Association of DRD4 polymorphism with severity of oppositional defiant disorder,separation anxiety disorder and repetitive behaviors in children with autism spectrum disorder

The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother‐ and teacher‐completed DSM‐IV‐referenced rating scale. Partial eta‐squared (ηp²) was used to gauge the magnitude of group differences: 0.01?0.06 = small, 0.06?0.14 = moderate and > 0.14 = large. Children who were 7‐repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers’ (ηp² = 0.10) and teachers’ (ηp² = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7‐repeat allele carriers also obtained more severe maternal ratings of tics (ηp² = 0.07) and obsessions–compulsions (ηp² = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ηp² = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers’ ratings of oppositional behavior and mothers’ ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples.     

Association of dopamine gene variants,emotion dysregulation and ADHD in autism spectrum disorder

The aim of the present study was to evaluate the association of dopaminergic gene variants with emotion dysregulation (EMD) and attention-deficit/hyperactivity disorder (ADHD) symptoms in children with autism spectrum disorder (ASD). Three dopamine transporter gene (SLC6A3/DAT1) polymorphisms (intron8 5/6 VNTR, 3′-UTR 9/10 VNTR, rs27072 in the 3′-UTR) and one dopamine D2 receptor gene (DRD2) variant (rs2283265) were selected for genotyping based on à priori evidence of regulatory activity or, in the case of DAT1 9/10 VNTR, commonly reported associations with ADHD. A sample of 110 children with ASD was assessed with a rigorously validated DSM-IV-referenced rating scale. Global EMD severity (parents’ ratings) was associated with DAT1 intron8 (ηp² = .063) and rs2283265 (ηp² = .044). Findings for DAT1 intron8 were also significant for two EMD subscales, generalized anxiety (ηp² = .065) and depression (ηp² = .059), and for DRD2 rs2283265, depression (ηp² = .053). DRD2 rs2283265 was associated with teachers’ global ratings of ADHD (ηp² = .052). DAT1 intron8 was associated with parent-rated hyperactivity (ηp² = .045) and both DAT1 9/10 VNTR (ηp² = .105) and DRD2 rs2283265 (ηp² = .069) were associated with teacher-rated inattention. These findings suggest that dopaminergic gene polymorphisms may modulate EMD and ADHD symptoms in children with ASD but require replication with larger independent samples.     

Psychological mindedness and symptom reduction after psychotherapy in a heterogeneous psychiatric sample

Background

Psychological mindedness (PM) has been claimed to be beneficial for outcome of various forms of psychotherapy. The purpose of this study was to investigate the influence of PM on the therapy results of a psychiatric patient sample with heterogeneous psychological symptoms.

Methods

Participants were 110 patients with different diagnoses who were hospitalized at the Center for Psychological Recovery (Rosmalen, Netherlands). Before and after treatment, they were asked to complete the Balanced Index of Psychological Mindedness and the Symptom Checklist-90.

Results

Baseline PM was not associated with a decrease in symptom scores (F_8,73 < 1.0; P > .20; partial η² < 0.10). However, PM increased over the course of the intervention (F_2,84 = 43.54; P < .001; η² = 0.51) and larger increases in the insight component of PM were associated with larger decreases on 6 of 8 symptom scores (F_8,70 = 3.55; P < .005; partial η² = 0.29).

Conclusions

These results suggest that although a high PM is not a prerequisite for successful cognitive behavioral therapy, an increase in insight is associated with better outcome.     

Role of genetic polymorphisms of the dopaminergic system in Parkinson's disease patients with impulse control disorders

BackgroundThe mechanisms underlying the development of impulse control disorders (ICDs) like compulsive gambling, buying, sexual, and eating behaviors in Parkinson’s disease (PD) are debated. We assessed whether allelic variants of dopamine D2 receptors (DRD2), catechol-O-methyltransferase (COMT) and dopamine transporter (DAT) were associated with the development of ICDs in PD.MethodWe enrolled 89 idiopathic PD patients (48 without ICDs and 41 with ICDs). All patients were screened with the Minnesota Impulsive Disorders Interview (MIDI) and fulfilled DSM-IV criteria for the ICD positive cohort. Differences in the frequency of the genotypes between ICDs and non-ICDs groups were assessed using the χ² test.ResultsGenotyping was performed for variants of the DRD2 Taq1A (rs1800497), COMT Val¹⁵⁸Met (rs4680), DAT1 (3′ UTR 40 bp VNTR). Variants of DRD2 Taq1A, COMT and DAT1 were not associated with the risk of developing ICDs.ConclusionIn our study, there were no differences in the frequency of variant of DRD2 Taq1A, COMT and DAT1 between the two groups. Polymorphisms of dopaminergic genes do not play a relevant role in the development of ICD in PD suggesting that ICD originate from inability to filter inappropriate behaviors triggered by dopaminergic therapy.     

