Glutamate imbalance in key structure of the default mode network in adults with attention-deficit/hyperactivity disorder.

The default mode network (DMN) is atypically active in patients with ADHD, likely contributing to the inattention patterns observed in patients with the disorder. Nonetheless, magnetic resonance spectroscopy (MRS) studies have rarely targeted the posterior cingulate cortex, a key DMN region, and little is known about the biochemical setting within this network in patients with ADHD. We aimed to assess the differences in metabolite profiles of the posterior cingulate cortex-a key region of the DMN-between patients with ADHD and controls. Five brain metabolites-glutamate, inositol, N-acetyl aspartate, choline, and creatine-were measured through MRS in the posterior cingulate cortex of patients and controls in a 3.0 T scanner. Between-group comparison of neurometabolite concentrations in PCC was performed using multivariate analysis of covariance. A total of 88 patients and 44 controls were included in the analysis. Patients with ADHD showed lower levels of glutamate in the posterior cingulate cortex compared to controls (p = 0.003). Lower concentrations of glutamate in the posterior cingulate cortex suggest that a glutamatergic imbalance within the posterior cingulate cortex might play a role in the pathogenesis of ADHD. Further understanding of the causes and consequences of such glutamate decrease might help explain how some glutamate-related drug effects impact on ADHD symptomatology.

The symptomatology of Attention-Deficit/Hyperactivity Disorder and the genetic control of vitamin D levels.

OBJECTIVES: Vitamin D deficiency has been associated with psychiatric disorders and behavioral phenotypes such as Attention-Deficit/Hyperactivity Disorder (ADHD). Considering that vitamin D levels are polygenic, we aim to evaluate the overall effects of its genetic architecture on symptoms of inattention, hyperactivity, and impulsivity and on the serum levels of vitamin D in two independent samples of adults, as well as the specific effects of five relevant polymorphisms in vitamin D-related genes. METHODS: We evaluated 870 subjects from an ADHD sample (407 cases and 463 controls) and 319 subjects from an academic community (nutrigenetic sample). Vitamin D serum levels were obtained through Elisa test and genetic data by TaqMan™ allelic discrimination and Infinium PsychArray-24 BeadChip genotyping. Polygenic Scores (PGS) were calculated on PRSice2 based on the latest GWAS for Vitamin D and statistical analyses were conducted at Plink and SPSS software. RESULTS: Vitamin D PGSs were associated with inattention in the ADHD sample and with hyperactivity when inattention symptoms were included as covariates. In the nutrigenetic sample, CYP2R1 rs10741657 and DHCR7 rs12785878 were nominally associated with impulsivity and hyperactivity, respectively, and both with vitamin D levels. In the clinical sample, RXRG rs2134095 was associated with impulsivity. DISCUSSION: Our findings suggest a shared genetic architecture between vitamin D levels and ADHD symptoms, as evidenced by the associations observed with PGS and specific genes related to vitamin D levels. Interestingly, differential effects for vitamin D PGS were found in inattention and hyperactivity, which should be considered in further studies involving ADHD.

Refining patterns of MEF2C effects in white matter microstructure and psychiatric features.

Several GWAS reported Myocyte Enhancer Factor 2 C (MEF2C) gene associations with white matter microstructure and psychiatric disorders, and MEF2C involvement in pathways related to neuronal development suggests a common biological factor underlying these phenotypes. We aim to refine the MEF2C effects in the brain relying on an integrated analysis of white matter and psychiatric phenotypes in an extensively characterized sample. This study included 870 Brazilian adults (47% from an attention-deficit/hyperactivity disorder outpatient clinic) assessed through standardized psychiatric interviews, 139 of which underwent a magnetic resonance imaging scan. We evaluated variants in the MEF2C region using two approaches: 1) a gene-wide analysis, which uses the sum of polymorphism effects, and 2) SNP analyses, restricted to the independent variants within the gene. The outcomes included psychiatric phenotypes and fractional anisotropy for brain images. Results: The gene-wide analyses pointed to a nominal association between MEF2C and the Temporal Portion of the Superior Longitudinal Fasciculus (SLFTEMP). The SNP analysis identified four independent variants significantly associated with SLFTEMP and one (rs4218438) with Substance Use Disorder. Our findings showing specific associations of MEF2C variants with temporal-frontal circuitry components may help to elucidate how the MEF2C gene underlies a broad range of psychiatric phenotypes since these regions are relevant to executive and cognitive functions.

