Risk For ADHD Research Articles

Evaluating the Joint Effects of Recurrent Copy Number Variants and Polygenic Scores on the Risk of Psychiatric Disorders in the iPSYCH2015 Case-Cohort Sample.

The impact of rare recurrent copy number variants (rCNVs) and polygenic background attributed to common variants, on the risk of psychiatric disorders is well-established in separate studies. However, it remains unclear how polygenic background modulates the effect of rCNVs. Using the population-representative iPSYCH2015 case-cohort sample (N=96,599), we investigated the association between absolute risk of psychiatric disorders and carriage of rCNVs and polygenic scores (PGS), as well as the interaction effect between the two on disease risk. Carriers of rCNVs with higher gene constraint scores had an increased absolute risk for autism, ADHD, and schizophrenia, but not depression, whereas an increase in PGS for each respective disorder was associated with higher absolute risk across all four disorders. Similarly, elevated absolute risks were observed with the increase of both PGS and gene constraints of rCNVs except in the case of depression. In contrast to some previous case-control studies, our joint analysis of rCNV groups and PGS revealed no indication of significant interactive effect between these two factors on disease risk. Also, we found no significant interactions of PGS with any of the most common individual rCNVs, except in the case of 16p13.11 duplication, which was found to attenuate the effect of ADHD-PGS on the absolute risk of ADHD. This study advances our understanding of the interplay between rare and common important genetic risk factors for major psychiatric disorders and sheds light on the importance of population-based samples in implementing precision medicine.

Exploring causal associations of antioxidants from supplements and diet with attention deficit/hyperactivity disorder in European populations: a Mendelian randomization analysis.

Antioxidants from both supplements and diet have been suggested to potentially reduce oxidative stress in individuals with ADHD. However, there is a lack of studies utilizing the Mendelian randomization (MR) method to explore the relationship between dietary and supplemental antioxidants with ADHD. This study employed two-sample mendelian randomization. Various specific antioxidant dietary supplements (such as coffee, green tea, herbal tea, standard tea, and red wine intake per week), along with diet-derived circulating antioxidants including Vitamin C (ascorbate), Vitamin E (α-tocopherol), Vitamin E (γ-tocopherol), carotene, Vitamin A (retinol), zinc, and selenium (N = 2,603-428,860), were linked to independent single nucleotide polymorphisms (SNPs). Data on ADHD was gathered from six sources, comprising 246,888 participants. The primary analytical method utilized was inverse variance weighting (IVW), with sensitivity analysis conducted to assess the robustness of the main findings. In different diagnostic periods for ADHD, we found that only green tea intake among the antioxidants was significantly associated with a reduced risk of ADHD in males (OR: 0.977, CI: 0.963-0.990, p < 0.001, FDR = 0.065), with no evidence of pleiotropy or heterogeneity observed in the results. Additionally, a nominal causal association was found between green tea intake and childhood ADHD (OR: 0.989, 95% CI: 0.979-0.998, p = 0.023, FDR = 0.843). No causal relationships were detected between the intake of other antioxidant-rich diets and ADHD. Our study found a significant inverse association between green tea intake and male ADHD, suggesting that higher green tea consumption may reduce ADHD risk in males. Further research is needed to explore optimal doses and underlying mechanisms.

Association of Parental Prenatal Mental Health on Offspring Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis.

Parental prenatal mood and anxiety disorders (PMAD) are linked to child neurodevelopmental disorders (NDDs), but evaluations of the magnitude and mechanisms of this association are limited. This study estimates the strength of the association and whether it is impacted by genetic and environmental factors. A systematic search of PubMed, CENTRAL, PsycINFO, OVID, and Google Scholar was performed for articles published from January 1988 to January 2024. Of 2,170 articles screened, 64 met the inclusion criteria. Meta-analyses were conducted on 20 studies, and 44 were included in the narrative synthesis. We conducted random-effects meta-analyses, along with tests for heterogeneity (I2) and publication bias (Egger's test). The review followed PRISMA and MOOSE guidelines. Maternal PMADs were associated with a significantly increased risk of ADHD (OR 1.91, 95% CI 1.45-2.52) and ASD (OR 1.57, 95% CI 1.37-1.81) in children. Paternal PMADs were also associated with the risk of NDDs, with combined odds for ASD and ADHD (OR 1.24, 95% CI 1.15-1.34). Several studies suggested that the link between parental PMADs and offspring NDDs might be impacted by both genetic and environmental factors, including the impact of ongoing parental depression on child behavior. Parental PMADs are significantly associated with an increased risk of NDDs in children. These associations may be influenced by both genetic predispositions and environmental factors. Understanding these pathways is important for informing interventions aimed at mitigating mental health risks in families and supporting child development.

