Differences in cognitive deficits in individuals with subthreshold syndromes with and without family history of bipolar disorder

Little is known about the development of cognitive deficits prior to the official onset of bipolar disorder (BP). The aim of this study was to investigate neurocognitive performance in two early stages of BP. This high-risk design study recruited a group of offspring of parents with BP (n = 58), aged 8-28 years. Based on the subthreshold syndromes, the "unaffected" offspring were further divided into high-risk (HR) and ultra-high-risk (UHR) stages. For comparison, a group of individuals with subthreshold symptoms but without family history of psychiatric disorder (n = 17) and 48 healthy controls (HCs) were included. The MATRICS Consensus Cognitive Battery (MCCB) and Tower of London task were applied to assess neuropsychological performance. The HR offspring performed significantly poorer on verbal learning and memory when compared with HCs, indicating that the deficits may serve as neurocognitive endophenotypes for BP. Deficits in working memory, visual-spatial memory, and cognitive planning were observed in the UHR offspring when compared with HCs, suggestive of risk of developing BP. The deficits observed in the UHR offspring were absent in the individuals with subthreshold symptoms without psychiatric family history. Our data suggest that cognitive deficits become apparent prior to the official onset of BP, with specific deficits observable in different early stages. These results nonetheless are based on small sample size and a cross-sectional design. Given this and the heterogeneity of bipolar disorders, these findings should be interpreted cautiously and require replication.