Abstract: BACKGROUND: Few studies have examined Manual Motor Speed (MMS) in bipolar disorder (BD). The aim of this longitudinal, family study was to explore whether dysfunctional MMS represents a neurocognitive endophenotype of BD. METHODS: A sample of 291 subjects, including 131 BD patients, 77 healthy first-degree relatives (BD-Rel), and 83 genetically-unrelated healthy controls (HC), was assessed with the Finger-Tapping Test (FTT) on three occasions over a 5-year period. Dependence of FTT on participants´ age was removed by means of a lineal model of HC samples, while correcting simultaneously the time and learning effect. Differences between groups were evaluated with an ANOVA test. RESULTS: The patients' performance was significantly worse than that of HC over time (p?0.006), and these deficits remained when non-euthymic BD patients (n=9) were excluded from analysis. Some significant differences between BD patients and BD-Rel (p?0.037) and between BD-Rel and HC (p?0.033) were found, but they tended to disappear as time progressed (p?0.057). Performance of the BD-Rel group was intermediate to that of BD and HC. Most sociodemographic and clinical variables did not affect these results in patients. (p?0.1). However, treatment with carbamazepine and benzodiazepines may exert a iatrogenic effect on MMS performance (p?0.006). LIMITATIONS: Only right-handed subjects were included in this study. Substantial attrition over time was detected. CONCLUSIONS: There were significant differences between the patients´ MMS performance and that of healthy relatives and controls, regardless of most clinical and sociodemographic variables. Dysfunctional MMS could be considered an endophenotype of BD. Further studies are needed to rule out possible iatrogenic effects of some psychopharmacological treatments.

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