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People with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) have abnormalities in frontal, temporal, parietal and striato-thalamic networks. It is unclear to what extent these abnormalities are distinctive or shared. This comparative meta-analysis aimed to identify the most consistent disorder-differentiating and shared structural and functional abnormalities.
Systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies of cognitive control comparing people with ASD or ADHD with typically developing controls. Regional gray matter volume (GMV) and fMRI abnormalities during cognitive control were compared in the overall sample and in age-, sex- and IQ-matched subgroups with seed-based d mapping meta-analytic methods.
Eighty-six independent VBM (1533 ADHD and 1295 controls; 1445 ASD and 1477 controls) and 60 fMRI datasets (1001 ADHD and 1004 controls; 335 ASD and 353 controls) were identified. The VBM meta-analyses revealed ADHD-differentiating decreased ventromedial orbitofrontal (z = 2.22, p < 0.0001) but ASD-differentiating increased bilateral temporal and right dorsolateral prefrontal GMV (zs ⩾ 1.64, ps ⩽ 0.002). The fMRI meta-analyses of cognitive control revealed ASD-differentiating medial prefrontal underactivation but overactivation in bilateral ventrolateral prefrontal cortices and precuneus (zs ⩾ 1.04, ps ⩽ 0.003). During motor response inhibition specifically, ADHD relative to ASD showed right inferior fronto-striatal underactivation (zs ⩾ 1.14, ps ⩽ 0.003) but shared right anterior insula underactivation.
People with ADHD and ASD have mostly distinct structural abnormalities, with enlarged fronto-temporal GMV in ASD and reduced orbitofrontal GMV in ADHD; and mostly distinct functional abnormalities, which were more pronounced in ASD.
Attention-deficit/hyperactivity disorder (ADHD) is associated with disrupted emotional processes including impaired regulation of approach behavior and positive affect, irritability, and anger. Enhanced reactivity to emotional cues may be an underlying process. Pupil dilation is an indirect index of arousal, modulated by the autonomic nervous system and activity in the locus coeruleus-noradrenergic system. In the current study, pupil dilation was recorded while 8- to 12- year old children (n = 71, 26 with a diagnosis of ADHD and 45 typically developing), viewed images of emotional faces. Parent-rated hyperactive/impulsive symptoms were uniquely linked to higher pupil dilation to happy, but not fearful, angry, or neutral faces. This was not explained by comorbid externalizing symptoms. Together, these results suggest that hyperactive/impulsive symptoms are associated with hyperresponsiveness to approach-related emotional cues across a wide range of symptom severity.
There is limited understanding of the cognitive profiles of Spanish-speaking children with Attention-Deficit/Hyperactivity Disorder (ADHD). The current study investigated the cognitive cluster profiles of Puerto Rican Spanish-speaking children with ADHD using the Wechsler Intelligence Scales for Children-Fourth Edition Spanish (WISC-IV Spanish) Index scores and examined the association between cognitive cluster profiles with other potentially relevant factors.
Hierarchical cluster analysis was used to identify WISC-IV clusters in a sample of 165 Puerto Rican children who had a primary diagnosis of ADHD. To examine the validity of the ADHD clusters, analysis of variances and chi-square analyses were conducted to compare the clusters across sociodemographics (e.g., age and education), type of ADHD diagnosis (ADHD subtype, Learning Disorder comorbidity), and academic achievement.
Clusters were differentiated by level and pattern of performance. A five-cluster solution was identified as optimal that included (C1) multiple cognitive deficits, (C2) processing speed deficits, (C3) generally average performance, (C4) perceptual reasoning strengths, and (C5) working memory deficits. Among the five clusters, the profile with multiple cognitive deficits was characterized by poorer performance on the four WISC-IV Spanish Indexes and was associated with adverse sociodemographic characteristics.
Results illustrate that there is substantial heterogeneity in cognitive abilities of Puerto Rican Spanish-speaking children with ADHD, and this heterogeneity is associated with a number of relevant outcomes.