Dissecting the cross-trait effects of the FOXP2 GWAS hit on clinical and brain phenotypes in adults with ADHD.

The Forkhead box P2 (FOXP2) encodes for a transcription factor with a broad role in embryonic development. It is especially represented among GWAS hits for neurodevelopmental disorders and related traits, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, neuroticism, and risk-taking behaviors. While several functional studies are underway to understand the consequences of FOXP2 variation, this study aims to expand previous findings to clinically and genetically related phenotypes and neuroanatomical features among subjects with ADHD. The sample included 407 adults with ADHD and 463 controls. Genotyping was performed on the Infinium PsychArray-24 BeadChip, and the FOXP2 gene region was extracted. A gene-wide approach was adopted to evaluate the combined effects of FOXP2 variants (n = 311) on ADHD status, severity, comorbidities, and personality traits. Independent risk variants presenting potential functional effects were further tested for association with cortical surface areas in a subsample of cases (n = 87). The gene-wide analyses within the ADHD sample showed a significant association of the FOXP2 gene with harm avoidance (P = 0.001; PFDR = 0.015) and nominal associations with hyperactivity symptoms (P = 0.026; PFDR = 0.130) and antisocial personality disorder (P = 0.026; PFDR = 0.130). An insertion/deletion variant (rs79622555) located downstream of FOXP2 was associated with the three outcomes and nominally with the surface area of superior parietal and anterior cingulate cortices. Our results extend and refine previous GWAS findings pointing to a role of FOXP2 in several neurodevelopment-related phenotypes, mainly those involving underlying symptomatic domains of self-regulation and inhibitory control. Taken together, the available evidence may constitute promising insights into the puzzle of the FOXP2-related pathophysiology.

Emerging findings of glutamate-glutamine imbalance in the medial prefrontal cortex in attention deficit/hyperactivity disorder: systematic review and meta-analysis of spectroscopy studies.

One of the main challenges in investigating the neurobiology of ADHD is our limited capacity to study its neurochemistry in vivo. Magnetic resonance spectroscopy (MRS) estimates metabolite concentrations within the brain, but approaches and findings have been heterogeneous. To assess differences in brain metabolites between patients with ADHD and healthy controls, we searched 12 databases screening for MRS studies. Studies were divided into 'children and adolescents' and 'adults' and meta-analyses were performed for each brain region with more than five studies. The quality of studies was assessed by the Newcastle-Ottawa Scale. Thirty-three studies met our eligibility criteria, including 874 patients with ADHD. Primary analyses revealed that the right medial frontal area of children with ADHD presented higher concentrations of a composite of glutamate and glutamine (p = 0.02, SMD = 0.53). Glutamate might be implicated in pruning and neurodegenerative processes as an excitotoxin, while glutamine excess might signal a glutamate depletion that could hinder neurotrophic activity. Both neuro metabolites could be implicated in the differential cortical thinning observed in patients with ADHD across all ages. Notably, more homogeneous designs and reporting guidelines are the key factors to determine how suitable MRS is for research and, perhaps, for clinical psychiatry. Results of this meta-analysis provided an overall map of the brain regions evaluated so far, addressed the role of glutamatergic metabolites in the pathophysiology of ADHD, and pointed to new perspectives for consistent use of the tool in the field.

The course of attention-deficit/hyperactivity disorder through midlife.

The course of ADHD from childhood up to young adulthood has been characterized in several studies. However, little is known about the course of symptoms into middle age and beyond. This study aims to evaluate predictors of ADHD trajectories in midlife based on three assessments. The follow-up sample comprised 323 adults with ADHD, evaluated at baseline and seven and thirteen years later, from the average ages of 34 up to 47 years old. ADHD status at reassessments was used to characterize trajectories. Demographics, ADHD features, comorbidities, and polygenic scores for ADHD and genetically correlated psychiatric disorders were evaluated to predict ADHD trajectories. Study retention rate was 67% at T2 (n = 216) and 62% at T3 (n = 199). Data from patients evaluated three times showed that 68.8% coursed stable, 25.5% unstable, and 5.7% remission trajectory of ADHD. Women, individuals with more severe syndromes, higher frequency of comorbidities at reassessments, and genetic liability to depression present a higher probability of a stable trajectory. Our findings shed light on midlife ADHD trajectories and their gender, genomic and clinical correlates.

