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Abstract
Objectives. Deficits in response inhibition have been associated with attention-deficit/hyperactivity disorder (ADHD). Given the role of serotonin in ADHD and impulsivity, we postulated that genetic variants within the serotonin pathway might influence response inhibition. Methods. We measured neural activation during stop-signal task performance in adolescents with ADHD (N = 185), their unaffected siblings (N = 111), and healthy controls (N = 124), and investigated the relationship of two serotonin gene polymorphisms (the rs6296 SNP of the HTR1B gene and HTTLPR variants of the 5-HTT gene) with the neural correlates of response inhibition. Results. The whole-brain analyses demonstrated large scale neural activation differences in the inferior and medial frontal and temporal/parietal regions of the response inhibition network between the different variants of both the HTR1B and 5HTT genes. Activation in these regions was significantly associated with stop-task performance, but not with ADHD diagnosis or severity. No associations were found between HTR1B and 5HTT variants and ADHD or ADHD-related neural activation. Conclusions. These results provide novel evidence that serotonin may play an important role in the neurobiology of response inhibition. Although response inhibition is strongly linked to ADHD, serotonin linked genetic variants associated with response inhibition and its neural correlates do not explain variance of the ADHD phenotype.
Highlights
Serotonin neurotransmission has a link with both cognitive control and impulsivity, one of the defining characteristics of attention-deficit/hyperactivity disorder (ADHD; see for a review Cools et al 2008)
Given the previously found associations between serotonin genes, impulsivity, and ADHD, the goal of the current study was to investigate the role of 5HTT and HTR1B variants on the neural correlates of response inhibition, behavioural performance, and the clinically defined ADHD phenotype in a sample of adolescents with ADHD, their unaffected siblings, and healthy controls
We investigated the effects of two genetic variants, HTTLPR in the serotonin transporter gene and rs6296 in the serotonin receptor gene HTR1B on response inhibition performance and its underlying neural activation patterns in a cohort consisting of participants with and without ADHD
Summary
Serotonin neurotransmission has a link with both cognitive control and impulsivity, one of the defining characteristics of attention-deficit/hyperactivity disorder (ADHD; see for a review Cools et al 2008). A main cognitive control function is the process of response inhibition, or the ability to withhold, delay, or alter an already initiated response. Response inhibition is associated with impulsivity (Nigg 2000) and has been extensively studied in relation to ADHD (Goos et al 2009; Crosbie et al 2013). Neural correlates of response inhibition have been reported as potential endophenotypes for ADHD, going beyond purely behavioural measures (Durston et al 2006; Van Rooij et al 2015a). Correspondence: Daan van Rooij, Donders Institute, P.O. Box 9104, 6500 HE Nijmegen,The Netherlands.
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