This study integrated an experimental medicine approach and a randomized cross-over clinical trial design following CONSORT recommendations to evaluate a cognitive training (CT) intervention for attention deficit hyperactivity disorder (ADHD). The experimental medicine approach was adopted because of documented pathophysiological heterogeneity within the diagnosis of ADHD. The cross-over design was adopted to provide the intervention for all participants and make maximum use of data.
Children (n = 93, mean age 7.3 +/− 1.1 years) with or sub-threshold for ADHD were randomly assigned to CT exercises over 15 weeks, before or after 15 weeks of treatment-as-usual (TAU). Fifteen dropped out of the CT/TAU group and 12 out of the TAU/CT group, leaving 66 for cross-over analysis. Seven in the CT/TAU group completed CT before dropping out making 73 available for experimental medicine analyses. Attention, response inhibition, and working memory were assessed before and after CT and TAU.
Children were more likely to improve with CT than TAU (27/66 v. 13/66, McNemar p = 0.02). Consistent with the experimental medicine hypotheses, responders improved on all tests of executive function (p = 0.009–0.01) while non-responders improved on none (p = 0.27–0.81). The degree of clinical improvement was predicted by baseline and change scores in focused attention and working memory (p = 0.008). The response rate was higher in inattentive and combined subtypes than hyperactive-impulsive subtype (p = 0.003).
Targeting cognitive dysfunction decreases clinical symptoms in proportion to improvement in cognition. Inattentive and combined subtypes were more likely to respond, consistent with targeted pathology and clinically relevant heterogeneity within ADHD.
Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterised by inattention and hyperactivity-impulsivity that can affect people throughout their life course. A social gradient exists in the prevalence of ADHD in the UK. Studies in other countries have shown that social gradients also exist in the receipt of medication for ADHD. Socioeconomic position is potentially an unrecognised and modifiable factor in children and young people's receipt of medication for ADHD in the UK.
The aim of the study was to investigate if socioeconomic position could explain in part whether or not children and young people in Sheffield are receiving medication for ADHD.
We used multivariate logistic regression modelling to investigate whether socioeconomic position could explain variation in receipt of medication for ADHD in children and young people in a cross-sectional study. We collected data from 1354 children and young people with a diagnosis of ADHD across three Sheffield centres between January and December 2016. Independent variables were age, gender, religion, ethnicity, comorbidities, and Index of Multiple Deprivation decile (derived from home postcode).
Our results showed a social gradient in the receipt of medication for ADHD (P<0.01); an increase in one decile of the Index of Multiple Deprivation was associated with 10% lower odds of receipt of medication for ADHD (adjusted odds ratio 0.90, 95% CI 0.84–0.97).
Children and young people from more deprived backgrounds are more likely to receive medication for ADHD. This is the first time that a social gradient in children and young people's receipt of medication for ADHD has been shown in a UK sample.
Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.
Healthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.
Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.
Single doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
Children with complex CHD are at risk for psychopathology such as severe attention-deficit/hyperactivity disorder symptoms after congenital heart surgery.
The aim of this study was to investigate if children with Ventricular Septal Defect, Transposition of Great Arteries, or Tetralogy of Fallot have an increased occurrence of attention-deficit/hyperactivity disorder symptoms compared with the background population and to investigate differences between the three CHDs in terms of occurrence and appearance of attention-deficit/hyperactivity disorder symptoms.
A national register-based survey was conducted, including children aged 10–16 years with surgically corrected CHDs without genetic abnormalities and syndromes. The Attention-Deficit/Hyperactivity Disorder-Rating Scale questionnaires were filled in by parents and school teachers.
In total, 159 out of 283 questionnaires were completed among children with CHDs and compared with age- and sex-matched controls. Children with CHDs had significantly increased inattention scores (p = 0.009) and total attention-deficit/hyperactivity disorder scores (p = 0.008) compared with controls. Post hoc analyses revealed that children with Tetralogy of Fallot had significantly higher inattention scores compared with children both with Ventricular Septal Defect (p = 0.043) and controls (p = 0.004).
