Attention Deficit Hyperactivity Disorder Traits Research Articles

Unpacking the overlap between Autism and ADHD in adults: A multi-method approach

The overlap between Autism and Attention-Deficit Hyperactivity Disorder (ADHD) is widely observed in clinical settings, with growing interest in their co-occurrence in neurodiversity research. Until relatively recently, however, concurrent diagnoses of Autism and ADHD were not possible. This has limited the scope for large-scale research on their cross-condition associations, further stymied by a dearth of open science practices in the neurodiversity field. Additionally, almost all previous research linking Autism and ADHD has focused on children and adolescents, despite them being lifelong conditions. Tackling these limitations in previous research, 5504 adults – including a nationally representative sample of the UK (Study 1; n = 504) and a large pre-registered study (Study 2; n = 5000) – completed well-established self-report measures of Autism and ADHD traits. A series of network analyses unpacked the associations between Autism and ADHD at the individual trait level. Low inter-item connectivity was consistently found between conditions, supporting the distinction between Autism and ADHD as separable constructs. Subjective social enjoyment and hyperactivity-impulsivity traits were most condition-specific to Autism and ADHD, respectively. Traits related to attention control showed the greatest Bridge Expected Influence across conditions, revealing a potential transdiagnostic process underlying the overlap between Autism and ADHD. To investigate this further at the cognitive level, participants completed a large, well-powered, and pre-registered study measuring the relative contributions of Autism and ADHD traits to attention control (Study 3; n = 500). We detected age- and sex-related effects, however, attention control did not account for the covariance between Autism and ADHD traits. We situate our findings and discuss future directions in the cognitive science of Autism, ADHD, and neurodiversity, noting how our open datasets may be used in future research.

Is Attention-Deficit/Hyperactivity Disorder (ADHD) a Dimension or a Category? What Does the Relationship Between ADHD Traits and Psychosocial Quality of Life Tell Us?

Objective: The question of whether attention-deficit/hyperactivity disorder (ADHD) is a discrete category or a continuous dimension remains clinically relevant. We report the first examination of this question from the viewpoint of the relationship between ADHD traits and psychosocial quality of life (QoL), and whether the level of QoL declines markedly around a certain high ADHD trait range suggestive of a categorical boundary. Methods: Parents/caregivers of 1,967 schoolchildren aged 6 to 11 from the general population completed the Pediatric Quality of Life Inventory and the ADHD-Rating Scale IV. Piecewise linear and non-linear regression analyses were performed. Results: No evidence for a non-linear association or an abrupt change in the rate of decrease in QoL was observed in the high end of the ADHD traits continuum. Instead, the relationship was consistent with linearity. Conclusion: Psychosocial QoL gradually declines in a linear manner as ADHD trait levels increase providing further support for a dimensional model.

Proactive inhibitory control as a cognitive contributor to social difficulties in adolescents with ADHD traits

Adolescents with attention deficit hyperactivity disorder (ADHD) represent a significantly heterogenous group in terms of cognitive and social ability. Given the high co-occurrence of ADHD and autism, it is unclear whether the social difficulties seen in ADHD may be attributed to the same underlying factors which contribute to social difficulties in autism, or are a unique feature of ADHD. This study explores differences in cognition in adolescents with clinically elevated ADHD symptoms with and without social difficulties, and adolescents with ADHD symptoms and autism. Thirty-nine adolescents completed objective measures of cognition (attention, working memory, inhibition) and social cognition (affect recognition, theory of mind [ToM]). Adolescents with ADHD symptoms and social difficulties had poorer proactive inhibition than both those without social difficulties, and those with autism. Lower cognitive performance was only significantly related to social functioning for adolescents with ADHD who experienced social difficulties. ToM was weakest in those with autism. Social difficulties in adolescents with clinically elevated ADHD symptoms are associated with poor proactive inhibition, working memory and affect recognition. This highlights the potential benefit of cognitive strategies for remediating social difficulties in ADHD, and the need for ADHD specific interventions. Lay abstract Around half of teenagers with attention deficit hyperactivity disorder (ADHD) experience significant difficulties forming and maintaining friendships. This in turn often has negative effects on schooling and mental health. There is a large body of research that suggests the social difficulties commonly seen in ADHD may be due to weaknesses in skills such as impulse control, working memory, recognising emotions, and perspective taking. Given teenagers with autism often present with similar weaknesses and social difficulties, it is not known whether the social difficulties experienced by teenagers with ADHD have the same underlying causes. If so, this may suggest that social difficulties in ADHD represent undiagnosed autism, or low-level autism traits. This study compared these key skills in teenagers with clinical ADHD symptoms who experience social difficulties, with those who don’t experience social difficulties, and those with co-occurring autism. The results showed that social difficulties in ADHD and autism appear to have different underlying causes, suggesting that the social difficulties seen in teenagers with ADHD are unique to this disorder, and are not due to underlying autism, or autism traits. This highlights the need for social skills interventions, particularly those that target impulse control, emotion recognition and working memory, that are specifically tailored to the needs and weaknesses of teenagers with ADHD, rather than using existing interventions designed for teenagers with autism.

