Cognitive deficits in first-degree relatives of bipolar patients: the use of homogeneous subgroups in the search of cognitive endophenotypes.

Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary.

Evidence for cognitive subgroups in bipolar disorder and the influence of subclinical depression and sleep disturbances.

Recent research in bipolar disorder (BD) points to the relevance and persistence of cognitive deficits even in euthymia. Up to now, the mechanisms behind why some bipolar patients (BP) do not reach their former level of cognitive performance and psychosocial functioning while others remit completely, are not understood. In this study we aimed to identify a "cognitive deficit" vs. "non-deficit" subgroup within BD by using an extensive neuropsychological test battery. The test performance of 70 euthymic outpatients (BD-I and II, recruited as a sample of convenience from our bipolar disorder programme) was compared to 70 matched, healthy controls (HC). Furthermore, we investigated the association between demographic/clinical variables and the cognitive performance of BP. As expected, our sample of euthymic BP performed significantly worse than HC in psychomotor speed, divided attention, working memory, verbal memory, word fluency and problem solving. However, 41.4% of the patients did not have any neurocognitive deficits at all, and whether or not a patient belonged to the non-deficit group was not influenced by disease severity. Instead, our results demonstrate that patients suffering from persistent sleep disturbances and sub-threshold depressive symptomatology show more severe cognitive dysfunctions. In addition, antipsychotic treatment and comorbid anxiety disorder were associated with cognitive deficits. In sum, these results suggest that a major part of cognitive impairment is due to current symptomatology, especially sleep disorder and sub-syndromal depression. Rigorous treatment of these symptoms thus might well improve cognitive deficits and, as a consequence, overall functioning in BD.