Establishing machine learning prediction model for psychosocial and environmental risk of ADHD

Establishing machine learning prediction model for psychosocial and environmental risk of ADHD

Acetaminophen use during pregnancy was not linked to autism, ADHD, or intellectual disability in offspring.

Ahlqvist VH, Sjöqvist H, Dalman C, et al. Acetaminophen use during pregnancy and children's risk of autism, ADHD, and intellectual disability. JAMA. 2024;331:1205-1214. 38592388.

Association between genetic risk of melatonin secretion and attention deficit hyperactivity disorder

Sleep problems are common in individuals with ADHD; however, the exact underlying mechanism is unknown. I Data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research (N = 27,076), the Taiwan Biobank (N = 2373) and the Hamamatsu Birth Cohort for Mothers and Children (N = 726) were used for analysis. Linkage disequilibrium score-based genetic correlation showed a genetic correlation between melatonin secretion and ADHD diagnosis (rg[SD] = -0.134 [0.012], P < 0.001). Polygenic risk score analyses revealed that genetic variants related to melatonin secretion were associated with ADHD symptoms (beta [SD] = -0.077[0.033], P = 0.019). Dysregulation of melatonin secretion may be associated with the risk of ADHD.

Cognitive disengagement syndrome and attention deficit hyperactivity disorder: An examination of relationships with alexithymia and emotion regulation difficulties

Cognitive disengagement syndrome (CDS) and ADHD are considered distinct but interrelated constructs. This study aimed to investigate the prevalence of elevated CDS symptoms and increased ADHD risk in the general population, and their relationships with emotion regulation difficulty (ERD) and alexithymia. Out of 1166 participants, 142 with known psychiatric conditions were excluded, resulting in 1024 participants. Participants completed various scales including Adult ADHD Self-Report Screening Scale for DSM-5 (ASRS-5), Barkley Adult Sluggish Cognitive Tempo (SCT) Scale, Difficulties in Emotion Regulation Scale-Short Form (DERS-16), and the Toronto Alexithymia Scale (TAS-20). Four groups were formed based on Barkley and ASRS-5 scores: Group 1) No elevated CDS symptoms and Low risk of ADHD, Group 2) No elevated CDS symptoms and Increased risk of ADHD, Group 3) Elevated CDS symptoms and Low risk of ADHD, Group 4) Elevated CDS symptoms and Increased risk of ADHD. Elevated CDS symptoms was found in 10% of participants, and increased ADHD risk in 9.2%. Among probable ADHD cases, 40% had elevated CDS symptoms, while 60% of elevated CDS symptoms cases had increased ADHD risk. Group 4 (elevated CDS symptoms and increased risk of ADHD) had the highest ERD and alexithymia scores, while Group 1(no elevated CDS symptoms and low risk of ADHD) had the lowest. Regression analyses showed that CDS scores predicted ERD (47%) and alexithymia (32%) better than ADHD scores (ERD: 36%, alexithymia: 23%). CDS and ADHD appear as significant concepts that could be involved in the etiology of ERD and alexithymia.

Absence of Causal Relationship Between Levels of Unsaturated Fatty Acids and ADHD: Evidence From Mendelian Randomization Study

Objective: Previous research suggests a potential link between unsaturated fatty acids (UFAs) and ADHD, but the causal relationship remains uncertain. This study aims to investigate the causal association between ADHD and UFAs using Mendelian randomization (MR) analysis. Methods: Summary data from genome-wide association studies were used to estimate the concentration of circulating UFAs, including Monounsaturated Fatty Acids (MUFAs), Polyunsaturated Fatty Acids (PUFAs), Omega-3 PUFAs, Omega-6 PUFAs, Linoleic Acid (LA), and Docosahexaenoic Acid (DHA). Data from the Psychiatric Genomics Consortium, including both childhood and adult ADHD, were respectively used to examine the relationship between genetically predicted UFAs levels and ADHD. Various MR methods, including Inverse-variance weighted (IVW), MR Pleiotropy RESidual Sum and Outlier, MR-Egger, weighted median, and weighted mode, were employed to assess heterogeneity and pleiotropy. Results: The IVW revealed only nominal evidence suggesting a potential causal relationship between genetically predicted PUFAs (OR = 0.92, 95% CI [0.85, 0.99], p = .031), Omega-6 PUFAs (OR = 0.90, 95% CI [0.83, 0.98], p = .020), and LA levels (OR = 0.90, 95% CI [0.82, 0.98], p = .021) with childhood ADHD risk. However, after false discovery rate correction, the p-values for PUFAs, Omega-6 PUFAs, and LA levels all exceeded the threshold for significance. For adult ADHD, we did not find any significant associations between the six circulating UFA levels and adult ADHD. Conclusion: Our findings do not support a causal relationship between UFAs levels and ADHD. This suggests that UFAs supplements may not be effective in improving ADHD symptoms and importantly, it appears that UFAs levels may not have a long-term effect on ADHD.