The neurodevelopmental nature of attention-deficit hyperactivity disorder in adults.

BACKGROUND: Population studies have suggested that most adults with attention-deficit hyperactivity disorder (ADHD) did not have the disorder in childhood, challenging the neurodevelopmental conceptualisation of ADHD. Arbitrary definitions of age at onset and lack of defined trajectories were accounted for the findings. AIMS: The objective of this study was to assess the proportion of individuals presenting with either a neurodevelopmental trajectory or late-onset disorder, and to assess risk factors associated with them. METHOD: Data of 4676 individuals from the 1993 Pelotas birth cohort at 11, 15, 18 and 22 years of age were used. Polythetic and latent class mixed model analyses were performed to define ADHD trajectories from childhood to adulthood, and characterise the neurodevelopmental or late-onset courses. Regression models were applied to assess factors associated with different trajectories. RESULTS: Classical polythetic analyses showed that 67% of those with ADHD at 22 years of age had a neurodevelopmental course of the disorder. Latent class mixed model analysis indicated that 78% of adults with ADHD had a trajectory of persistent symptoms, more common in males. The remaining adults with ADHD had an ascending symptom trajectory that occurred after puberty, with late-onset ADHD associated with female gender and higher IQ. CONCLUSIONS: Both polythetic and latent trajectories analyses provided empirical evidence supporting that the large majority of adults with ADHD had a neurodevelopmental disorder.

Attention-deficit/hyperactivity disorder has a state-dependent association with asthma: The role of systemic inflammation in a population-based birth cohort followed from childhood to adulthood.

There is a high comorbidity between attention-deficit/hyperactivity disorder (ADHD) and asthma, and inflammation has been proposed as a potential pathophysiological mechanism behind this association. Most studies conducted so far have used a cross-sectional design, and none has evaluated the prevalence of asthma symptoms in patients with ADHD followed from childhood to adulthood. We relied on data from the 1993 Pelotas birth cohort to evaluate the association between ADHD and asthma in patients with distinct patterns of incidence, persistence and remission, and to explore the potential role of inflammatory markers in the comorbidity. We analyzed data from 3281 individuals from the 1993 Pelotas birth cohort collected at birth (1993), 11 years (2004), 18 years (2011), and 22 years (2015). Subjects were first classified according to their ADHD and asthma status as early-onset (EO) persistent (positive screening for ADHD at 11 years and diagnosis of ADHD according to DSM-5, except criterion E, at either 18 or 22 years), EO-remittent (positive screening for ADHD at 11 years only), late-onset (diagnosis of ADHD according to DSM-5, except criterion E, at 18 or 22 years only), or healthy subjects (negative for both conditions in all evaluation). After controlling for confounders, significant associations were observed between EO-remittent ADHD and EO-remittent asthma (OR 1.68, 95% CI 1.11-2.55), EO-persistent ADHD and EO-persistent asthma (OR 4.33, 95% CI 1.65-11.34), and between late-onset ADHD and late-onset asthma (OR 1.86, 95% CI 1.28-2.70), suggesting a state-dependent association. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) were measured at the 18- and 22-year evaluations and compared between subjects positive for ADHD, asthma, and subjects with both or none conditions, regardless of the previously defined trajectories. Subjects with comorbid ADHD and asthma presented higher levels of IL-6 at the 18- and 22-year evaluations when compared to subjects negative for both conditions. Our results demonstrate a state-dependent association between ADHD and asthma despite underlying trajectories. Higher levels of serum IL-6 in patients with both conditions suggest that a pro-inflammatory environment might have a role in the pathophysiological mechanisms underlying the comorbidity.