The influence of genetic variants on striatal dopamine transporter and D2 receptor binding after TBI

Dopamine (DA) neurotransmission influences cognition and recovery after traumatic brain injury (TBI). We explored whether functional genetic variants affecting the DA transporter (DAT) and D2 receptor (DRD2) impacted in vivo dopaminergic binding with positron emission tomography (PET) using [¹¹C]βCFT and [¹¹C]raclopride. We examined subjects with moderate/severe TBI (N=12) ∼1 year post injury and similarly matched healthy controls (N=13). The variable number of tandem repeat polymorphism within the DAT gene and the TaqI restriction fragment length polymorphism near the DRD2 gene were assessed. TBI subjects had age-adjusted DAT-binding reductions in the caudate, putamen, and ventral striatum, and modestly increased D2 binding in ventral striatum versus controls. Despite small sample sizes, multivariate analysis showed lower caudate and putamen DAT binding among DAT 9-allele carriers and DRD2 A2/A2 homozygotes with TBI versus controls with the same genotype. Among TBI subjects, 9-allele carriers had lower caudate and putamen binding than 10/10 homozygotes. This PET study suggests a hypodopaminergic environment and altered DRD2 autoreceptor DAT interactions that may influence DA transmission after TBI. Future work will relate these findings to cognitive performance; future studies are required to determine how DRD2/DAT1 genotype and DA-ligand binding are associated with neurostimulant response and TBI recovery.     

Interaction between serotonin 5-HT2A receptor gene and dopamine transporter (DAT1) gene polymorphisms influences personality trait of persistence in Austrian Caucasians

We examined 89 normal volunteers using Cloninger's Temperament and Character Inventory (TCI). Genotyping the 102T/C polymorphism of the serotonin 5HT2A receptor gene and the ser9gly polymorphism in exon 1 of the dopamine D3 receptor (DRD3) gene was performed using PCR-RFLP, whereas the dopamine transporter (DAT1) gene variable number of tandem repeats (VNTR) polymorphism was investigated using PCR amplification followed by electrophoresis in an 8% acrylamide gel with a set of size markers. We found a nominally significant association between gender and harm avoidance (P=0.017; women showing higher scores). There was no association of either DAT1, DRD3 or 5HT2A alleles or genotypes with any dimension of the TCI applying Kruskal–Wallis rank-sum tests. Comparing homozygote and heterozygote DAT1 genotypes, we found higher novelty seeking scores in homozygotes (P=0.054). We further found a nominally significant interaction between DAT1 and 5HT2A homo-/heterozygous gene variants (P=0.0071; DAT1 and 5HT2A genotypes P value of 0.05), performing multivariate analysis of variance (MANOVA). Examining the temperamental TCI subscales, this interaction was associated with persistence (genotypes: P=0.004; homo-/heterozygous gene variants: P=0.0004). We conclude that an interaction between DAT1 and 5HT2A genes might influence the temperamental personality trait persistence.     

DAT1 methylation is associated with methylphenidate response on oppositional and hyperactive-impulsive symptoms in children and adolescents with ADHD

Objectives: To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD).

Methods: One hundred and eleven DSM-IV defined ADHD Chinese Han children were recruited. Inattention, hyperactivity–impulsivity and oppositional symptoms were evaluated by the Swanson, Nolan and Pelham–IV–parent rating scale (SNAP-IV-P) at baseline and 6 weeks after MPH treatment. DNA methylation of CpG sites in the promoter sequences of DAT1 and DRD4 was examined for association with treatment response.

Results: Greater improvement on the SNAP-IV-P total score and percentage change from baseline score were both significantly correlated with DAT1 methylation (rho?=?0.222, P?=?.019 and rho?=??0.203, P?=?.032, respectively). A secondary analysis demonstrated that the effect of DAT1 methylation on symptom response was primarily related to the percentage change in oppositional symptoms (rho?=??0.242; P?=?.012), with a smaller significant effect on hyperactivity–impulsivity (rho?=??0.192; P?=?.045). No significant correlation was found between the treatment effect on inattention and DAT1 methylation (rho?=??0.101; P?=?.292). No significant correlation was observed between mean DRD4 methylation and measures of treatment outcome or baseline symptoms.

