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World J Biol Psychiatry. 2015;16(8):625-34. doi: 10.3109/15622975.2015.1067371. Epub 2015 Oct 1.

Variation in serotonin neurotransmission genes affects neural activation during response inhibition in adolescents and young adults with ADHD and healthy controls.

Author information

a University Medical Center Groningen, Department of Psychiatry , University of Groningen , Groningen , The Netherlands.
b Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University , Nijmegen , The Netherlands.
c Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Human Genetics Department , Nijmegen , The Netherlands.
d Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour , Department of Cognitive Neuroscience , Nijmegen , The Netherlands.
e Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry , Nijmegen , The Netherlands.
f Department of Clinical Neuropsychology , VU University Amsterdam , Amsterdam , The Netherlands.
g Karakter Child and Adolescent Psychiatry University Center , Nijmegen , The Netherlands.



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.


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.


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.


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.


5HT; ADHD; endophenotype; response inhibition; siblings

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