Association between cognitive performance and SYT1-rs2251214 among women with cocaine use disorder.

The SNP rs2251214 of the SYT1 gene was recently associated with externalizing phenotypes, including ADHD and cocaine use disorder (CUD). Here, we investigated whether SYT1-rs2251214 could also be implicated with cognitive performance variations among women with CUD. Results showed that G homozygous (n = 146) have lower cognitive performance in the Stroop, Trail Making and Matrix Reasoning tests compared with A-allele carriers (n = 64), suggesting that rs2251214 may influence the severity of cognitive impairments in CUD.

FOXP in Tetrapoda: Intrinsically Disordered Regions, Short Linear Motifs and their evolutionary significance.

The FOXP subfamily is probably the most extensively characterized subfamily of the forkhead superfamily, playing important roles in development and homeostasis in vertebrates. Intrinsically disorder protein regions (IDRs) are protein segments that exhibit multiple physical interactions and play critical roles in various biological processes, including regulation and signaling. IDRs in proteins may play an important role in the evolvability of genetic systems. In this study, we analyzed 77 orthologous FOXP genes/proteins from Tetrapoda, regarding protein disorder content and evolutionary rate. We also predicted the number and type of short linear motifs (SLIMs) in the IDRs. Similar levels of protein disorder (approximately 70%) were found for FOXP1, FOXP2, and FOXP4. However, for FOXP3, which is shorter in length and has a more specific function, the disordered content was lower (30%). Mammals showed higher protein disorders for FOXP1 and FOXP4 than non-mammals. Specific analyses related to linear motifs in the four genes showed also a clear differentiation between FOXPs in mammals and non-mammals. We predicted for the first time the role of IDRs and SLIMs in the FOXP gene family associated with possible adaptive novelties within Tetrapoda. For instance, we found gain and loss of important phosphorylation sites in the Homo sapiens FOXP2 IDR regions, with possible implication for the evolution of human speech.

SNARE complex in developmental psychiatry: neurotransmitter exocytosis and beyond.

Multiple biological processes throughout development require intracellular vesicular trafficking, where the SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors) complex plays a major role. The core proteins forming the SNARE complex are SNAP-25 (synaptosomal-associated protein 25), VAMP (vesicle-associated membrane protein) and Syntaxins, besides its regulatory proteins, such as Synaptotagmin. Genes encoding these proteins (SNAP25, VAMP1, VAMP2, STX1A, SYT1 and SYT2) have been studied in relation to psychiatric disorders susceptibility. Here, we review physiological aspects of SNARE complex and genetic association results reported for attention deficit hyperactivity disorder, both in children and adults, autism spectrum disorders, major depressive disorder, bipolar disorder and schizophrenia. Moreover, we included findings from expression, pharmacogenetics and animal model studies regarding these clinical phenotypes. The overall scenario depicted here suggests that the SNARE complex may exert distinct roles throughout development, with age-specific effects of genetic variants in psychiatric disorders. Such perspective should be considered in future studies regarding SNARE complex genes.

Does collateral retrospective information about childhood attention-deficit/hyperactivity disorder symptoms assist in the diagnosis of attention-deficit/hyperactivity disorder in adults? Findings from a large clinical sample.

OBJECTIVES: In accordance with consolidated clinical practice, Diagnostic and Statistical Manual of Mental Disorders, 5th edition suggests a key role of collateral information in the evaluation of retrospective childhood attention-deficit/hyperactivity disorder symptoms in adults despite poor evidence supporting its use. This study aims to assess the incremental value of collateral information on the presence of childhood attention-deficit/hyperactivity disorder symptoms when evaluating adults with attention-deficit/hyperactivity disorder. METHODS: Adult patients with attention-deficit/hyperactivity disorder (n = 449) and non-attention-deficit/hyperactivity disorder subjects (n = 143) underwent an extensive clinical assessment based on Diagnostic and Statistical Manual of Mental Disorders, 4th edition criteria. For patients, retrospective collateral information regarding childhood attention-deficit/hyperactivity disorder was obtained and used to sort them into two groups: agreement (n = 277) and disagreement (n = 172) between self- and collateral reports. We compared demographic, clinical and response to treatment profiles among groups to test the relevance of collateral information on the specific issue of childhood attention-deficit/hyperactivity disorder symptoms. RESULTS: Both attention-deficit/hyperactivity disorder groups had higher rates of several comorbidities (oppositional defiant, conduct, substance use and bipolar disorders; all p < 0.001) and impairments than controls. Disagreement between self- and collateral reports on childhood attention-deficit/hyperactivity disorder symptoms occurred in 38% of patients. Overall, attention-deficit/hyperactivity disorder disagreement and agreement groups had similar profiles in response to treatment and comorbidity, and the few differences detected in impairment measures were of small magnitude (Eta(2) < 0.05). CONCLUSION: Although collateral report has an important role for diagnosing attention-deficit/hyperactivity disorder in children, it has no incremental value in the evaluation of childhood attention-deficit/hyperactivity disorder symptoms in adults with a self-reported history of attention-deficit/hyperactivity disorder assessed in clinical settings.

