The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder

Neurosci Biobehav Rev. 2017 Feb;73:1-22. doi: 10.1016/j.neubiorev.2016.12.011. Epub 2016 Dec 12.


The phenomenology and underlying pathophysiology of bipolar disorder (BD) are heterogeneous. The identification of putative endophenotypes for BD can aid in the investigation of unique patho-etiological pathways, which may lead to the development of personalised preventative and therapeutic approaches for this multi-faceted disorder. We included original studies involving unaffected first-degree relatives of BD patients (URs) and a healthy control (HC) comparison group with no first-degree family history of mental disorders, investigating: 'cold' and 'hot' cognition and functional and structural neuroimaging. Seventy-seven cross-sectional studies met the inclusion criteria. The present review revealed that URs in comparison with HCs showed: (i) widespread deficits in verbal memory, sustained attention, and executive function; (ii) abnormalities in the reactivity to and regulation of emotional information along with aberrant reward processing, and heightened attentional interference by emotional stimuli; and (iii) less consistency in the findings regarding structural and resting state neuroimaging, and electrophysiological measures.

Keywords: Bipolar disorder; Cognition; Endophenotype; Mood disorder; Neurocognition; Neuroimaging; Pathophysiology; Psychiatry.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Bipolar Disorder*
  • Cognition
  • Cross-Sectional Studies
  • Endophenotypes*
  • Humans
  • Neuroimaging