Conclusions: Our findings provide initial evidence for the involvement of the epigenetic alterations of DAT1 in modulating the response to MPH treatment in ADHD, primarily on oppositional and hyperactive-impulsive symptoms.     

Exploring the Relationship Between Movement Disorders and Physical Activity in Patients With Schizophrenia: An Actigraphy Study

Low physical activity (PA) and sedentary behavior (SB) are major contributors to mental health burden and increased somatic comorbidity and mortality in people with schizophrenia and related psychoses. Movement disorders are highly prevalent in schizophrenia populations and are related to impaired functioning and poor clinical outcome. However, the relationship between movement disorders and PA and SB has remained largely unexplored. Therefore, we aimed to examine the relationship between movement disorders (akathisia, dyskinesia, dystonia, and parkinsonism) and PA and SB in 216 patients with schizophrenia and related psychoses. Actigraphy, the St. Hans Rating Scale for extrapyramidal syndromes, and psychopathological ratings (PANSS-r) were applied. Data were analyzed using multiple linear regression, adjusting for sex, age, negative symptoms, and defined daily dose of prescribed antipsychotics. Parkinsonism was significantly associated with decreased PA (β = −0.21, P < .01) and increased SB (β = 0.26, P < .001). For dystonia, only the relationship with SB was significant (β = 0.15, P < .05). Akathisia was associated with more PA (β = 0.14, P < .05) and less SB (β = −0.15, P < .05). For dyskinesia, the relationships were non-significant. In a prediction model, akathisia, dystonia, parkinsonism and age significantly predicted PA (F(5,209) = 16.6, P < .001, R²_Adjusted = 0.27) and SB (F(4,210) = 13.4, P < .001, R²_Adjusted = 0.19). These findings suggest that movement disorders, in particular parkinsonism, are associated with reduced PA and increased SB in patients with psychotic disorders. Future studies should take movement disorders into account when examining PA and SB, to establish the clinical value of movement disorders in activating people with psychotic disorders to improve their mental and somatic health.     

360° Video virtual reality exposure therapy for public speaking anxiety: A randomized controlled trial

Public speaking anxiety (PSA) is a prevalent condition which is highly interrelated with social anxiety. PSA can be effectively treated with exposure therapy. Virtual reality exposure therapy (VRET) is increasingly being explored as a novel and cost-effective mode of treatment. No previous randomized controlled trial has examined whether stand-alone 360° video VRET is an effective intervention for treating PSA and interrelated disorder relevant fears. Further, studies have not explored whether 360° video content influences VRET outcomes. Participants with high PSA (n = 51) were randomly allocated to: 360° video VRET incorporating stimuli of audiences (360°Audience) (n = 17), 360° video VRET incorporating stimuli of empty rooms (360°Empty) (n = 16) and no treatment control (n = 18). Outcomes were measured over five time-points. Mixed ANOVA revealed a significant interaction between time and intervention group for PSA, social anxiety and fear of negative evaluation (FNE). Within-group analysis demonstrated there was a significant pre-intervention to post-intervention reduction across measures for both 360° video VRET groups: PSA 360°Audience ($\eta$ _p² = .90, p<.001), 360°Empty ($\eta$ _p² = .71, p < .001); social anxiety 360°Audience ($\eta$ _p² = .49, p=.002), 360°Empty ($\eta$ _p² = .39, p = .009); FNE 360°Audience ($\eta$ _p² = .59, p<.001), 360°Empty ($\eta$ _p² = .43, p = .006). Active intervention participants showed significant improvement from pre-intervention to 10-week follow-up on all measures. Findings illustrate that 360° video VRET is an efficacious way to significantly reduce PSA, social anxiety and FNE.     

<Emphasis Type="Italic">DAT1</Emphasis> and <Emphasis Type="Italic">DRD4</Emphasis> genes involved in key dimensions of adult ADHD

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3′UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10^?4) and trait anger scores (p = 7.66 × 10^?4). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.     

Motor-cognitive effects of a computerized game-based training method in people with dementia: a randomized controlled trial

ABSTRACT

Objectives: To examine the effects of a computerized, game-based training on motor-cognitive performances, the transfer of training effects on untrained tasks, and the sustainability of training gains in people with dementia.