Cadherin-13 gene is associated with hyperactive/impulsive symptoms in attention/deficit hyperactivity disorder.

Several efforts have been made to find new genetic risk variants which explain the high heritability of ADHD. At the genome level, genes involved in neurodevelopmental pathways were pointed as candidates. CDH13 and CTNNA2 genes are within GWAS top hits in ADHD and there are emerging notions about their contribution to ADHD pathophysiology. The main goal of this study is to test the association between SNPs in CDH13 and CTNNA2 genes and ADHD across the life cycle in subjects with ADHD. This study included 1,136 unrelated ADHD cases and 946 individuals without ADHD. No significant association between CDH13 and CTNNA2 was observed between cases and controls across different samples (P ≥ 0.096 for all comparisons). No allele was significantly more transmitted than expected from parents to ADHD probands. The CDH13 rs11150556 CC genotype was associated with more hyperactive/impulsive symptoms in youths with ADHD (children/adolescents clinical sample: F = 7.666, P = 0.006, FDR P-value = 0.032; Pelotas Birth Cohort sample: F = 6.711, P = 0.011, FDR P-value = 0.032). Although there are many open questions regarding the role of neurodevelopmental genes in ADHD symptoms, the present study suggests that CDH13 is associated with hyperactive/impulsive symptoms in youths with ADHD.

Association between telomere length with alcohol use disorder and internalizing/externalizing comorbidities in a Brazilian male sample.

BACKGROUND: Shortening telomere length (TL) is an important ageing marker associated with substance use disorder (SUD). However, the influence of psychiatric and clinical comorbidities and alcohol-related outcomes has not been much explored in the context of TL in individuals with alcohol use disorder (AUD) and may be a source of heterogeneity in AUD studies. Therefore, our aim was to investigate the influence of AUD, alcohol-related outcomes, and common psychiatric comorbidities on TL in men with AUD and healthy controls (HC). METHODS: Men with AUD (n = 108, mean age = 52.4, SD = 8.6) were recruited in a detoxification unit, and HC (n = 80, mean age = 50.04, SD = 9.1) from the blood bank, both located in Brazil. HC had no current or lifetime diagnosis of any substance use disorder. Psychiatric comorbidities were assessed using SCID-I. TL ratio was measured in triplicates using quantitative multiplex PCR. RESULTS: Telomere length did not differ between individuals with AUD and HC (p = 0.073) or was associated with AUD-related outcomes, trauma, or clinical comorbidities. Individuals with externalizing disorders had longer TL when comparing with those with internalizing disorders (p = 0.018) or without comorbidity (p = 0.018). CONCLUSION: Our findings indicate that TL was influenced by the presence of psychiatric comorbidity rather than case or control status. These results were adjusted for potential confounders, such as age.

