Cognitive function is related to fronto-striatal serotonin transporter levels - a brain PET study in young healthy subjects

Pharmacological manipulation of serotonergic neurotransmission in healthy volunteers impacts on cognitive test performance. Specifically, markers of serotonin function are associated with attention and executive functioning, long-term memory, and general cognitive ability. The serotonin transporter (SERT) protein is a key regulator in the serotonin system. We hypothesized that higher performance on tests sensitive to serotonin would be associated with higher SERT levels in specific fronto-striatal brain regions. Thirty-two healthy subjects (25 males, mean age 26.0 years, range 19-37) underwent positron emission tomography using the SERT ligand [C-11]DASB. Subjects underwent the following tests: Stroop Color Word Test, Trail Making Test B, Rey's Auditory Verbal Learning Test and Complex Figure Test, logical reasoning subtest from Intelligenz-Struktur-Test 2000 R, and a Danish version of National Adult Reading Test. We found positive associations between performance on the Stroop Color Word Test and right-sided dorsolateral prefrontal SERT binding (R (2) = 0.12, p = 0.048). Furthermore, scores of logical reasoning (correlating with IQ) and educational level associated positively with SERT binding in the caudate, most prominent on the left side (logical reasoning: R (2) = 0.34, p = 0.0026 (left), R (2) = 0.2, p = 0.022 (right), educational level: R (2) = 0.19, p = 0.012 (left), R (2) = 0.15, p = 0.027 (right)). Scores of logical reasoning also associated with left-sided ventrolateral prefrontal cortex (R (2) = 0.24, p = 0.014). There were no significant associations between SERT binding and tests of long-term episodic memory. The results imply that in healthy subjects, high SERT binding in fronto-striatal regions is associated with better performance on tasks involving executive function and logical reasoning.