Influence of Serotonin Transporter SLC6A4 Genotype on the Effect of Psychosocial Stress on Cognitive Performance: An Exploratory Pilot Study.

BACKGROUND AND OBJECTIVE: Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams. METHODS: In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants' cognitive response to stress across genotypes. RESULTS: A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition. CONCLUSIONS: Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.

Development of the N1-P2 auditory evoked response to amplitude rise time and rate of formant transition of speech sounds.

We investigated the development of weighting strategies for acoustic cues by examining the morphology of the N1-P2 auditory evoked potential (AEP) to changes in amplitude rise time (ART) and rate of formant transition (RFT) of consonant-vowel (CV) pairs in 4-6-year olds and adults. In the AEP session, individuals listened passively to the CVs /ba/, /wa/, and a /ba/ with a superimposed slower-rising /wa/ envelope (/ba/(wa)). In the behavioral session, individuals listened to the same stimuli and judged whether they heard a /ba/ or /wa/. We hypothesized that a developmental shift in weighting strategies should be reflected in a change in the morphology of the N1-P2 AEP. In 6-year olds and adults, the N1-P2 amplitude at the vertex reflected a change in RFT but not in ART. In contrast, in the 4-5-year olds, the vertex N1-P2 did not show specificity to changes in ART or RFT. In all groups, the N1-P2 amplitude at channel C4 (right hemisphere) reflected a change in ART but not in RFT. Behaviorally, 6-year olds and adults predominately utilized RFT cues (classified /ba/(wa) as /ba/) during phonetic judgments, as opposed to 4-5-year olds which utilized both cues equally. Our findings suggest that both ART and RFT are encoded in the auditory cortex, but an N1-P2 shift toward the vertex following age 4-5 indicates a shift toward an adult-like weighting strategy, such that, to utilize RFT to a greater extent.

Effect of propranolol on functional connectivity in autism spectrum disorder--a pilot study.

A decrease in interaction between brain regions is observed in individuals with autism spectrum disorder (ASD), which is believed to be related to restricted neural network access in ASD. Propranolol, a beta-adrenergic antagonist, has revealed benefit during performance of tasks involving flexibility of access to networks, a benefit also seen in ASD. Our goal was to determine the effect of propranolol on functional connectivity in ASD during a verbal decision making task as compared to nadolol, thereby accounting for the potential spurious fMRI effects due to peripheral hemodynamic effects of propranolol. Ten ASD subjects underwent fMRI scans after administration of placebo, propranolol or nadolol, while performing a phonological decision making task. Comparison of functional connectivity between pre-defined ROI-pairs revealed a significant increase with propranolol compared to nadolol, suggesting a potential imaging marker for the cognitive effects of propranolol in ASD.

Effect of propranolol on verbal problem solving in autism spectrum disorder.

The noradrenergic system modulates performance on tasks dependent on semantic and associative network flexibility (NF) in individuals without neurodevelopmental diagnoses in experiments using a beta-adrenergic antagonist, propranolol. Some studies suggest drugs decreasing noradrenergic activity are beneficial in ASD. In individuals without neurodevelopmental diagnoses, propranolol is beneficial only for difficult NF-dependent problems. However, in populations with altered noradrenergic regulation, propranolol also benefits performance for simple problems. Due to decreased flexibility of access to networks in ASD, we wished to examine the effect of propranolol on NF in ASD. ASD subjects benefited from propranolol on simple anagrams, whereas control subjects were impaired by propranolol. Further study will be necessary to confirm this finding in a larger sample and to compare clinical response with cognitive response to propranolol.