The mediating role of parent stress in the relationship between children’s emotion dysregulation and ADHD risk: a pilot study

Despite the well-known link between earlier children’s emotional dysregulation and their high risk of developing later ADHD symptoms, few studies investigated the relationships between positive and negative emotion dysregulation, on the one hand, and ADHD symptoms, on the other one, via parent stress. This pilot study aimed to investigate the mediating role of parental stress on the relationship between children’s positive and negative emotion dysregulation and ADHD risk indices. A sample of 62 children (Female = 38.2%; M = 65.90 months; SD = 3.8) was rated by one of their parents (i.e., mothers), using the subscales of the Italian Temperament Questionnaire (QUIT; i.e., positive and negative emotionality) and the subscales of Conners’ Parent Rating Scale-Revised (CPRS; i.e., hyperactivity and inattentions deficit). Furthermore, parents reported their stress levels by completing the Parenting Stress Index—Short Form (PSI-SF) self-report. Findings show the mediating role of parental stress on the relationship between negative emotion dysregulation and both measures of ADHD symptoms (hyperactivity/impulsivity and inattention deficit).

Attention-Deficit Hyperactivity Disorder Symptoms in Adults Diagnosed with Multiple Sclerosis: Prevalence and Correlates.

Background: The relationship between adult ADHD symptoms in People with Multiple Sclerosis (PwMS) is understudied. This study aimed to answer two questions: are PwMS more likely to experience higher ADHD symptoms versus healthy subjects? And what are the correlates of severe ADHD symptoms in PwMS? Methods: This study followed a cross-sectional design with predefined inclusion criteria. The Adult ADHD Self-Report Scale-V1.1 (ASRS) was used to assess the ADHD symptoms severity. Results: Data were analyzed from 171 PwMS and 200 controls. Regression analysis revealed that PwMS were at a significantly (B = 3.05, t = 2.24, 95% CI = 0.37-5.73, p = 0.02) higher risk to report higher ADHD scores versus controls. In addition, PwMS with relapses in the last 6 months and PwMS reporting smartphone addiction were at a significantly higher risk for severe ADHD (B = 7.19, t = 269, 95% CI = 1.91-12.48, p = 0.008) and (B = 9.18, t = 3.47, 95% CI = 3.97-14.41, p = 0.001), respectively. In conclusion, diagnosis with MS in our study was identified as a risk for higher ADHD symptoms. Conclusions: Further research is required to establish this relationship, and holistic medical and psychological interventions are required to improve the cognitive status of PwMS.

Gene-gene and gene-environmental interaction of dopaminergic system genes in Pakistani children with attention deficit hyperactivity disorder

BackgroundAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder influenced by genetic and environmental factors. This study examined the specific gene variants, dopamine transporter 1 (DAT1) rs6350, dopamine receptor D3 (DRD3) rs6280, dopamine receptor D2 (DRD2) rs6277, and catechol-O-methyltransferase (COMT) rs4633, in relation to ADHD among Pakistani children by exploring the potential gene-gene and gene-environment interactions. MethodsA total of 100 cases of ADHD and 100 healthy children were recruited. The tetra-primer amplification refractory mutation system (ARMS) assays were designed for genotyping the selected variants in both groups, and their association with ADHD was determined in different genetic models. Gene-gene and gene-environmental interactions were determined by the multifactor dimensionality reduction (MDR) method. ResultsThe DAT1 rs6350 SNV AA genotype showed a significantly increased risk for ADHD in the codominant and recessive models. Conversely, the AG genotype demonstrated a protective factor for ADHD in the codominant and overdominant models. The DRD3 rs6280 T allele exhibited a decreased risk for ADHD, and the TT genotype showed a reduced risk in the recessive and log-additive models. No association between the DRD2 rs6277 and COMT rs4633 SNVs with ADHD was found in our population. The MDR analysis of the best three-fold interaction model showed redundancy between DAT1 rs6350 and DRD3 rs6280; however, the risk was increased with the gender variable, which showed a weak synergistic interaction with these SNVs. ConclusionGenes associated with dopaminergic neurotransmission may contribute to the occurrence of ADHD. Furthermore, gene-gene and gene-environmental interactions may increase ADHD susceptibility.