An investigation on the alterations in Wnt signaling in ADHD across developmental stages

The canonical Wnt signaling pathway plays a vital role in the developmental processes of the Central Nervous System throughout both prenatal and postnatal stages, as well as in maintaining homeostasis during adulthood. Its complex intracellular cascade involves the participation of key proteins (i.e., GSK3β and β-catenin) to activate the transcription of Wnt target genes. These genes subsequently control processes like cell proliferation, maturation, and the determination of cell fate. Previous studies suggest that this pathway can also be associated with Attention-Deficit Hyperactivity Disorder (ADHD), a neurodevelopmental disorder with multifactorial etiology. This study aimed to clarify if and at what developmental stage the Wnt pathway is altered in ADHD. Accordingly, we carried out proteomic and functional assessments of the Wnt pathway using Western Blot and reporter assays, respectively. These assessments were performed at the induced pluripotent stem cell (iPSC), neural stem cell (NSC), and neuronal phases. IPSCs were generated from somatic cells retrieved from 5 controls and 5 patients diagnosed with ADHD. As opposed to the developmental stage of iPSCs, ADHD NSCs showed alterations in the protein expression of both GSK3β and β-catenin, suggesting increased Wnt activity in the ADHD group. Moreover, Wnt reporter assays confirmed higher Wnt activity in ADHD NSCs. Our molecular findings in NSCs correlated with genetic predisposition to ADHD and clinical traits displayed by their respective donors. In conclusion, these results suggest that a crucial cellular pathway is disrupted in patient-specific NSCs, potentially explaining the developmental deficits clinically exhibited by ADHD patients.

Adult attention-deficit/hyperactivity disorder traits in healthy adults associated with brain volumetric data identify precuneus involvement in traffic crashes

This large-scale study including 2548 healthy adults with no clinical attention-deficit/hyperactivity disorder (ADHD) diagnosis intended to clarify the complex relationships between cerebral grey matter volumes (GMVs), ADHD traits, and driving safety behaviours. Path analysis of magnetic resonance imaging (MRI) results and questionnaires about ADHD traits and traffic crashes over the past decade revealed significant correlations of ADHD traits with different brain regions relevant to different cognitive functions. The left precuneus responsible for visuospatial cognition was the sole region correlated with all ADHD trait categories, suggesting it plays an important role in understanding driving safety and traffic crashes. For the first time, a strong relationship was found among regional GMVs, ADHD traits, and real-life traffic crashes. These insights into the complex interplay may inform the development of an effective intervention with MRI examination to prevent traffic crashes. Large-scale brain volumetric data may further open social applications of behaviour science and neuroimaging.

