Cognitive impairment in schizoaffective disorder: a comparison with non-psychotic bipolar and healthy subjects

Objective: Only a few studies have examined specifically the neuropsychological performance of schizoaffective patients. Method: The sample consisted of 34 euthymic DSM‐IV schizoaffective patients, who were compared with 41 euthymic bipolar patients without history of psychotic symptoms and 35 healthy controls. Euthymia was defined by a score of 6 or less at the Young Mania Rating Scale and a score of 8 or less at the Hamilton Depression Rating Scale for at least 6 months. Patients were compared with several clinical, occupational, and neuropsychological variables such as executive function, attention, verbal and visual memory and the two groups were contrasted with 35 healthy controls on cognitive performance. The three groups were compared using mancova after checking the potential role of several co‐variables. Results: Schizoaffective patients showed greater impairment than controls and bipolar patients, in several domains, including verbal memory, executive function, and attentional measures. Bipolar patients without history of psychosis performed similar to the controls except for verbal fluency. Conclusion: Schizoaffective disorder carries more neurocognitive impairment than non‐psychotic bipolar disorder and more occupational difficulties.     

Neurocognitive function in unmedicated manic and medicated euthymic pediatric bipolar patients

OBJECTIVE: A systematic evaluation of neuropsychological functioning in individuals with pediatric bipolar disorder is necessary to clarify the types of cognitive deficits that are associated with acutely ill and euthymic phases of the disorder and the effects of medication on these deficits. METHOD: Unmedicated (N=28) and medicated (N=28) pediatric bipolar patients and healthy individuals (N=28) (mean age=11.74 years, SD=2.99) completed cognitive testing. Groups were matched on age, sex, race, parental socioeconomic status, general intelligence, and single-word reading ability. A computerized neurocognitive battery and standardized neuropsychological tests were administered to assess attention, executive function, working memory, verbal memory, visual memory, visuospatial perception, and motor skills. RESULTS: Subjects with pediatric bipolar disorder, regardless of medication and illness status, showed impairments in the domains of attention, executive functioning, working memory, and verbal learning compared to healthy individuals. Also, bipolar subjects with comorbid attention deficit hyperactivity disorder (ADHD) performed worse on tasks assessing attention and executive function than patients with bipolar disorder alone. CONCLUSIONS: The absence of differences in the deficits of neurocognitive profiles between acutely ill unmedicated patients and euthymic medicated patients suggests that these impairments are trait-like characteristics of pediatric bipolar disorder. The cognitive deficits found in individuals with pediatric bipolar disorder suggest significant involvement of frontal lobe systems supporting working memory and mesial temporal lobe systems supporting verbal memory, regardless of ADHD comorbidity.     

The effect of previous psychotic mood episodes on cognitive impairment in euthymic bipolar patients

OBJECTIVES: Cognitive dysfunctions in several domains were proposed to be trait markers of bipolar patients. The aim of this study was to evaluate the effect of previous psychotic features on neuropsychological measures, including sustained attention, in remitted bipolar patients. METHODS: The study participants were 40 euthymic psychotic, 25 non-psychotic bipolar I patients and 30 healthy control subjects. Participants were assessed with a battery of neuropsychological tests targeting attention, executive functions, psychomotor speed, verbal learning and memory. RESULTS: Euthymic psychotic bipolar patients performed worse than controls on most of the measures, after controlling for the confounding effects of education, age and residual symptoms. Non-psychotic patients were also impaired on tasks of attention, fluency and psychomotor speed. 'Number of Wisconsin Card Sorting Test (WCST) categories' achieved was the only measure on which psychotic patients performed significantly worse compared to non-psychotic patients. Differences among patient groups were not explained by illness severity measures. The duration of illness was related to slowness in psychomotor speed tasks. Verbal memory deficits may be related to serum lithium levels and age of onset of disease. CONCLUSIONS: Deficits in cognitive flexibility may be a candidate for being a trait marker of psychotic features among bipolar patients. However, verbal fluency, psychomotor speed and sustained attention deficits may be candidates for vulnerability indicators of bipolar disorder in general.     

