Pronounced cognitive deficits following an intravenous L-tryptophan challenge in first-degree relatives of bipolar patients compared to healthy controls

Cognitive impairment has repeatedly been described in bipolar disorders (BD). Serotonin (5-hydroxXtryptophan; 5-HT) is possibly involved in these cognitive processes, more particularly in executive functions, learning, memory, and attention. The aim of this study was to investigate serotonergic vulnerability and its relation to cognitive functioning in healthy first-degree relatives of BID patients. We investigated the effects of an intravenous (i,v.) tryptophan (Trp) challenge and placebo on cognitive performance in 30 healthy first-degree relatives of bipolar patients (FH) and 15 matched controls in a double-blind crossover design, A distinction was made between relatives of type I BID patients (FH 1) and type II BID patients (FH II). Performances on planning, memory, attention, and psychomotor tasks were assessed 3 h after Trp infusion. After Trp, planning and attention were impaired in FH subjects but not in controls, Independent of Trip, FH subjects showed cognitive deficits on memory, focused and divided attention, and psychomotor performance. FH I subjects showed more pronounced cognitive impairments then FH II and controls. In all groups, Trp impaired memory and psychomotor performance significantly. In conclusions, cognitive deficits in FH following Trp may reflect a central 5-HT vulnerability in frontal brain areas, Independent of Trp, cognitive deficits in FH provide evidence for a trait marker for BID.