Neurotrophic factor‐related gene polymorphisms and adult attention deficit hyperactivity disorder (ADHD) score in a high‐risk male population

Abstract

Adult attention deficit hyperactivity disorder (ADHD) is a widely under-reported but nevertheless common condition with a clear heritable component. Several genes have been proposed to play a role in the childhood onset of this neurodevelopmental disorder; however, association studies of persistence of ADHD into adulthood have rarely been performed. Neurotrophic factors (NTFs) are known to be involved in several aspects of neuronal development and neural plasticity in adults. They have also been linked, particularly through brain-derived neurotrophic factor (BDNF) interaction with dopamine transport, to the pathophysiology of ADHD. This study compares the genotypes of six different single nucleotide polymorphisms of genes within the neurotrophin system and their possible association with adult ADHD score in 143 high-risk male subjects referred to a forensic psychiatric unit. The genes included NTF3, NTRK2 (TrkB), NTRK3 (TrkC), BDNF, and p75(NTR). While none of the SNPs showed significant association with ADHD symptoms, one polymorphism within the exon of NTF3 (rs6332) showed a trend toward an association between the A-allele and increased scores using both the retrospective childhood analysis Wender-Utah Rating Scale (WURS-k) (P = 0.05) and the adult ADHD assessment Wender-Reimherr interview (P = 0.03). This SNP is a silent mutation which might be in linkage disequilibrium with a functional risk variant for ADHD. As the association was only suggestive, however, this finding needs replication in a larger study with higher power.

Association between Neurotrophin-3 Polymorphisms and Executive Function in Japanese Patients with Amnestic Mild Cognitive Impairment and Mild Alzheimer Disease

“…Especially in patients with mild AD, the conflicting instructions score was significantly lower in the G allele carriers than in the subjects with an A/A genotype (table 4b). Such results indicating a predominance of A/A genotypes compared to G carriers with regard to neurocognition may support the results of previous studies, in which the NT-3 gene was found to be associated with the intelligence of individuals with ADHD, who exhibit neuropsychological attentional deficits linked to social cognitive impairments as core symptoms [23,24]. We could not find a significant association among the rs6489630 genotypes and executive function in patients with mild-stage AD or A-MCI.…”

“…Thus, the conflicting instructions mean score and standard deviation (SD) for the A/A group was 3.00 ± 0 (tables 1b, 4b). However, the effect sizes or statistical values were about the same as those in previous reports [23,24]. Thirdly, we used only the FAB to confirm the patients' executive dysfunction in this study.…”

“…Our results may help to elucidate the functional roles of not only the NT-3 gene, but also other neurotrophin gene polymorphisms described in previous studies [17,18,23,24]. Furthermore, elucidating the detailed associations between NT-3 gene diversity and behaviors in patients with AD will be an important task in the future.…”

“…NT-3 SNPs (rs6332 and rs6489630), which are located at chromosome 12p 13, are significantly associated with the severity of ADHD and intelligence concerning selective attentional tasks and performance execution as functional polymorphisms [23,24]. Especially, rs6332, which is a silent polymorphism, is located within Pro-NT-3 gene exon 1 [22][23][24].…”

“…NT-3 SNPs (rs6332 and rs6489630), which are located at chromosome 12p 13, are significantly associated with the severity of ADHD and intelligence concerning selective attentional tasks and performance execution as functional polymorphisms [23,24]. Especially, rs6332, which is a silent polymorphism, is located within Pro-NT-3 gene exon 1 [22][23][24]. While NT-3 has influenced synaptic neuroplasticity and neural cell survival in neurodevelopmental stages, few reports have described its neuroprotective roles in elderly subjects with dementia [16,25,26].…”