No abstract

Considerable evidence demonstrates that neuropsychological deficits are prevalent in bipolar disorder during both acute episodes and euthymia. However, it is less clear whether these cognitive disturbances are state- or trait-related. We here present the first longitudinal study employing a within-subject pre- and post-testing examining acutely admitted bipolar patients (BP) in depression or mania and during euthymia, aiming to identify cognitive performance from acute illness to remission. Cognitive performance was measured during acute episodes and repeated after at least 3 months of remission. To do so, 55 BP (35 depressed, 20 hypo-/manic) and 55 healthy controls (HC) were tested with a neuropsychological test battery (attention, working memory, verbal memory, executive functioning). The results showed global impairments in acutely ill BP compared to HC: depressed patients showed a characteristic psychomotor slowing, while manic patients had severe deficits in executive functioning. Twenty-nine remitted BP could be measured in the follow-up (dropout rate 48 %), whose cognitive functions partially recovered, whereas working memory and verbal memory were still impaired. However, we found that subthreshold depressive symptoms and persisting sleep disturbances in euthymic BP were associated with reduced speed, deficits in attention and verbal memory, while working memory was correlated with psychotic symptoms (lifetime). This result indicates working memory as trait related for a subgroup of BP with psychotic symptoms. In contrast, attention and verbal memory are negatively influenced by state factors like residual symptoms, which should be more considered as possible confounders in the search of cognitive endophenotypes in remitted BP.

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.

Recent research in bipolar disorder points at the relevance and persistence of cognitive deficits in bipolar patients (BPD) even beyond acute episodes of depression or mania. Impairments were found in attention, processing speed, memory and executive functioning. Up to now, the mechanisms, why some BPD do not reach their former level of cognitive performance and psychosocial functioning, while others are remitted completely, is not understood. In this study we aimed to identify a’deficit vs. nondeficit subgroup’ within BPD. For this purpose, we investigated the association between demographic and disease specific variables and the cognitive performance of BPD. The test performance of 70 remitted outpatients (Bipolar-Type I and II) was compared to 70 healthy controls (HC). Participants performed an extensive neuropsychological test battery.As expected our sample of euthymic BPD performed significantly worse than HCs in three of eight cognitive domains, namely Planning, Cognitive Flexibility and Divided Attention. In line with previous findings, more than a half of the euthymic BPD did not have any neuropsychological deficits. We found no significant correlations between test performance and clinical variables. But interestingly, we revealed significant associations between subthreshold depressive symptomatology and psychomotor slowing, impaired long term and working memory.In sum, these results suggest the presence of cognitive subgroups in bipolar disorder. However, we found no evidence of underlying etiologies: Clinical characteristics seem to have no influence. However, our results indicate that cognitive deficits found in euthymic BPD could result from a subdepressive syndrome and not per se by disease characteristics.