Method: Ninety-nine individuals with a mean age of 82.9 (5.8) and dementia participated in a 10-week randomized controlled trial with three-month follow-up. The intervention group (IG) received a motor-cognitive training on (Physiomat®) including concurrent dual-tasks of balance control with cognitive demands (Physiomat®-Trail Making Tasks (PTMTs)). The control group (CG) performed non-specific, low-intensity exercises. Duration and accuracy at different complexity levels of trained and untrained PTMTs and the number of successfully performed tasks (PTMT score) were assessed.

Results: Physiomat® training significantly improved the duration and accuracy at almost all complexity levels of trained (P ≤ 0.001–0.047, η_p² = 0.065–0.589) and untrained PTMTs (P < 0.001–0.005, η_p² = 0.073–0.459). Significant effects were also found for the PTMT score of trained (P < 0.001, η_p² = 0.211) and untrained PTMTs (P < 0.001, η_p² = 0.184). Training gains were partly sustained at follow-up.

Conclusion: Physiomat® is feasible and has the potential to sustainably improve motor-cognitive performances in people with dementia.     

Dissociative symptoms in patients with schizophrenia: relationships with childhood trauma and psychotic symptoms

ObjectiveThis study sought to examine the stability of dissociative symptoms in patients with schizophrenia spectrum disorders as well as relationships between psychotic symptoms, childhood trauma, and dissociation.MethodOne hundred forty-five patients with schizophrenia spectrum disorders (72% schizophrenia, 67% men) were examined at admission to inpatient treatment and 3 weeks later using the Positive and Negative Syndrome Scale, the Childhood Trauma Questionnaire, and the Dissociative Experiences Scale.ResultsDissociative symptoms significantly decreased over time (mean, 19.2 vs 14.1; P < .001). The best predictor of dissociative symptoms at admission was the Positive and Negative Syndrome Scale positive subscale (F_{inc 3,64} = 3.66, P = .017), whereas childhood sexual abuse best predicted dissociation when patients were stabilized (F_{inc 10,80} = 2.00, P = .044).ConclusionDissociative symptoms in patients with schizophrenia spectrum disorders are related to childhood trauma. Dissociation seems to be state dependent in this diagnostic group. Moreover, diagnostic interviews, in addition to the Dissociative Experiences Scale, should be considered to avoid measurement artifacts.     

Temperaments mediate suicide risk and psychopathology among patients with bipolar disorders

BackgroundSeveral studies have demonstrated that bipolar II (BD-II) disorder represents a quite common, distinct form of major mood disorders that should be separated from bipolar I (BD-I) disorder. The aims of this cross-sectional study were to assess temperament and clinical differences between patients with BD-I and BD-II disorders and to assess whether temperament traits are good predictors of hopelessness in patients with bipolar disorder, a variable highly associated with suicidal behavior and ideation.MethodParticipants were 216 consecutive inpatients (97 men and 119 women) with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), BD who were admitted to the Sant'Andrea Hospital's psychiatric ward in Rome (Italy). Patients completed the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego—Autoquestionnaire, the Beck Hopelessness Scale (BHS), the Mini International Neuropsychiatric Interview (MINI), and the Gotland Scale of Male Depression.ResultsPatients with BD-II had higher scores on the BHS (9.78 ± 5.37 vs 6.87 ± 4.69; t_143.59 = ?3.94; P < .001) than patients with BD-I. Hopelessness was associated with the individual pattern of temperament traits (ie, the relative balance of hyperthymic vs cyclothymic-irritable-anxious-dysthmic). Furthermore, patients with higher hopelessness (compared with those with lower levels of hopelessness) reported more frequently moderate to severe depression (87.1% vs 38.9%; P < .001) and higher MINI suicidal risk.ConclusionTemperaments are important predictors both of suicide risk and psychopathology and may be used in clinical practice for better delivery of appropriate care to patients with bipolar disorders.     

Candidate system analysis in ADHD: Evaluation of nine genes involved in dopaminergic neurotransmission identifies association with DRD1

Abstract

Objectives. Several pharmacological and genetic studies support the involvement of the dopamine neurotransmitter system in the aetiology of attention-deficit hyperactivity disorder (ADHD). Based on this information we evaluated the contribution to ADHD of nine genes involved in dopaminergic neurotransmission (DRD1, DRD2, DRD3, DRD4, DRD5, DAT1, TH, DBH and COMT). Methods. We genotyped a total of 61 tagging single nucleotide polymorphisms (SNPs) in a sample of 533 ADHD patients (322 children and 211 adults), 533 sex-matched unrelated controls and additional 196 nuclear ADHD families from Spain. Results. The single- and multiple-marker analysis in both population and family-based approaches provided preliminary evidence for the contribution of DRD1 to combined-type ADHD in children (P = 8.8e-04; OR = 1.50 (1.18–1.90) and P = 0.0061; OR = 1.73 (1.23–2.45)) but not in adults. Subsequently, we tested positive results for replication in an independent sample of 353 German families with combined-type ADHD children and replicated the initial association between DRD1 and childhood ADHD (P = 8.4e-05; OR = 3.67 (2.04–6.63)). Conclusions: The replication of the association between DRD1 and ADHD in two European cohorts highlights the validity of our finding and supports the involvement of DRD1 in childhood ADHD.     

