Is processing speed a valid neurocognitive endophenotype in bipolar disorder? Evidence from a longitudinal, family study.

BACKGROUND: Substantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed. METHODS: A sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs. RESULTS: At T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05). CONCLUSIONS: The results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings.

Neurocognitive endophenotypes in schizophrenia and bipolar disorder: A systematic review of longitudinal family studies.

Although there is substantial evidence supporting the existence of neurocognitive impairment in patients diagnosed with schizophrenia (SZ) and bipolar disorder (BD), few studies have explored the field from an endophenotypic perspective. The present systematic review sought to identify longitudinal family studies exploring suitable neurocognitive endophenotypes in unaffected relatives of patients with SZ and/or BD. Following the PRISMA statement, only five follow-up studies met the inclusion criteria, comprising 79 SZ patients, 159 SZ unaffected relatives of SZ, 131 BD patients, 77 unaffected relatives of BD, and 248 controls. Verbal memory, auditory attention, face memory and emotion processing were found as putative endophenotypic candidates for SZ, whereas this strategy identified none for BD. Substantial heterogeneity and lack of standardization in global neurocognitive assessment within this area should be pointed out; nevertheless, several candidate endophenotypes were identified for SZ, except for executive impairment.