Attention-deficit/hyperactivity disorder symptoms and inattention symptoms were significantly more frequent among children aged 10–16 years with CHDs, in particular in children with corrected Tetralogy of Fallot.
The dopamine transporter gene (DAT1), striatal network dysfunction, and visual memory deficits have been consistently reported to be associated with attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine the effects of the DAT1 rs27048 (C)/rs429699 (T) haplotype on striatal functional connectivity and visual memory performance in youths with ADHD.
After excluding those who had excessive head motion, a total of 96 drug-naïve youths with ADHD and 114 typically developing (TD) youths were assessed with the resting-state functional magnetic resonance imaging and the delayed matching to sample (DMS) task for visual memory. We examined the effects of ADHD, DAT1 CT haplotype, and the ADHD × CT haplotype interaction on the functional connectivity of five striatal seeds. We also correlated visual memory performance with the functional connectivity of striatal subregions, which showed significant diagnosis × genotype interactions.
Compared with TD youths, ADHD youths showed significant hypoconnectivity of the left dorsal caudate (DC) with bilateral sensorimotor clusters. Significant diagnosis × genotype interactions were found in the connectivity between the left DC and the right sensorimotor cluster, and between the right DC and the left dorsolateral prefrontal/bilateral anterior cingulate clusters. Furthermore, the connectivity of the left DC showing significant diagnosis × genotype interactions was associated with DMS performance in youths with ADHD who carried the DAT1 CT haplotype.
A novel gene-brain-behavior association between the left DC functional connectivity and visual memory performance in ADHD youths with the DAT1 rs27048 (C)/rs429699 (T) haplotype suggests a differential effect of DAT1 genotype altering specific brain function causing neuropsychological dysfunction in ADHD.
Adults with attention deficit hyperactivity disorder (ADHD) frequently suffer from sleep problems and report high levels of daytime sleepiness compared to neurotypical controls, which has detrimental effect on quality of life.
We evaluated daytime sleepiness in adults with ADHD compared to neurotypical controls using an observer-rated sleepiness protocol during the Sustained Attention Response Task as well as electroencephalogram (EEG) slowing, a quantitative electroencephalographic measure collected during a short period of wakeful rest.
We found that adults with ADHD were significantly sleepier than neurotypical controls during the cognitive task and that this on-task sleepiness contributed to cognitive performance deficits usually attributed to symptoms of ADHD. EEG slowing predicted severity of ADHD symptoms and diagnostic status, and was also related to daytime sleepiness. Frontal EEG slowing as well as increased frontal delta were especially prominent in adults with ADHD. We have validated and adapted an objective observer-rated measure for assessing on-task sleepiness that will contribute to future sleep research in psychology and psychiatry.
These findings indicate that the cognitive performance deficits routinely attributed to ADHD and often conceptualized as cognitive endophenotypes of ADHD are largely due to on-task sleepiness and not exclusively due to ADHD symptom severity. Daytime sleepiness plays a major role in cognitive functioning of adults with ADHD.
Attention-deficit/hyperactivity disorder (ADHD) is a developmental condition that often persists into adulthood with extensive negative consequences on quality of life. Despite emerging evidence indicating the genetic basis of ADHD, investigations into the familial expression of latent neurocognitive traits remain limited.
In a group of adult ADHD probands (n = 20), their unaffected first-degree relatives (n = 20) and typically developing control participants (n = 20), we assessed endophenotypic alterations in the default mode network (DMN) connectivity during resting-state functional magnetic resonance imaging in relation to cognitive performance and clinical symptoms. In an external validation step, we also examined the dimensional nature of this neurocognitive trait in a sample of unrelated healthy young adults (n = 100) from the Human Connectome Project (HCP).
The results illustrated reduced anti-correlations between the posterior cingulate cortex/precuneus and right middle frontal gyrus that was shared between adult ADHD probands and their first-degree relatives, but not with healthy controls. The observed connectivity alterations were linked to higher ADHD symptoms that was mediated by performance in a sustained attention task. Moreover, this brain-based neurocognitive trait dimensionally explained ADHD symptom variability in the HCP sample.
