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

Abstract

Rationale: 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.

Methods: Thirty-two healthy subjects (25 males, mean age 26.0 years, range 19-37) underwent positron emission tomography using the SERT ligand [(11)C]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.

Results: 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.

Conclusions: 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.