Potential role for peripheral nerve stimulation on learning and long-term memory: A comparison of alternating and direct current stimulations

BackgroundIn the past decade, a rising interest in transcranial electrical stimulation has emerged owing to its advantageous capacity to facilitate the extraction of casual links between neuromodulation and the obtained behavioral effects in cognitive performance. However, an insufficient number of direct comparative studies between transcranial alternating current stimulation (tACS) and transcranial direct current stimulation (tDCS) effects on associative memory have caused optimal parameters and procedural application to remain undefined.ObjectiveThe current study aimed to comparatively investigate the effects of tDCS and tACS applied to the occipital nerve (ON), targeting the locus coeruleus, on associative memory performance.MethodsWe employed a randomized, double-blind, two-visit, active-controlled study design. 85 cognitively normal adults were assigned to receive either active ON-tDCS, 40 Hz ON-tACS, sham ON-tDCS, or 1 Hz ON-tACS during encoding of a 50-word Swahili-English associative memory recall task. To evaluate the effects of electrical stimulation, we measured the cumulative rate of learning on Day 1 and to assess possible long-term effects, we measured the number of words recalled on Day 7.ResultsResults presented two notable findings: (1) participants who received 40 Hz ON-tACS learned significantly more words on Day 1 (F_3,81 = 4.37, p = .007, η² = 0.14), and (2) participants who received 40 Hz ON-tACS or active ON-tDCS recalled significantly more words on Day 7 (F_3,81 = 11.08, p < .001, η² = 0.29).ConclusionsThe evidence from this study alludes to 40 Hz ON-tACS and active ON-tDCS inducing distinct behavioral effects, whereby 40 Hz ON-tACS generated an effect during memory encoding via enhanced attention, however, active ON-tDCS elicited an offline effect transpiring during consolidation. Further neuroimaging studies are needed to validate these findings and proposed mechanisms of action.     

Driving Behaviors in Adults with Autism Spectrum Disorders

This pilot study investigated driving history and driving behaviors between adults diagnosed with autism spectrum disorders (ASD) as compared to non-ASD adult drivers. Seventy-eight licensed drivers with ASD and 94 non-ASD comparison participants completed the Driver Behavior Questionnaire. Drivers with ASD endorsed significantly lower ratings of their ability to drive, and higher numbers of traffic accidents and citations relative to non-ASD drivers. Drivers with ASD also endorsed significantly greater numbers of difficulties on the following subscales: intentional violations, F(1, 162) = 6.15, p = .01, η _p ²  = .04; mistakes, F(1, 162) = 10.15, p = .002, η _p ²  = .06; and slips/lapses, F(1, 162) = 11.33, p = .001, η _p ²  = .07. These findings suggest that individuals with ASD who are current drivers may experience more difficulties in driving behaviors and engage in more problematic driving behaviors relative to non-ASD drivers.     

The Protective Impact of Telemedicine on Persons With Dementia and Their Caregivers During the COVID-19 Pandemic

ObjectivesSocial distancing under the COVID-19 pandemic has restricted access to community services for older adults with neurocognitive disorder (NCD) and their caregivers. Telehealth is a viable alternative to face-to-face service delivery. Telephone calls alone, however, may be insufficient. Here, we evaluated whether supplementary telehealth via video-conferencing platforms could bring additional benefits to care-recipient with NCD and their spousal caregivers at home.ParticipantsSixty older adults NCD-and-caregiver dyads were recruited through an activity center.Design, InterventionThe impact of additional services delivered to both care-recipient and caregiver through video conference (n = 30) was compared with telehealth targeted at caregivers by telephone only (n = 30), over 4 weeks in a pretest–post-test design. Interviews and questionnaires were conducted at baseline and study's end.Measurements, ResultsSupplementary telemedicine had averted the deterioration in the Montreal Cognitive Assessment evident in the telephone-only group (η_p² = 0.50). It also reversed the falling trend in quality of life observed in the telephone only group (QoL-AD, η_p² = 0.23). Varying degrees of improvements in physical and mental health (Short-Form 36 v2), perceived burden (Zarit Burden Interview Scale) and self-efficacy (Revised Caregiving Self-Efficacy Scale) were observed among caregivers in the video-conferencing group, which were absent in the telephone-only group (η_p² = 0.23–0.51).ConclusionTelemedicine by video conference was associated with improved resilience and wellbeing to both people with NCD and their caregivers at home. The benefits were visible already after 4 weeks and unmatched by telephone alone. Video conference as the modus operandi of telehmedicine beyond the context of pandemic-related social distancing should be considered.     