Genome-Wide Analyses of Vocabulary Size in Infancy and Toddlerhood: Associations With Attention-Deficit/Hyperactivity Disorder, Literacy, and Cognition-Related Traits

BackgroundThe number of words children produce (expressive vocabulary) and understand (receptive vocabulary) changes rapidly during early development, partially due to genetic factors. Here, we performed a meta–genome-wide association study of vocabulary acquisition and investigated polygenic overlap with literacy, cognition, developmental phenotypes, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). MethodsWe studied 37,913 parent-reported vocabulary size measures (English, Dutch, Danish) for 17,298 children of European descent. Meta-analyses were performed for early-phase expressive (infancy, 15–18 months), late-phase expressive (toddlerhood, 24–38 months), and late-phase receptive (toddlerhood, 24–38 months) vocabulary. Subsequently, we estimated single nucleotide polymorphism–based heritability (SNP-h2) and genetic correlations (rg) and modeled underlying factor structures with multivariate models. ResultsEarly-life vocabulary size was modestly heritable (SNP-h2 = 0.08–0.24). Genetic overlap between infant expressive and toddler receptive vocabulary was negligible (rg = 0.07), although each measure was moderately related to toddler expressive vocabulary (rg = 0.69 and rg = 0.67, respectively), suggesting a multifactorial genetic architecture. Both infant and toddler expressive vocabulary were genetically linked to literacy (e.g., spelling: rg = 0.58 and rg = 0.79, respectively), underlining genetic similarity. However, a genetic association of early-life vocabulary with educational attainment and intelligence emerged only during toddlerhood (e.g., receptive vocabulary and intelligence: rg = 0.36). Increased ADHD risk was genetically associated with larger infant expressive vocabulary (rg = 0.23). Multivariate genetic models in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort confirmed this finding for ADHD symptoms (e.g., at age 13; rg = 0.54) but showed that the association effect reversed for toddler receptive vocabulary (rg = −0.74), highlighting developmental heterogeneity. ConclusionsThe genetic architecture of early-life vocabulary changes during development, shaping polygenic association patterns with later-life ADHD, literacy, and cognition-related traits.

Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability.

SYNGAP1-related ID is a genetic condition characterised by global developmental delay and epilepsy. Individuals with SYNGAP1-related ID also commonly show differences in attention and social communication/interaction and frequently receive additional diagnoses of Autism Spectrum Disorder (ASD) or Attention Deficit Hyperactivity Disorder (ADHD). We thus set out to quantify ASD and ADHD symptoms in children with this syndrome. To assess ASD and ADHD, parents and caregivers of a child with SYNGAP1-related ID (N = 34) or a typically developing control (N = 21) completed the Social Responsiveness Scale-2, the Social Communication Questionnaire with a subset of these also completing the Conners-3. We found that those with SYNGAP1-related ID demonstrated higher levels of autistic traits on both the SRS and SCQ than typically developing controls. On the SRS, those with SYNGAP1-related ID scored highest for restricted repetitive behaviours, and were least impaired in social awareness. On the Conners-3, those with SYNGAP1-related ID also showed a high prevalence of ADHD traits, with scores demonstrating difficulties with peer relations but relatively low occurrence of symptoms for DSM-5 conduct disorder and DSM-5 oppositional defiant disorder. Hierarchical clustering analysis highlighted distinct SYNGAP1-related ID subgroups for both ASD and ADHD traits. These findings provide further characterisation of the SYNGAP1-related ID behavioural phenotype, guiding diagnosis, assessment and potential interventions.

Glutamate receptor genetic variants affected peripheral glutamatergic transmission and treatment induced improvement of Indian ADHD probands

