry, Institute of Psychiatry
  • , Robin M. MurrayAffiliated withProfessor of Psychiatry, Institute of Psychiatry

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Endophenotypes are observable and quanti-fi able traits, which are considered to be more immediate sequelae of a complex disease genotype than the clinical syndrome. Their presumed greater genetic simplicity and biological proximity to the genetic subst rates, has sparked enthusiasm about a potential role of endophenotypes in the genetic ‘dissection’ of psychiatric disorders. Bipolar illness, and several of its reliable cognitive correlates, have substantial herita-bilities, inviting the hypothesis that the two phenotypes tend to co-occur because they share susceptibility genes. We critically discuss the notion that cognitive dysfunction is integral to the bipolar diathesis by drawing evidence from population based studies of children, adolescents and young adults who develop bipolar illness in later life, studies of euthymic bipolar patients, and investigations of non-bipolar fi rst-degree relatives of affected probands. The balance of the evidence suggests that immediate recall of word lists, and learning that occurs over repeated presentations of list items, deserve consideration as putative endopheno-types for bipolar illness, as do delayed verbal recall, and circumscribed aspects of selective attention, response inhibition and resistance to interference. However, the most consistent evidence from family and twin studies to date involves negative rather than positive fi ndings. In addition, studies with genetically informative designs are scarce, while the assumptions underlying the endophenotypic approach need to undergo rigorous empirical investigation.


Bipolar disorder endophenotype cognitive defi cit family study twin study review