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Neurocognitive endophenotypes for bipolar disorder


  • The authors of this paper do not have any financial or other associations that might pose a conflict of interest in connection with this work.

Corresponding author: Daniel N Allen, PhD, Department of Psychology, University of Nevada, Las Vegas, Box 455030, 4505 Maryland Parkway, Las Vegas, NV 89154-5030, USA. Fax: + 1 702 895 0195; e-mail:


Objectives:  Neurocognitive deficits have been proposed as vulnerability markers or endophenotypes for the development of bipolar I disorder (BD I). However, few research studies have examined whether neurocognitive deficits also exist in first-degree relatives of individuals with BD I.

Methods:  This prospective study examined neurocognitive function in individuals with BD I, their first-degree relatives and a normal control group using a comprehensive battery of neurocognitive tests.

Results:  Results indicated that individuals with bipolar disorder and their unaffected relatives demonstrated neuropsychological deficits in comparison to the normal control group in the domains of visuospatial/constructional abilities, executive function, visual learning and memory, and motor speed. In general, the unaffected relatives demonstrated an intermediate level of performance in comparison to the normal control and bipolar group. After adjustment for mood symptoms, significant differences were present for the visuospatial/constructional, executive function, and motor domains. Individuals with bipolar disorder also demonstrated a differential right versus left hemisphere deficit with respect to neurocognitive tasks.

Conclusions:  Results suggest that deficits on specific neuropsychological tests, most notably Digit Symbol, Block Design and Judgment of Line Orientation, may be indicative of cognitive endophenotypes for bipolar disorder. Replication studies are needed to further identify these deficits as endophenotypes for BD I.

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