Cognitive functioning in patients with familial bipolar I disorder and their unaffected relatives MERVI ANTILA 1 *# , ANNAMARI TUULIO-HENRIKSSON 1 # , TUULA KIESEPPA ¨ 1,2 , MERVI EEROLA 1,3 , TIMO PARTONEN 1 AND JOUKO LO ¨ NNQVIST 1,2 1 Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland ; 2 Department of Psychiatry, University of Helsinki, Finland ; 3 Department of Mathematics and Statistics, University of Helsinki, Finland ABSTRACT Background. Impairments in verbal learning and memory, executive functions and attention are manifest in some euthymic patients with bipolar disorder (BPD). However, evidence is sparse on their putative role as aetiologically important genetic vulnerability markers for the disorder. This population-based study examined the cognitive functions of affected and unaffected individuals in families with BPD. The aim was to discover whether any cognitive function would indicate genetic liability to the disorder and could thus be regarded as endophenotypes of BPD. Method. A diagnostic interview and a neuropsychological test battery were administered to 32 familial bipolar I disorder patients, 40 of their unaffected first-degree relatives and 55 controls, all representing population-based samples. Results. Unaffected first-degree relatives showed impairment in psychomotor performance speed and slight impairment in executive function. Bipolar patients were impaired in verbal learning and memory compared with unaffected relatives and controls. They also differed from controls in tasks of executive functions. There were no difference between the groups in simple attention and working memory tasks. Conclusions. Impaired psychomotor performance speed and executive function may represent endophenotypes of BPD, reflecting possible underlying vulnerability to the disorder. Verbal memory impairments appear to be more related to the fully developed disorder. INTRODUCTION The presence of variable, state-dependent alter- ations in cognitive functioning during sympto- matic phases of bipolar disorder (BPD) has long been recognized. Moreover, recent studies focusing on euthymic BPD patients have demon- strated impairments in measures of executive functions, verbal learning and memory, and sus- tained attention (Bearden et al. 2001 ; Quraishi & Frangou, 2002; Clark & Goodwin, 2004; Thompson et al. 2005). Thus, cognitive impair- ment may be enduring in some bipolar patients and may present a trait rather than a state vari- able. However, little is known about the putative role of these dysfunctions as aetiologically im- portant genetic vulnerability markers for BPD. Although BPD has been shown to be highly heritable in twin, family and adoption studies from various populations (McGuffin et al. 2003 ; Kieseppa¨ et al. 2004), the search for the genetic loci of the disorder has been impeded by its complexity. Like other psychiatric disorders, BPD is thought to involve more than one gene and a complex mode of transmission (Craddock & Jones, 2001). Indicators of processes that mediate between the genotype and phenotype, * Address for correspondence : Mervi Antila, M.Psych., De- partment of Mental Health and Alcohol Research, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki 30, Finland. (Email : mervi.antila@ktl.fi) # These authors contributed equally to this work. Psychological Medicine, 2007, 37, 679–687. f 2006 Cambridge University Press doi:10.1017/S0033291706009627 First published online 21 December 2006 Printed in the United Kingdom 679