Neuropsychological profile in bipolar disorder: a preliminary study of monotherapy lithium-treated euthymic bipolar patients evaluated at a 2-year interval

Objective: To investigate the cognitive impairment of a sample of euthymic bipolar patients treated with lithium monotherapy at baseline in a 2‐year longitudinal study. Method: Fifteen DSM‐IV‐TR bipolar out‐patients and 15 healthy‐matched controls were cognitively assessed twice over a 2‐year follow‐up. All patients underwent lithium monotherapy on the first evaluation, and they were euthymic in both evaluations. Cognitive assessment was performed by means of a neuropsychological test battery tapping into the main cognitive domains (executive function, attention, processing speed, verbal memory and visual memory). Results: Repeated measures multivariate analysis of variance showed that the bipolar disorder group was cognitively impaired in the executive domain, attention and processing speed, and such deficits were maintained over time. Conclusion: Our results showed that executive dysfunction is the main long‐term neuropsychological deficit of bipolar disorder. Also, the persistence of these deficits did not seem to be influenced by any clinical or pharmacological variables.     

Clinical and neurocognitive correlates of insight in patients with bipolar I disorder in remission

Objective: The relationship between insight and neurocognition in bipolar disorder has not been clearly established. Method: A neuropsychological battery assessing attention, mental control, perceptual‐motor skills, executive functions, verbal fluency and abstraction, and visuo‐spatial attention was administered to 50 bipolar remitted patients and 50 healthy controls. Insight was assessed with the Scale to Assess Unawareness of Mental Disorder. Results: Patients presented significantly worse neurocognitive performance. Insight was impaired in 60% of patients, and age, educational level, manic symptoms, age of disease onset, number of admissions, and performance on several neurocognitive tests correlated significantly with insight. A regression model revealed that age and Trail Making Test part B (TMT‐B) performance accounted for 32% of the variance in overall illness awareness, while performance on the TMT‐B alone accounted for 28% of the variance. Conclusion: Impaired insight and neurocognitive dysfunction seem to be present in euthymic bipolar patients. Insight in bipolar disorder may be partially dependent on intact neurocognition.     

Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome

OBJECTIVE: Cognitive impairment in bipolar disorder may be a stable characteristic of the illness, although discrepancies have emerged with regard to what dysfunctions remain during remission periods. The aim of this study was to ascertain whether euthymic bipolar patients would show impairment in verbal learning and memory and in executive functions compared with healthy controls. Secondly, to establish if there was a relationship between clinical data and neuropsychological performance. METHODS: Forty euthymic bipolar patients were compared with 30 healthy controls through a battery of neuropsychological tests assessing estimated premorbid IQ, attention, verbal learning and memory, and frontal executive functioning. The effect of subsyndromal symptomatology was controlled. RESULTS: Remitted bipolar patients performed worse than controls in several measures of memory and executive function, after controlling for the effect of subclinical symptomatology, age and premorbid IQ. Verbal memory impairment was related to global assessment of function scores, as well as to a longer duration of illness, a higher number of manic episodes, and prior psychotic symptoms. CONCLUSIONS: Results provide evidence of neuropsychological impairment in euthymic bipolar patients, after controlling for the effect of subsyndromal depressive symptoms, suggesting verbal memory and executive dysfunctions. Cognitive impairment seems to be related to a worse clinical course and poor functional outcome.     

Neurocognitive impairment in euthymic young adults with bipolar spectrum disorder and recurrent major depressive disorder

OBJECTIVE: Patients with remitted major depressive disorder (MDD) and bipolar disorder have persistent impairments in executive function and verbal memory that may represent endophenotypic abnormalities. In this study, we examine neurocognitive function in a sample of euthymic young adults with bipolar spectrum disorder (BSD) (Can J Psychiatry 2002; 47: 125-134) and compare this to well-matched samples of young adults with recurrent MDD and controls. METHOD: Twenty-one euthymic young adult patients with BSD were compared with 42 young adult patients with MDD and 33 controls on a neuropsychological battery assessing attention, executive function and verbal memory. RESULTS: Patients with BSD were significantly more impaired than MDD patients and controls on tests of executive function and verbal memory. MDD patients did not differ significantly from controls on verbal memory function but performed less well on a test of executive function. CONCLUSION: Euthymic young adults with BSD had greater impairment on neurocognitive measures associated with prefrontal and hippocampal function than MDD patients and controls. This is a reflection of a strong bipolar diathesis in the BSD group rather than being a consequence of a more severe unipolar illness.     

Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis

OBJECTIVE: Although cognitive deficits are prominent in symptomatic patients with bipolar disorder, the extent and pattern of cognitive impairment in euthymic patients remain uncertain. METHOD: Neuropsychological studies comparing euthymic bipolar patients and healthy controls were evaluated. Across studies, effect sizes reflecting patient-control differences in task performance were computed for the 15 most frequently studied cognitive measures in the literature. RESULTS: Across the broad cognitive domains of attention/processing speed, episodic memory, and executive functioning, medium-to-large performance effect size differences were consistently observed between patients and controls, favoring the latter. Deficits were not observed on measures of vocabulary and premorbid IQ. CONCLUSION: Meta-analytic findings provide evidence of a trait-related neuropsychological deficit in bipolar disorder involving attention/processing speed, memory, and executive function. Findings are discussed with regard to potential moderators, etiologic considerations, limitations, and future directions in neuropsychological research on bipolar disorder.     

Impaired verbal memory in young adults with unipolar and bipolar depression

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course.     

Differential pattern of semantic memory organization between bipolar I and II disorders

Semantic cognition is one of the key factors in psychosocial functioning. The aim of this study was to explore the differences in pattern of semantic memory organization between euthymic patients with bipolar I and II disorders using the category fluency task. Study participants included 23 euthymic subjects with bipolar I disorder, 23 matched euthymic subjects with bipolar II disorder and 23 matched control subjects. All participants were assessed for verbal learning, recall, learning strategies, and fluency. The combined methods of hierarchical clustering and multidimensional scaling were used to compare the pattern of semantic memory organization among the three groups. Quantitative measures of verbal learning, recall, learning strategies, and fluency did not differ between the three groups. A two-cluster structure of semantic memory organization was identified for the three groups. Semantic structure was more disorganized in the bipolar I disorder group compared to the bipolar II disorder. In addition, patients with bipolar II disorder used less elaborate strategies of semantic memory organization than those of controls. Compared to healthy controls, strategies for categorization in semantic memory appear to be less knowledge-based in patients with bipolar disorders. A differential pattern of semantic memory organization between bipolar I and II disorders indicates a higher risk of cognitive abnormalities in patients with bipolar I disorder compared to patients with bipolar II disorder. Exploring qualitative nature of neuropsychological domains may provide an explanatory insight into the characteristic behaviors of patients with bipolar disorders.     

Neurocognitive impairment and psychosocial functioning in bipolar II disorder

Solé B, Bonnin CM, Torrent C, Balanzá‐Martínez V, Tabarés‐Seisdedos R, Popovic D, Martínez‐Arán A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder. Objective: There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD‐II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD‐II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. Method: Forty‐three BD‐II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. Results: BD‐II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. Conclusion: This report provides further evidence that euthymic BD‐II patients present cognitive impairment which may impact psychosocial functioning.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

Cognitive function and serum levels of brain-derived neurotrophic factor in patients with bipolar disorder

Objectives:  Brain-derived neurotrophic factor (BDNF) is an important contributor to the pathophysiology of bipolar disorder (BD), and abnormalities in the BDNF-signaling system may be implicated in the cognitive decline observed in BD patients. We aimed to investigate serum BDNF levels in BD patients and its relation to neurocognitive function.
Methods:  We measured serum BDNF levels using an enzyme-linked immunosorbent assay method in 65 euthymic type I BD patients and 50 healthy controls, and administered a neuropsychological test battery to assess attention and mental control, perceptual-motor skills, executive functions, verbal fluency and abstraction, visuospatial attention, and memory.
Results:  We found no significant differences regarding serum BDNF levels in BD patients and healthy controls. We found significant positive associations between serum BDNF levels and illness duration, and manic and depressive episodes in female BD patients only. Serum BDNF levels were lower in patients medicated with antipsychotics and/or lithium, whereas patients on valproate and/or antidepressants showed higher serum BDNF levels. Patients performed significantly worse on 11 out of 16 neurocognitive tests as compared to controls. We found a significant positive association between serum BDNF levels and a test of verbal fluency in both BD patients and controls.
Conclusions:  Present results support the hypothesis that BDNF normalizes with mood stabilization and pharmacological treatment. Our findings in young and physically healthy patients with short illness duration and few mood episodes may explain the lack of association between serum BDNF levels and neurocognitive performance, even though cognitive performance in patients was overall significantly worse as compared to healthy controls.     

