The role of a mineralocorticoid receptor gene functional polymorphism in the symptom dimensions of persistent ADHD

Abstract

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 5 % of school-aged children and 2.5 % of adults. Genetic studies in ADHD have pointed to genes in different neurobiological systems, with relatively small individual effects. The mineralocorticoid receptor is the main receptor involved in the initial triggering of stress response. Therefore, its encoding gene (NR3C2) is a candidate for psychiatric disorder studies, including ADHD, and behavioral phenotypes. There is evidence that the Val allele of the MRI180V polymorphism (rs5522) increases the risk of depression, attention and cognitive deficits. We investigated the possible role of the mineralocorticoid receptor gene in the symptom dimensions and susceptibility to persistent ADHD. We compared genotype and allele frequencies in 478 adult patients with ADHD and 597 controls and symptom dimensions in 449 patients and 132 controls. Diagnoses were based on the DSM-IV criteria. ADHD symptom dimensions were investigated with SNAP-IV for ADHD severity and Barkley scales for severity and impairment. Carriers of the Val allele presented higher inattention, hyperactivity/impulsivity and impairment scores, while genotype and allele frequencies did not differ between patients and controls. These results are consistent with a possible link between genetic variations in the HPA axis and inattention and hyperactivity measures.

Attention-deficit hyperactivity disorder in adults: A systematic review and meta-analysis of genetic, pharmacogenetic and biochemical studies

“…These are showed in Supplementary Table 1. 35, 48, 53, 54, 57, 60, 64, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113 In particular, among the most known, DRD5 , whose highly polymorphic dinucleotide repeat (CA) n has been the most studied in adults, three studies 54, 60, 80 were available, but Squassina et al 80 was excluded because no frequencies were reported. Ribases et al 48 investigated other polymorphisms.…”

Genetic Evidence for the Association of the Hypothalamic–Pituitary–Adrenal (HPA) Axis with ADHD and Methylphenidate Treatment Response

“…[Since the submission of the manuscript, a recent casecontrol study reported an association between the NR3C2 rs5522 SNP and symptoms of inattention and hyperactivity, with P between 0.01 and 0.05 (Kortmann et al 2012). This association was not replicated in the current study, when the number of inattention and hyperactivity items of the CBCL was used as quantitative traits in the FBAT analysis.…”

“…To the best of our knowledge, these genetic factors have not been investigated in the context of ADHD. [Since the submission of the manuscript, a study by Kortmann and colleagues reported an association between the NR3C2 rs5522 SNP and symptoms of inattention and hyperactivity, with P between 0.01-0.05 (Kortmann et al 2012). This study compared adult patients with ADHD, n = 478, to healthy controls, n = 597].…”

Corticosteroid receptor genes and childhood neglect influence susceptibility to crack/cocaine addiction and response to detoxification treatment

“…Moreover, it was shown that such allele increases salivary and plasma cortisol responses to psychosocial stressor and dexamethasone suppression test (van Leeuwen et al, 2011). The NR3C2 rs5522-Val allele was also linked to severity of attention-deficit/hyperactivity disorder (Kortmann et al, 2013), depressive symptoms in geriatric patients (Kuningas et al, 2007) and altered reward learning (Bogdan et al, 2010). Additionally, a genome wide association study (GWAS) has found a nominal association between NR3C2 rs5522 SNP and severity of smoking behavior (P ¼ 1.52EÀ05), with the Val allele increasing the number of smoked cigarettes per day (Berrettini et al, 2008).…”