Attention deficit hyperactivity disorder (ADHD), a childhood-onset neurobehavioral disorder, often perturbs scholastic achievement and peer-relationship. The pivotal role of glutamate (Glu) in learning and memory indicated an influence of Glu in ADHD, leading to the exploration of Glu in different brain regions of ADHD subjects. We for the first time analyzed GluR genetic variations, Glu levels, as well as expression of Glu receptors (GluR) in the peripheral blood of eastern Indian ADHD probands to find out the relevance of Glu in ADHD prognosis. After obtaining informed written consent for participation, peripheral blood was collected for analyzing the genetic variants, Glu level, and expression of target genes. Since ADHD probands are often treated with methylphenidate or atomoxetine for providing symptomatic remediation, we have also tested post-therapeutic improvement in the ADHD trait scores in the presence of different GluR genotypes. Two variants, GRM7 rs3749380 “T” and GRIA1 rs2195450 “C”, exhibited associations with ADHD (P ≤ 0.05). A few GluR genetic variants showed significant association with higher trait severity, low IQ, lower plasma Glu level, down-regulated GluR mRNA expression, and poor response to medications. This indicates that down-regulated glutamatergic system may have an effect on ADHD etiology and treatment efficacy warranting further in-depth investigation.

Differences between subclinical attention-deficit/hyperactivity and autistic traits in default mode, salience, and frontoparietal network connectivities in young adult Japanese

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with attentional impairments, with both commonalities and differences in the nature of their attention deficits. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of attention-related large-scale brain networks (LSBNs). The participants were 61 healthy individuals (30 men; age, 21.9 ± 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and auditory oddball task (Odd). Considering the critical role in attention processing, we focused our analyses on the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Region of interest (ROI)-to-ROI analyses (false discovery rate < 0.05) were performed to determine relationships between psychological measures with within-network FC (DMN, FPN, and SN) as well as with between-network FC (DMN-FPN, DMN-SN, and FPN-SN). ASRS scores, but not AQ scores, were correlated with less frequent commission errors and shorter reaction times in the CPT. During Odd, significant positive correlations with ASRS were demonstrated in multiple FCs within DMN, while significant positive correlations with AQ were demonstrated in multiple FCs within FPN. AQs were negatively correlated with FPN-SN FCs. During Rest, AQs were negatively and positively correlated with one FC within the SN and multiple FCs between the DMN and SN, respectively. These findings of the ROI-to-ROI analysis were only partially replicated in a split-half replication analysis, a replication analysis with open-access data sets, and a replication analysis with a structure-based atlas. The better CPT performance by individuals with subclinical ADHD traits suggests positive effects of these traits on sustained attention. Differential associations between LSBN FCs and ASD/ADHD traits corroborate the notion of differences in sustained and selective attention between clinical ADHD and ASD.

Cortical responses to social stimuli in infants at elevated likelihood of ASD and/or ADHD: A prospective cross-condition fNIRS study

Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.

Prevalence of suspected autism spectrum disorder and attention-deficit hyperactivity disorder in a Japanese clinical sample with gambling disorder: A cross-sectional study.

Studies show gambling disorders are associated with attention-deficit hyperactivity disorder (ADHD). The association between gambling disorders and autism spectrum disorder (ASD) has not been well studied, although ASD is often comorbid with ADHD and is associated with gaming disorder. The aim of this study was to estimate the prevalence of ASD and ADHD traits comorbid with gambling disorders and to examine the relationships between these traits and gambling problems in a clinical population. This single-site cross-sectional study was conducted at a Japanese addiction outpatient clinic treating gambling disorders. The Autism-Spectrum Quotient (AQ) test and the Adult ADHD Self-Report Scale (ASRS) were used to screen ASD and ADHD. The Problem Gambling Severity Index (PGSI) was used to assess the severity of the gambling problems. We calculated the prevalence of suspected ASD and ADHD with 95% confidence intervals (CI) based on a binomial distribution and performed univariate analyses to examine the relationships between the AQ and ASRS scores and the total PGSI score. We included 97 of 197 potential participants. After screening the participants using the AQ and ASRS, we found that the prevalence of ASD traits was 29.8% (95% CI: 21.0%-40.2%), while the prevalence of ADHD traits was 26.0% (95% CI: 17.9%-36.2%). Univariate regression analyses revealed that the total AQ score was inversely associated with the total PGSI score. However, the total ASRS score and some ASRS subscores were positively associated with the total PGSI score. ASD and ADHD may be prevalent among patients with gambling disorders in clinical settings.

Three year outcomes in infants with a family history of autism and/or attention deficit hyperactivity disorder.

