<b>Introduction:</b> Studies have documented both executive functions (EF) impairment in children with Attention Deficit / Hyperactivity Disorders (ADHD) and Theory of Mind (ToM), yielding mixed results, possibly because of a variety of tasks used, all requiring different levels of language skills.<b>Aim:</b> To investigate the relationship between ToM and EF with non-language-based tasks.<b>Methods:</b> Thirty ADHD (7-9 years old) were compared to thirty controls (age and IQ matched).
A total of 110 adult patients with ASD (n=61) or ADHD (n=49) with or without a lifetime history of SUD participated in a study in which we genotyped polymorphisms in five known candidate genes for (one of) the disorders, i.e. the 5HTTLPR in SLC6A4/5-HTT, rs1800497 (TaqIA C>T) in DRD2, rs7794745 in CNTNAP2, rs1843809 in TPH2, and rs6565113 in CDH13.
Among previously identified ADHD candidate genes, prominent association signals were observed for SLC9A9 (rs1393072, OR=1.46, 95% CI = 1.21-1.77, p=9.95E-05) and TPH2 (rs17110690, OR = 1.38, 95% CI = 1.14-1.66, p=8.31E-04).
Five markers in three genes, DDC, TPH2, and SLC6A2 showed nominal association (P < 0.01) with ADHD combined subtype when restricted to maternal or paternal transmission only.
Here, we appraise the genetic and neurobiological evidence to illustrate the critical role of TPH2 in central 5-HT system function and in the pathophysiology of a wide spectrum of disorders of cognitive control and emotion regulation, ranging from depression to attention-deficit/hyperactivity disorder (ADHD), a phenotype commonly associated with difficulties in the control of emotion and with a high co-morbidity of depression.
In conclusion, in the single largest ADHD genetic study of TPH1 and TPH2 variants presented to date (n = 3,559 individuals), we did not find consistent evidence for a substantial effect of common genetic variants on persistent ADHD.
In that respect, several variants of the tryptophan hydroxylase gene (TPH2), which codes for the rate-limiting enzyme in the biosynthesis of serotonin (5-HT), have been associated with ADHD.
Our results link potentially functional TPH2 variations to the pathophysiology of ADHD, and further support the relevance of 5-HT in disorders related to altered motor activity and cognitive processes.
The two most common TPH2 eight locus haplotypes were in a Yin Yang configuration and the Yang haplotype was the risk haplotype for both DSM IV ADHD and deficits in neuropsychological performance.
We investigated the association of serotonin the 1A receptor C-1019G single nucleotide polymorphism (HTR1A C-1019G SNP) and tryptophan hydroxylase 2 gene -703G/T (TPH2-703G/T) SNP with ADHD.