Molecular imaging genetics of methylphenidate response in ADHD and substance use comorbidity

Purpose: Attention‐deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs) are highly comorbid and may share a genetic vulnerability. Methylphenidate (MPH), a dopamine transporter (DAT) blocker, is an effective drug for most ADHD patients. Although dopamine D4 receptor (DRD4) and dopamine transporter (DAT1) genes have a role in both disorders, little is known about how these genes influence brain response to MPH in individuals with ADHD/SUDs. The goal of this study was to evaluate whether ADHD risk alleles at DRD4 and DAT1 genes could predict the change in striatal DAT occupancy after treatment with MPH in adolescents with ADHD/SUDs. Methods: Seventeen adolescents with ADHD/SUDs underwent a SPECT scan with [Tc^99m]TRODAT‐1 at baseline and after three weeks on MPH. Caudate and putamen DAT binding potential was calculated. Comparisons on DAT changes were made according to the subjects' genotype. Results: The combination of both DRD4 7‐repeat allele (7R) and homozygosity for the DAT1 10‐repeat allele (10/10) was significantly associated with a reduced DAT change after MPH treatment in right and left caudate and putamen, even adjusting the results for potential confounders (P ≤ 0.02; R² from 0.50 to 0.56). Conclusions: In patients with ADHD/SUDs, combined DRD4 7R and DAT1 10/10 could index MPH reduced DAT occupancy. This might be important for clinical trials, in terms of better understanding individual variability in treatment response. Synapse 2011. © 2010 Wiley‐Liss, Inc.     

Dopaminergic system genes in childhood aggression: Possible role for DRD2

Abstract

Excessive or deficient levels of extracellular dopamine have been hypothesized to contribute to a broad spectrum of mood, motor, and thought abnormalities, and dopaminergic system genes have been implicated in aggressive behaviour from animal and human studies. Objective. We examined selected members of the dopaminergic system genes for association with child aggression. Method. We analyzed polymorphisms in the dopamine transporter DAT1/SLC6A3, dopamine receptor DRD2, and DRD4 genes in our sample of pervasive childhood aggression consisting of 144 cases paired with 144 healthy controls, matched for sex and ethnicity. Results. Aggressive children were significantly more likely to have the at least one copy of the G allele for the DRD2 A-241G polymorphism (genotypic P=0.02; allelic P=0.01). The DRD2 rs1079598 CC genotype was overrepresented in aggressive children compared to controls (genotype P=0.04). The DRD2 TaqIA T allele (P=0.01) and the TT genotype (P=0.01) were also significantly overrepresented in aggressive children. Conclusions. Our preliminary results suggest that three polymorphisms in DRD2 are associated with childhood aggression. Future studies are required to replicate the current results and to further explore the relationship between the dopamine system and aggressive behaviour in children.     

A preliminary report of the dopamine receptor D4 and the dopamine transporter 1 gene polymorphism and its association with attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is one of the most prevalent childhood-onset psychiatric syndromes affecting 5%–10% of school-age children worldwide. Distortions in the catecholaminergic system seem to be responsible for this condition. Within this system there are several candidate genes, the dopamine receptor D₄ (DRD4) and the dopamine transporter 1 (DAT1), with common polymorphism which might be associated with ADHD. We performed a family based association study with 36 trios and 19 parent proband pairs. All diagnoses were confirmed by the “Hypescheme” diagnostic computer program. In this study we did not observe an association of ADHD with DRD4 and DAT1 polymorphism neither by the haplotype relative risk (HRR) method nor by the transmission disequilibrium test (TdT) method. The odds ratio for the DRD4 7-allele was 1.01 and 0.94 for both statistical tests, respectively, and the respective odds ratio for the DAT1 6-allele were 0.91 and 0.88.