Most research on early outcomes in infants with a family history (FH) of autism has focussed on categorically defined autism, although some have language and developmental delays. Less is known about outcomes in infants with a FH of attention deficit hyperactivity disorder (ADHD). Infants with and without a FH of autism and/or ADHD, due to a first-degree relative with either or both conditions, were recruited at 5 or 10months. Three year outcomes were characterised using latent profile analysis (LPA) across measures of cognitive ability, adaptive functioning and autism, ADHD and anxiety traits (n=131). We additionally ran an LPA using only autism and ADHD measures, and the broader LPA in an independent cohort (n=139) and in both cohorts combined (n=270). A Low Developmental Level+High Behavioural Concerns class had elevated autism, ADHD and anxiety scores, low cognitive and adaptive function, and included all but one child with autism. A Low Developmental Level+Typical Behaviour class had average cognitive ability and typical behaviour but low adaptive function. A Typical Developmental Level+Some Behavioural Concerns class had average cognitive and adaptive function but slightly elevated behaviour scores. A High Developmental Level+Typical Behaviour class had above average cognitive ability and typical behaviour. All four LPAs identified classes characterised by combinations of either, or both, Low Development Level and elevated behaviour scores, as well as a typically developing class. No classes had elevated autism or ADHD traits in isolation. Some infants with a FH of autism or ADHD have atypical developmental and behavioural outcomes, but do not show strong autism or ADHD traits in isolation. The field needs to recalibrate aims and methods to embrace the broader transdiagnostic pattern of outcomes seen in these infants.

Mechanisms of cognitive disinhibition explain individual differences in adult attention deficit hyperactivity disorder traits

BackgroundAttention deficit hyperactivity disorder (ADHD) in adults is strongly associated with psychiatric comorbidity and functional impairment. Here, we aimed to use a newly developed online cognitive battery with strong psychometric properties for measuring individual differences in three cognitive mechanisms proposed to underlie ADHD traits in adults: 1) attentional control – the ability to mobilize cognitive resources to stop a prepotent motor response; 2) information sampling/gathering – adequate sampling of information in a stimulus detection task prior to making a decision; and 3) shifting - the ability to adapt behavior in response to positive and negative contingencies. MethodsThis cross-sectional and correlational study recruited 650 adults (330 males) aged 18–69 years (M = 33.06; MD = 31.00; SD = 10.50), with previously diagnosed ADHD (n = 329) and those from the general community without a history of ADHD (n = 321). Self-report measures of ADHD traits (i.e., inattention/disorganization, impulsivity, hyperactivity) and the cognitive battery were completed online. ResultsLatent class analysis, exploratory structural equation modeling and factor mixture modeling revealed self-reported ADHD traits formed a unidimensional and approximately normally distributed phenotype. Bayesian structural equation modeling demonstrated that all three mechanisms measured by the cognitive battery, explained unique, incremental variance in ADHD traits, with a total of 15.9% explained in the ADHD trait factor. ConclusionsAttentional control and shifting, as well as the less researched cognitive process of information gathering, explain individual difference variance in self-reported ADHD traits with potential to yield genetic and neurobiological insights into adult ADHD.

A prospective investigation of impacts of comorbid attention deficit hyperactivity disorder (ADHD) on clinical features and long-term treatment response in adult patients with obsessive-compulsive disorder (OCD)