One-year double-blind study of the neurocognitive efficacy of olanzapine, risperidone, and haloperidol in schizophrenia

Neurocognitive deficits in schizophrenia can reach 1 to 2 standard deviations below healthy controls. The comparative effect of typical and atypical antipsychotic medications on neurocognition is controversial, and based primarily on studies with small samples and large doses of typical comparator medications. The present study assessed neurocognitive efficacy. It was hypothesized that olanzapine treatment would improve neurocognitive deficits to a greater degree than either risperidone or haloperidol treatment. This was a double-blind, randomized, controlled, parallel study with neurocognition assessed at baseline, and 8, 24, and 52 weeks. Per protocol, the haloperidol arm was discontinued. Four hundred and fourteen inpatients or outpatients with schizophrenia and schizoaffective disorder were treated with oral olanzapine (n = 159), risperidone (n = 158), or haloperidol (n = 97). Individual domains (executive function, learning and memory, processing speed, attention/vigilance, verbal working memory, verbal fluency, motor function, and visuospatial ability) were transformed into composite scores and compared between treatment groups. At the 52-week endpoint, neurocognition significantly improved in each group (p < 0.01 for olanzapine and risperidone, p = 0.04 for haloperidol), with no significant differences between groups. Olanzapine- and risperidone-treated patients significantly (p < 0.05) improved on domains of executive function, learning/memory, processing speed, attention/vigilance, verbal working memory, and motor functions. Additionally, risperidone-treated patients improved on domains of visuospatial memory. Haloperidol-treated patients improved only on domains of learning/memory. However, patients able to remain in treatment for the entire 52 weeks benefited more from olanzapine or risperidone treatment than haloperidol treatment.     

Neurocognitive function in clinically stable men with bipolar I disorder or schizophrenia and normal control subjects.

BACKGROUND: Patients with bipolar disorder and schizophrenia have been shown to have neurocognitive deficits when compared with control subjects. The degree and pattern of impairment between psychiatric groups have rarely been compared, especially when subjects are psychiatrically stable. METHODS: Using a standard neurocognitive battery, we compared euthymic outpatients with bipolar disorder (n = 40), stable patients with schizophrenia (n = 20), and subjects with no psychiatric disorder (n = 22). The neurocognitive domains assessed included executive functioning, verbal memory, visual memory, procedural learning, visuoconstructive ability, and language functions. Effect sizes were calculated for each cognitive domain across groups. RESULTS: Stable schizophrenic subjects demonstrated a generalized cognitive impairment across most domains compared with control subjects, with average effect sizes of .9. Euthymic bipolar subjects were significantly impaired compared with control subjects only in executive functioning (Wisconsin Card Sorting Task) and verbal memory (California Verbal Learning Test) domains (effect sizes in the .8-.9 range). Performance on the executive function measures was bimodal among bipolar subjects, suggesting two subgroups: one with relatively normal and one with impaired executive functioning. No significant differences between the bipolar patient group and control subjects were observed in visuoconstructive ability, procedural learning, or language function. CONCLUSIONS: Both euthymic bipolar subjects and relatively stable schizophrenic subjects differed from control subjects in neurocognitive function. Among schizophrenic subjects, a generalized cognitive impairment was observed, and the degree of impairment was greater in the schizophrenic compared with the bipolar subjects. Subjects with bipolar disorder were impaired in two specific domains (verbal memory and executive function). Furthermore, within the bipolar group there was a subset with relatively normal executive functioning and a subset with significant impairment. Possible reasons for the persistence of these neurocognitive deficits in some subjects with bipolar disorder during periods of euthymia are reviewed.     

The neurocognitive performance of drug‐free and medicated euthymic bipolar patients do not differ

Objective: Although it is established that euthymic bipolar patients have neurocognitive deficits, the influence of medication on their cognitive performance is uncertain and requires investigation. Method: Neuropsychological tests of executive function, memory and attention were performed on 44 prospectively verified, euthymic bipolar I patients, 22 of whom were drug‐free. Residual mood symptom effects were controlled statistically using ancova . Results: Drug‐free and medicated patients differed only in delayed verbal recall (Rey AVLT list A7, drug‐free > medicated), and perseverations during the five‐point test (drug‐free > medicated). When residual mood symptoms were controlled statistically, differences between drug‐free and medicated subjects became insignificant. Medication effect sizes were modest. Significant correlations were found between residual depression scores and measures of verbal learning. Conclusion: Medications did not have any significant influence on neurocognitive performance, suggesting that neurocognitive deficits are an integral part of bipolar disorder.     