The Influence of Prenatal Environmental Factors on the Risk and Development of ADHD: Insights from Epidemiological and Neurodevelopmental Research - Review

The Influence of Prenatal Environmental Factors on the Risk and Development of ADHD: Insights from Epidemiological and Neurodevelopmental Research - Review

Physical Fitness and Risk of Mental Disorders in Children and Adolescents

With the rising prevalence of mental disorders among children and adolescents, identifying modifiable associations is critical. To examine the association between physical fitness and mental disorder risks. This nationwide cohort study used data from the Taiwan National Student Fitness Tests and National Health Insurance Research Databases from January 1, 2009 to December 31, 2019. Participants were divided into 2 cohorts targeting anxiety and depression (1 996 633 participants) and attention-deficit/hyperactivity disorder (ADHD; 1 920 596 participants). Participants were aged 10 to 11 years at study entry and followed up for at least 3 years, had a nearly equal gender distribution, and an average follow-up of 6 years. Data were analyzed from October 2022 to February 2024. Assessments of physical fitness included cardiorespiratory fitness (CF), muscular endurance (ME), muscular power (MP), and flexibility, measured through an 800-m run time, bent-leg curl-ups, standing broad jump, and sit-and-reach test, respectively. Kaplan-Meier method calculated the cumulative incidence of anxiety, depression, and ADHD across fitness quartiles. Additionally, multivariable Cox proportional hazards models were used that included all 4 fitness components and explored sex and income as modifiers. The anxiety and depression cohort had 1 996 633 participants (1 035 411 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years), while the ADHD cohort had 1 920 596 (975 568 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years). Cumulative incidence of mental disorders was lower among participants in better-performing fitness quartiles, suggesting a dose-dependent association. Gender-specific analyses, controlling for confounders, revealed that improved CF, indicated by a 30-second decrease in run times, was associated with reduced risks of anxiety, depression, and ADHD in female participants, and lower risks of anxiety and ADHD in male participants (adjusted hazard ratio [aHR] for ADHD risk for female participants, 0.92; 95% CI, 0.90-0.94; P < .001; for male participants, 0.93; 95% CI, 0.92-0.94; P < .001). Enhanced ME, marked by an increase of 5 curl-ups per minute, was associated with decreased risks of depression and ADHD in female participants, and lower anxiety and ADHD risks in male participants (aHR for ADHD risk for female participants, 0.94; 95% CI, 0.92-0.97; P < .001; for male participants, 0.96; 95% CI, 0.95-0.97; P < .001). Improved MP, reflected by a 20-cm increase in jump distance, was associated with reduced risks of anxiety and ADHD in female participants and reduced anxiety, depression, and ADHD in male participants (aHR for ADHD risk for female participants, 0.95; 95% CI, 0.91-1.00; P = .04; for male participants, 0.96; 95% CI, 0.94-0.99; P = .001). This study highlights the potential protective role of cardiorespiratory fitness, muscular endurance, and muscular power in preventing the onset of mental disorders. It warrants further investigation of the effectiveness of physical fitness programs as a preventive measure for mental disorders among children and adolescents.

Paracetamol use in pregnancy does not increase risk of ADHD and autism

Paracetamol use in pregnancy does not increase risk of ADHD and autism

Prenatal cannabis use increases risk of ADHD and autism in children

Prenatal cannabis use increases risk of ADHD and autism in children

Development and validation of a nomogram prediction model for ADHD in children based on individual, family, and social factors

ObjectivesA reliable, user-friendly, and multidimensional prediction tool can help to identify children at high risk for ADHD and facilitate early recognition and family management of ADHD. We aimed to develop and validate a risk nomogram for ADHD in children aged 3–17 years in the United States based on clinical manifestations and complex environments. MethodsA total of 141,356 cases were collected for the prediction model. Another 54,444 cases from a new data set were utilized for performing independent external validation. The LASSO regression was used to control possible variables. A final risk nomogram for ADHD was established based on logistic regression, and the discrimination and calibration of the established nomogram were evaluated by bootstrapping with 1000 resamples. ResultsA final risk nomogram for ADHD was established based on 13 independent predictors, including behavioral problems, learning disabilities, age, intellectual disabilities, anxiety symptoms, gender, premature birth, maternal age at childbirth, parent-child interaction patterns, etc. The C-index of this model was 0.887 in the training set, and 0.862 in the validation set. Internal and external validation proved that the model was reliable. ConclusionsA nomogram, a statistical prediction tool that assesses individualized ADHD risk for children is helpful for the early identification of children at high risk for ADHD and the construction of a conceptual model of society-family-school collaborative diagnosis, treatment, and management of ADHD.