BackgroundA close association between obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in children and adolescents has been investigated in previous studies. However, few studies examined the relationship between lifetime comorbidity of ADHD and OCD in adults. Therefore, we sought to investigate the clinical and psychopathological features related to comorbid ADHD in Japanese adult patients with OCD. MethodsWe assessed lifetime comorbidity of ADHD in 93 adult Japanese patients with OCD. Additionally, we used the Japanese version of Conners' Adult ADHD Rating Scales to assess the characteristics and severity of ADHD in each participant. According to the results, we excluded OCD patients that did not have ADHD but who exhibited elevated levels of ADHD traits. We compared OCD patients with ADHD (ADHD+ group) and those without ADHD or its trait (ADHD− group) in terms of background profiles and clinical features, such as OCD symptomatology and psychometric test results. Additionally, the 6-month treatment outcome was compared prospectively between groups. ResultsOf the 93 OCD participants, the prevalence of lifetime comorbidity of ADHD was estimated as 16.1%. Compared with the ADHD− group, participants in the ADHD+ group had an earlier age of onset of OCD, higher frequencies of hoarding symptoms, higher levels of depressive and anxiety symptoms and lower quality of life, more elevated levels of impulsivity, and higher rates of substance or behavioral addiction and major depression. Finally, the mean improvement rate on the Yale-Brown Obsessive Compulsive Scale after 6 months of standardized OCD treatment in the ADHD+ group (16.1%) was significantly lower than that in the ADHD− group (44.6%). ConclusionThe lifetime comorbidity of ADHD is likely to exert a significant effect on clinical features and treatment outcome in adult patients with OCD. It is important to consider that underlying ADHD pathology may function as a facilitator for increased severity of global clinical features and treatment refractory conditions in OCD patients. Further studies are required to examine treatment strategies for such patients.

A twin study of genetic and environmental contributions to attention-deficit/hyperactivity disorder over time.

Attention-deficit/hyperactivity disorder (ADHD) is an increasingly commonly diagnosed neurodevelopmental condition. One possibility is that this reflects a genuine increase in the prevalence of ADHD due to secular environmental changes, yet this hypothesis remains untested. We therefore investigated whether the genetic and environmental variance underlying ADHD, and traits of ADHD, has changed over time. We identified twins born from 1982 to 2008 from the Swedish Twin Registry (STR). We linked the STR with the Swedish National Patient Register and Prescribed Drug Register to identify diagnoses of ADHD and prescriptions of ADHD medication for these twins. We also utilized data collected from participants in the Child and Adolescent Twin Study in Sweden (CATSS), born from 1992 to 2008. Their parents completed a structured ADHD screening tool, which was used to measure traits of ADHD and assign broad screening diagnoses of ADHD. We used the classical twin design to test whether the degree to which variation in these measures was influenced by genetic and environmental variation changed over time. We included 22,678 twin pairs from the STR and 15,036 pairs from CATSS. The heritability of ADHD in the STR ranged from 66% to 86% over time, although these fluctuations were not statistically significant. We observed a modest increase in variance in ADHD traits, from 0.98 to 1.09. This was driven by small increases in the underlying genetic and environmental variance, with heritability estimated as 64%-65%. No statistically significant changes in variance in screening diagnoses were observed. The relative contribution of genetic and environmental factors to ADHD has remained stable over time, despite its increasing prevalence. Thus, changes in the underlying etiology of ADHD over time are unlikely to explain the increase in ADHD diagnoses.

Evaluation of Birth Weight and Neurodevelopmental Conditions Among Monozygotic and Dizygotic Twins

Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition. To estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks. A co-twin design was applied to this case-control study conducted in Sweden. Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022. Birth weight. Categorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs. The study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized β [B], -5.51 [95% CI, -10.09 to -0.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, -17.35 [95% CI, -28.66 to -6.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, -0.25 [95% CI, -0.39 to -0.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins. The findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.

Co-development of attention deficit hyperactivity disorder and autistic trait trajectories from childhood to early adulthood.

