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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. [ABSTRACT FROM AUTHOR]

The RBFOX1 gene (or A2BP1) encodes a splicing factor important for neuronal development that has been related to autism spectrum disorder and other neurodevelopmental phenotypes. Evidence suggests that this gene contributes to aggressive behavior. Suggestive associations with RBFOX1 have been identified in genome-wide association studies (GWAS) of anger, conduct disorder and aggressive behavior. Also, variants in this gene have been shown to contribute to temporal lobe volume, a brain area that is altered in several aggression phenotypes. In animals, this gene has been shown to modulate aggressive behavior in Drosophila. RBFOX1 has also been associated with canine aggression and is upregulated in mice that show increased aggression after frustration of an expected reward. Several associations as well as duplications and deletions affecting RBFOX1 have been identified in several psychiatric and neurodevelopmental disorders, often presenting aggressive behaviors. In this review, we summarize this evidence and provide new results for implicating RBFOX1 in aggressiveness. However, further studies are required to provide more detail on the contribution of this gene to this complex phenotype. [ABSTRACT FROM AUTHOR]