Gestational epigenetic age and ADHD symptoms in childhood: a prospective, multi-cohort study.

Epigenetic age acceleration (EAA), defined as the difference between chronological age and epigenetically predicted age, was calculated from multiple gestational epigenetic clocks (Bohlin, EPIC overlap, and Knight) using DNA methylation levels from cord blood in three large population-based birth cohorts: the Generation R Study (The Netherlands), the Avon Longitudinal Study of Parents and Children (United Kingdom), and the Norwegian Mother, Father and Child Cohort Study (Norway). We hypothesized that a lower EAA associates prospectively with increased ADHD symptoms. We tested our hypotheses in these three cohorts and meta-analyzed the results (n = 3383). We replicated previous research on the association betweengestational age (GA) and ADHD. Both clinically measured gestational age as well as epigenetic age measures at birth were negatively associated with ADHD symptoms at ages 5-7 years (clinical GA: β = -0.04, p < 0.001, Bohlin: β = -0.05, p = 0.01; EPIC overlap: β = -0.05, p = 0.01; Knight: β = -0.01, p = 0.26). Raw EAA (difference between clinical and epigenetically estimated gestational age) was positively associated with ADHD in our main model, whereas residual EAA (raw EAA corrected for clinical gestational age) was not associated with ADHD symptoms across cohorts. Overall, findings support a link between lower gestational age (either measured clinically or using epigenetic-derived estimates) and ADHD symptoms. Epigenetic age acceleration does not, however, add unique information about ADHD risk independent of clinically estimated gestational age at birth.

Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study

BackgroundGrowing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. MethodsThis study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer’s disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. ResultsEach 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00–2.02), ADHD (1.51, 1.15–1.98), schizophrenia (1.47, 1.15–1.87), and AD (1.57, 1.16–2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. ConclusionsThis study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Association Between Maternal Diabetes and ChildhoodNeurodevelopmental Disorders

IntroductionThe prevalence of metabolic disorders is rising, diabetes prevalence doubled during 1990-2017. In 2020, 7.8% of US pregnancies were complicated by Gestational Diabetes Mellitus (GDM). Our aim is to assess the impact this increase has on childhood developmental disorders and understand the link between maternal metabolic disorders and neurodevelopmental disorders in children with focus on Autism Spectrum Disorder (ASD) and ADHD.ObjectivesOur aim is to assess the impact this increase has on childhood developmental disorders and understand the link between maternal metabolic disorders and neurodevelopmental disorders in children with focus on Autism Spectrum Disorder (ASD) and ADHD.MethodsA literature search was conducted using medical subject heading (MeSH) terms in PubMed, database from Jan 1 2014 to Feb 15, 2023. Only large-scale (n&gt;20,000) were reviewed. A total of 3 articles were included in our final qualitative synthesis review.ResultsAn increased rate of ASD and ADHD are observed in children of mothers with insulin resistance, demonstrated by Type 2 Diabetes (T2DM) and GDM (Kuan-Ru Chen, et al.). T2DM had the strongest association with ASA and ADHD when looking at other neurodevelopmental disorders (Chen, et al.). GDM severity correlates to increased risk of ADHD (Xiang, et al.). Maternal obesity as a risk factor for ASA and ADHD has confidence intervals in the same ranges as immune dysregulatory disorders including Asthma and Autoimmune disorders (Woolfenden, et al.).ConclusionsPathomechanism of neurodevelopmental disorders involves maternal oxidative stress and inflammation. Maternal T2DM and obesity are pro-inflammatory states that can be targeted as modifiable risk factors of ASD and ADHD in children. Preconception metabolic optimization and tight glycemic control in pregnancy are two ways clinicians can start to address the rates of rising ASD and ADHD.Disclosure of InterestNone Declared

Aggressiveness in Italian Children with ADHD: MAOA Gene Polymorphism Involvement.

ADHD is a neurodevelopmental disorder that children and adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls. We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p = 0.02 and p = 0.03, respectively), whereas the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p = 0.0002 and p = 0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highlighted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness, suggesting that these genotypes may be protective towards specific changes in behavior (p = 0.05). Interestingly, an increase in the GG genotype of rs6323 (p = 0.01) and a decrease in GT genotype (p = 0.0005) was also found in patients without aggressive behavior compared to controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help in the early detection of patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.