Attention deficit hyperactivity disorder (ADHD) and autism, defined as traits or disorders, commonly co-occur. Developmental trajectories of ADHD and autistic traits both show heterogeneity in onset and course, but little is known about how symptom trajectories co-develop into adulthood. Using data from a population cohort, the Avon Longitudinal Study of Parents and Children, we examined correlations between ADHD and autistic traits across development, using the Social Communication Disorders Checklist and ADHD subscale of the Strengths and Difficulties Questionnaire. We modelled joint developmental trajectories of parent-reported ADHD and autistic traits between 4 and 25 years, then characterised trajectory classes based on sociodemographic, perinatal, psychopathology, cognition and social functioning variables and tested for associations with neurodevelopmental/psychiatric polygenic scores (PGS). Three classes of trajectories were identified; a typically developing majority with low-stable ADHD-autistic traits (87%), a male-predominant subgroup with child/adolescent-declining traits (6%) and a subgroup with late-emerging traits (6%). ADHD-autistic trait correlations were greatest in young adulthood for the two nontypically developing classes. There were higher rates of emotional and conduct problems, low IQ, childhood seizures and poor social functioning in the declining and late-emerging classes compared to the low-stable class. Emotional, conduct and peer problems were more prevalent during childhood in the childhood/adolescent-declining class compared to other classes, but were more prevalent in young adulthood in the late-emerging class. Neurodevelopmental/psychiatric PGS also differed: both nontypically developing classes showed elevated ADHD PGS compared to the low-stable group, and the late-emerging group additionally showed elevated schizophrenia PGS and decreased executive function PGS, whereas the declining group showed elevated broad depression PGS. Distinct patterns of ADHD-autism co-development are present across development in the general population, each with different characterising factors and genetic signatures as indexed by PGS.

0227 Impact of 5-night sleep restriction on actigraphy-estimated sleep in young adolescents: preliminary associations with ADHD traits

Abstract Introduction Prior research suggests that children with attention-deficit/hyperactivity-disorder (ADHD) may experience disrupted sleep. In typically developing children, short-term sleep restriction increases sleep pressure and efficiency; however, whether a similar homeostatic response occurs in children with ADHD is unknown. Here we explore the effects of 5 nights of experimental sleep restriction on actigraphy-estimated sleep of children with and without high ADHD characteristics. Methods Nineteen young adolescents (Mage=12.24yr, range 10.17-13.88yr; 10F/9M) participated in an at-home crossover protocol. After ≥5 nights of stabilization (10hr time-in-bed[TIB] set to habitual risetimes), participants had five nights of sleep optimization (SO; same stabilization schedule) or restriction (SR; 7.5hr TIB, sleep opportunity reduced by delaying bedtime and advancing risetime equally), a 2-3 night restabilization, and then the reverse schedule. Sleep was assessed via wrist-worn actigraphy (AMI Micro Motionlogger), sleep diaries, and twice-daily phone calls ensuring schedule adherence. Primary sleep variables included: total sleep time (TST; min), sleep period time (SPT; min), and sleep efficiency (TST/SPT*100). Children were grouped by parent-rated Conners 3 ADHD-Probability-Index: &amp;lt; 50% (low-ADHD; n=10, 8F) or &amp;gt;=50% (high-ADHD; n=9, 2F). Results Mixed-effects ANOVAs evaluating condition (SO vs. SR) and group (low- vs. high-ADHD) on schedule adherence indicated significant effects of condition; that is, SR reduced both SPT (M±SD SO=9.08[0.54]hr, SR=7.10[0.57]hr; F(1,17)=479.75, p&amp;lt;.001, ηp2=.97) and TST (M±SD SO=7.92[0.97]hr, SR=6.38[0.86]hr; F(1,17)=302.13, p&amp;lt;.001, ηp2=.95). No group or group-by-condition effects were significant (all ps&amp;gt;.21). For sleep efficiency, a group-x-condition interaction (F(1,17)=8.29, p=.01, ηp2=.33) revealed that SR significantly increased sleep efficiency in low-ADHD children (M±SD SO=85.08[9.95]%, SR=89.74[7.66]%, Bonferroni-p&amp;lt;.001) but not in high-ADHD children (M±SD SO=90.67[3.74]%, SR=91.21[3.19]%, Bonferroni-p=.61). Other between-group effects were not significant (all ps&amp;gt;.12). Conclusion These preliminary data indicate that our sleep restriction protocol successfully reduces sleep opportunity and sleep duration in peripubertal children, including those with high ADHD traits. Notably, sleep restriction improved sleep efficiency in low-ADHD children, whereas sleep efficiency was high and unchanging in our high-ADHD group. It is possible that high-ADHD children maintained higher sleep pressure even after stabilization. While data collection (matching groups on sex and age) continues, we are examining waking EEG markers to explore this possibility. Support (if any) R01HD103655, P20GM139743

Association between marital satisfaction of female patients with persistent depressive disorder, and their own and husbands' autism spectrum disorder or attention deficit/hyperactivity disorder traits.