Bipolar I patients with and without a history of psychotic symptoms: Do they differ in their cognitive functioning?

Recently, many reports have consistently demonstrated cognitive deficits in patients with bipolar disorder (BD), but their relationship with symptomatology, specifically psychotic symptoms, remains unclear. Our main hypothesis was that a history of hallucinations and/or delusions in the course of BD-I is associated with severe cognitive deficits. We investigated several cognitive functions (memory, attention, verbal fluency and executive functions) in 18 BD-I patients with a history of psychotic symptoms (HPS+), 17 BD-I patients without a history of psychotic symptoms (HPS-), 33 schizophrenic patients and 26 healthy control subjects. Both groups of BD-I patients were more impaired than the normal controls in attention, verbal memory, verbal fluency and executive functions. Only HPS+ BD-I patients showed more difficulties in completing the Stroop test than nonpsychotic bipolar patients. Nevertheless, after adjustment for the effects of current psychopathology, this difference disappeared. Schizophrenic subjects showed worse performance than BD-I subjects in verbal memory and verbal fluency. These results suggest that a history of psychotic symptoms in bipolar I disorder may not be associated with more cognitive deficits. Further research on euthymic bipolar patients with and without HPS is required to confirm these findings.     

Cognitive functioning in elderly patients with early onset bipolar disorder

BACKGROUND: Very little is known about the long term cognitive sequelae of bipolar disorder. AIM: To investigate neuropsychological functioning in older euthymic persons with early onset bipolar disorder. METHOD: Fifteen older patients (age >60) with an early onset (<50 years) bipolar-I disorder in a euthymic mood were tested using a comprehensive neuropsychological test battery. Neuropsychological functioning was compared with that of a sex, age and education-matched group of 15 comparison subjects without mood disorders or memory complaints. RESULTS: Bipolar subjects scored lower than comparison subjects on selective attention, verbal memory, verbal fluency and mental effort tests. CONCLUSIONS: The findings suggest that euthymic bipolar patients are impaired across a range of cognitive domains. This could represent a trait-like cognitive disability related to the disease, as the impairments are comparable with those found in younger bipolar patients.     

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder

Kulkarni S, Jain S, Janardhan Reddy YC, Kumar KJ, Kandavel T. Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.
Bipolar Disord 2010: 12: 647–656. © 2010 The Authors.
Journal compilation © 2010 John Wiley & Sons A/S. Objectives: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. Methods: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. Results: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey’s auditory verbal learning test (RAVLT), and the Rey’s complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). Conclusions: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.     

Cognitive endophenotypes in a family with bipolar disorder with a risk locus on chromosome 4

Objectives: We studied cognitive function in high‐risk relatives belonging to a single extended family showing linkage of bipolar disorder to a locus on chromosome 4. High‐risk relatives were defined as those that carried the risk haplotype of polymorphic markers, identified in a previous linkage study. This family provided a rare opportunity to characterize a neuropsychological endophenotype in a homogeneous sample of relatives with a common genetic risk factor. Methods: Fifteen family members carrying the risk haplotype (eight diagnosed with bipolar disorder or depression and seven with no psychiatric diagnosis), unrelated patients with bipolar disorder (n = 36) and major depressive disorder (n = 40), and healthy control subjects (n = 33) were administered the California Verbal Learning Test, Verbal Fluency Test, Hayling Sentence Completion Test, and Brixton Spatial Anticipation Test to assess verbal memory, verbal fluency, and executive function. Results: Compared with healthy controls, family members carrying the risk haplotype were impaired in indices of memory and executive function. There were no significant differences between unaffected and affected haplotype‐carrying family members in any cognitive measure. Pronounced deficits in the encoding stage of verbal memory and category verbal fluency were evident in individuals with the risk haplotype. Conclusions: Verbal learning and semantic verbal fluency impairments may represent a cognitive endophenotype for both bipolar disorder and major depression in relatives of bipolar disorder patients, as impairment was also present in high‐risk relatives who had not developed any affective disorder symptoms. These findings suggest that impairment in semantic organization may be linked to the genetic aetiology of bipolar disorder.