Alterations in the default mode connectivity may represent a dimensional endophenotype of ADHD, hence a significant aspect of the neuropathophysiology of this disorder. As such, brain network organisation can potentially be employed as an important neurocognitive trait to enhance statistical power of genetic studies in ADHD and as a surrogate efficacy endpoint in the development of novel pharmaceuticals.
ADHD is one of the most common neurobehavioral disorders among children and adolescents. In this prospective study, we aimed to measure circulating zinc and ferritin levels in children with ADHD, pick up the deficient ones to give zinc and iron supplements then compare before and after treatment according to their Conner’s scores and Wecsler IQ test. Current study included fifty children diagnosed as having ADHD by DSMV criteria, their zinc and ferritin levels were measured by Colorimetric method and enzyme-linked immunosorbent assay (ELISA) respectively. They were divided into: group I (zinc only deficient),group II (zinc and ferritin deficient),group III (non-deficient), cases with mineral deficiency received zinc (55 mg/day) and/or iron (6 mg/kg/day) for 6 months then reassessed by parent Conner’s rating scale. In group 1, there was no significant difference between the Wecsler verbal and non-verbal IQ scores and oppositional and cognitive problems in Conner’s scores before and after zinc supplements, although there was significant improvement in attention, hyperactivity, emotional liability and impulsivity. In group II, there was significant improvement in verbal and total IQ but not in performance IQ, also there was significant improvement in hyperactivity, emotional liability and impulsivity with no significant difference in oppositional, cognitive problems and inattention before and after zinc/ iron supplements. In Conclusion, Zinc supplements in adjuvant to the main treatment significantly improved symptoms of ADHD children. However, a combined zinc and iron supplements was superior to zinc alone in alleviating ADHD symptoms as well as IQ improvement.
Altered resting-state functional connectivity (rsFC) has been noted in large-scale functional networks in attention-deficit/hyperactivity disorder (ADHD). However, identifying consistent abnormalities of functional networks is difficult due to varied methods and results across studies. To integrate rsFC alterations and search for coherent patterns of intrinsic functional network impairments in ADHD, this research conducts a coordinate-based meta-analysis of voxel-wise seed-based rsFC studies comparing rsFC between ADHD patients and healthy controls. A total of 25 datasets from 21 studies including 700 ADHD patients and 580 controls were analyzed. We extracted the coordinates of seeds and between-group effects. Each seed was then categorized into a seed-network by its location within priori 7-network parcellations. Then, pooled meta-analyses were conducted for the default mode network (DMN), frontoparietal network (FPN) and affective network (AN) separately, but not for the ventral attention network (VAN), dorsal attention network (DAN), somatosensory network (SSN) and visual network due to a lack of primary studies. The results showed that ADHD was characterized by hyperconnectivity between the FPN and regions of the DMN and AN as well as hypoconnectivity between the FPN and regions of the VAN and SSN. These findings not only support the triple-network model of pathophysiology associated with ADHD but also extend this model by highlighting the involvement of the SSN and AN in the mechanisms of network interactions that may account for motor hyperactivity and impulsive symptoms.
Childhood disruptive behaviors are highly prevalent and associated with adverse long-term social and economic outcomes. Trajectories of welfare receipt in early adulthood and the association of childhood behaviors with high welfare receipt trajectories have not been examined.
Boys (n = 1000) from low socioeconomic backgrounds were assessed by kindergarten teachers for inattention, hyperactivity, aggression, opposition, and prosociality, and prospectively followed up for 30 years. We used group-base trajectory modeling to estimate trajectories of welfare receipt from age 19–36 years using government tax return records, then examined the association between teacher-rated behaviors and trajectory group membership using mixed effects multinomial regression models.