Patients' and spouses' neurodevelopmental traits may influence marital relationships, which are significantly associated with depressive symptoms. However, no studies have examined marital relationships in persistent depressive disorder (PDD) in terms of neurodevelopmental traits. This study aimed to explore the association between the autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) traits of female PDD patients and both partners' (patient and husband) marital satisfaction. A cross-sectional online survey was administered during two predetermined consecutive months at seven institutions. Participants were female outpatients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for PDD and their husbands. The instruments of the study were the following validated surveys: the Quality Marriage Index (QMI), the Autism-Spectrum Quotient Japanese version-21 (AQ-J-21), and the Adult ADHD Self-Report Scale Part A (ASRS Part A). The patients' AQ-J-21 showed a positive significant association with their QMI in all patients who responded to this study's questionnaire, whereas among couples wherein both patient and husband responded, the ASRS Part A exhibited a positive significant association with the patients' QMI. Conversely, the husbands' ASRS Part A exhibited a negative significant association with the patients' QMI. The patients' ASD and ADHD traits may play a positive role in the marital satisfaction of female PDD patients, while their husbands' ADHD traits may play a negative role. For female PDD patients with low marital satisfaction, it may be important to consider whether their husbands have ADHD traits; if so, it may be necessary to develop intervention strategies focused on the traits for improving the low marital satisfaction. However, our conclusions are not sufficiently convincing.

Maternal cortisol in 3rd trimester is associated with traits of neurodevelopmental disorder in offspring. Odense Child Cohort.

BackgroundPrenatal cortisol exposure is essential for neurodevelopment. Maternal cortisol levels could be associated with offspring autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). AimTo investigate associations between maternal 3rd trimester cortisol and offspring traits of ASD and ADHD. Material and methodsMother-child pairs were included from the prospective study Odense Child Cohort. Morning serum cortisol and 24-hour urine cortisol/cortisone were collected at gestational week 27–30. Offspring ASD and ADHD traits were assessed at age three and five years using the Child Behavior Checklist. Maternal cortisol measurements and offspring ASD and ADHD traits assessment were available in (n = 1131; 52% boys) mother-child pairs at age three and (n = 717; 54% boys) at five years of age. Maternal 24-hour urine measurement was available in a subset, at offspring three years of age (n = 300) and at five years of age (n = 217). Associations between maternal cortisol (continuous and tertiles) and offspring ASD or ADHD traits were examined in regression models adjusted for offspring sex, maternal age, pre-pregnancy BMI, parity, maternal education level, parental psychiatric disorders, and maternal smoking and stratified for offspring sex. ResultsMaternal mean age ( ± SD) was 30 years ( ± 4.4) and median BMI (25%; 75% percentiles) 23.5 kg/m2 (21.3; 26.6). Higher maternal serum cortisol levels were associated with higher prevalence of offspring ASD traits at three years of age in the total study cohort and in boys after stratifying for offspring sex. In the total population, tertiles of serum cortisol showed a significant dose-response relationship to ASD traits in unadjusted and adjusted models (p-values for linear trend, p < 0.01 and p = 0.02, respectively). In offspring at five years, associations between maternal cortisol and offspring ASD traits were non-significant (all p-values > 0.2). Maternal cortisol was not associated with offspring ADHD traits (all p-values > 0.07) in offspring at three and five years. Maternal 24-hour urine cortisol, cortisone, or cortisol/cortisone ratio were not associated with offspring ASD or ADHD traits. ConclusionHigher maternal serum cortisol in 3rd trimester was associated with offspring ASD traits at three years of age in the whole study cohort and in boys, but not in girls. This association was non-significant at five years of age.