Exploring Neuroimaging Association Scores in adulthood ADHD and middle-age trajectories.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder associated with brain differences in children, but not in adults. A combined evaluation of the regional brain differences could improve statistical power and, consequently, allow the detection of possible effects in adults. Thus, our aim is to verify whether Neuroimaging Association Scores (NAS) are associated with adulthood ADHD and clinical trajectories of the disorder in midlife. Clinical and neuroimaging data were collected for 121 subjects with ADHD (mean age: 47.1 ± 10.5; 43% male) and 82 controls (mean age: 38.2 ± 9.0; 54.9% male). Cases were assessed seven and thirteen years after baseline diagnosis, and their clinical trajectories were classified as stable if they fulfilled ADHD diagnosis in all assessments or unstable if they presented remission and recurrence of symptoms. Neuroimaging data were acquired in the last clinical assessment (thirteen years after baseline) and NAS were calculated as a weighted sum of the associations previously reported by meta-analyses for three types of structural brain modalities: cortical thickness, cortical surface area, and subcortical volume. The NAS for cortical surface area was higher in cases compared to controls. No association was found for NAS and number of symptoms of ADHD or clinical trajectories. The fact that differences were restricted to ADHD diagnostic status suggests a susceptibility effect that is not extended to subtle aspects of the disorder. Our results also suggest that evaluating overall effects may have advantages especially when applied to adult ADHD samples.

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

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.

An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder.

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prevalent psychiatric condition characterized by developmentally inappropriate symptoms of inattention and/or hyperactivity/impulsivity, which leads to impairments in the social, academic, and professional contexts. ADHD diagnosis relies solely on clinical assessment based on symptom evaluation and is sometimes challenging due to the substantial heterogeneity of the disorder in terms of clinical and pathophysiological aspects. Despite the difficulties imposed by the high complexity of ADHD etiology, the growing body of research and technological advances provide good perspectives for understanding the neurobiology of the disorder. Such knowledge is essential to refining diagnosis and identifying new therapeutic options to optimize treatment outcomes and associated impairments, leading to improvements in all domains of patient care. This review is intended to be an updated outline that addresses the etiological and neurobiological aspects of ADHD and its treatment, considering the impact of the "omics" era on disentangling the multifactorial architecture of ADHD.

Linking dopamine neurotransmission and neurogenesis: The evolutionary history of the NTAD (NCAM1-TTC12-ANKK1-DRD2) gene cluster.

Genetic studies have long suggested the important role of the DRD2 gene in psychiatric disorders and behavior. Further research has shown a conjoined effect of genes in the Chr11q22-23 region, which includes the NCAM1, TTC12, ANKK1 and DRD2 genes, or NTAD cluster. Despite a growing need to unravel the role of this cluster, few studies have taken into account interspecies and evolutionary approaches. This study shows that behaviorally relevant SNPs from the NTAD cluster, such as rs1800497 (Taq1A) and rs6277, are ancient polymorphisms that date back to the common ancestor between modern humans and Neanderthals/Denisovans. Conserved synteny and neighborhood indicate the NTAD cluster seems to have been established at least 400 million years ago, when the first Sarcopterygians emerged. The NTAD genes are apparently co-regulated and this could be attributed to adaptive functional properties, including those that emerged when the central nervous system became more complex. Finally, our findings indicate that NTAD genes, which are related to neurogenesis and dopaminergic neurotransmission, should be approached as a unit in behavioral and psychiatric genetic studies.

Association between Polygenic Risk Scores for ADHD and Asthma: A Birth Cohort Investigation.

OBJECTIVE: Shared genetic mechanisms have been hypothesized to explain the comorbidity between ADHD and asthma. To evaluate their genetic overlap, we relied on data from the 1982 Pelotas birth cohort to test the association between polygenic risk scores (PRSs) for ADHD (ADHD-PRSs) and asthma, and PRSs for asthma (asthma-PRSs) and ADHD. METHOD: We analyzed data collected at birth, 2, 22, and 30 years from 3,574 individuals. RESULTS: Subjects with ADHD had increased risk of having asthma (OR 1.92, 95% CI 1.01-3.66). The association was stronger for females. Our results showed no evidence of association between ADHD-PRSs and asthma or asthma-PRSs and ADHD. However, an exploratory analysis suggested that adult ADHD might be genetically associated with asthma. CONCLUSION: Our results do not support a shared genetic background between both conditions. Findings should be viewed in light of important limitations, particularly the sample size and the self-reported asthma diagnosis. Studies in larger datasets are required to better explore the genetic overlap between adult ADHD and asthma.