title: The search for neuroimaging and cognitive endophenotypes: A critical systematic review of studies involving unaffected first-degree relatives of individuals with bipolar disorder.
abstract: 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.
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: Kamilla@miskowiak.dk.
authors.forename: Kamilla W
authors.initials: KW
authors.lastname: Miskowiak
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Hanne L
authors.initials: HL
authors.lastname: Kjærstad
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Iselin
authors.initials: I
authors.lastname: Meluken
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jeff Zarp
authors.initials: JZ
authors.lastname: Petersen
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Beatriz R
authors.initials: BR
authors.lastname: Maciel
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: Cristiano A
authors.initials: CA
authors.lastname: Köhler
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: Copenhagen Affective Disorder Research Centre, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Lars V
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: Translational Psychiatry Research Group and Department of Clinical Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
authors.forename: André F
authors.initials: AF
authors.lastname: Carvalho
mesh_terms: D001714:Bipolar Disorder; D003071:Cognition; D003430:Cross-Sectional Studies; D058068:Endophenotypes; D006801:Humans; D059906:Neuroimaging
keywords: Bipolar disorder; Cognition; Endophenotype; Mood disorder; Neurocognition; Neuroimaging; Pathophysiology; Psychiatry