Three trajectories of welfare receipt were identified: low (70.8%), declining (19.9%), and chronic (9.3%). The mean annual personal employment earnings (US$) for the three groups at age 35/36 years was $36 500 (s.d. = $24 000), $15 600 (s.d. = $16 275), and $1700 (s.d. = $4800), respectively. Relative to the low welfare receipt group, a unit increase in inattention (mean = 2.64; s.d. = 2.32, range = 0–8) at age 6 was associated with an increased risk of being in the chronic group (relative risk ratio; RRR = 1.16, 95% CI 1.03–1.31) and in the declining group (RRR = 1.13, 95% CI 1.03–1.23), after adjustment for child IQ and family adversity, and independent of other behaviors. Family adversity was more strongly associated with trajectories of welfare receipt than any behavior.
Boys from disadvantaged backgrounds exhibiting high inattention in kindergarten are at elevated risk of chronic welfare receipt during adulthood. Screening and support for inattentive behaviors beginning in kindergarten could have long-term social and economic benefits for individuals and society.
This study used repeated measures data to identify developmental profiles of elevated risk for ADHD (i.e., six or more inattentive and/or hyperactive-impulsive symptoms), with an interest in the age at which ADHD risk first emerged. Risk factors that were measured across the first 3 years of life were used to predict profile membership. Participants included 1,173 children who were drawn from the Family Life Project, an ongoing longitudinal study of children's development in low-income, nonmetropolitan communities. Four heuristic profiles of ADHD risk were identified. Approximately two thirds of children never exhibited elevated risk for ADHD. The remaining children were characterized by early childhood onset and persistent risk (5%), early childhood limited risk (10%), and middle childhood onset risk (19%). Pregnancy and delivery complications and harsh-intrusive caregiving behaviors operated as general risk for all ADHD profiles. Parental history of ADHD was uniquely predictive of early onset and persistent ADHD risk, and low primary caregiver education was uniquely predictive of early childhood limited ADHD risk. Results are discussed with respect to how changes to the age of onset criterion for ADHD in DSM5 may affect etiological research and the need for developmental models of ADHD that inform ADHD symptom persistence and desistance.
This study examined whether the interaction between parenting and inhibitory control predicts hyperactivity-impulsivity and inattention in 195 children. Observation data of positive parenting were collected at 4 years, and mother reports of coercive parenting at 5 years, inhibitory control at 6 years, and hyperactivity-impulsivity/inattention at 7 years were obtained. The common and unique variance of hyperactivity-impulsivity and inattention symptoms were examined as outcomes using a bifactor model. Results indicated that positive parenting practices predicted lower levels of hyperactivity-impulsivity/inattention behaviors at age 7 only when children's inhibitory control was high. These results support the vantage sensitivity model, which posits that some individuals show an increased sensitivity to positive experiences exclusively, and support the appropriateness of a targeted prevention approach in early childhood.
Mounting evidence shows genetic overlap between multiple psychiatric disorders. However, the biological underpinnings of shared risk for psychiatric disorders are not yet fully uncovered. The identification of underlying biological mechanisms is crucial for the progress in the treatment of these disorders.
We applied gene-set analysis including 7372 gene sets, and 53 tissue-type specific gene-expression profiles to identify sets of genes that are involved in the etiology of multiple psychiatric disorders. We included genome-wide meta-association data of the five psychiatric disorders schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, and attention-deficit/hyperactivity disorder. The total dataset contained 159 219 cases and 262 481 controls.
We identified 19 gene sets that were significantly associated with the five psychiatric disorders combined, of which we excluded five sets because their associations were likely driven by schizophrenia only. Conditional analyses showed independent effects of several gene sets that in particular relate to the synapse. In addition, we found independent effects of gene expression levels in the cerebellum and frontal cortex.
We obtained novel evidence for shared biological mechanisms that act across psychiatric disorders and we showed that several gene sets that have been related to individual disorders play a role in a broader range of psychiatric disorders.
Persons diagnosed with attention-deficit hyperactivity disorder (ADHD) have been found to have an increased risk of suicidal behaviour, but the pathway remains to be thoroughly explored.
To determine whether persons with ADHD are more likely to present with suicidal behaviour (i.e. suicide attempts and deaths by suicide) if they have a comorbid psychiatric disorder.
Using nationwide registers covering the entire population of Denmark, this cohort study of 2.9 million individuals followed from 1 January 1995 until 31 December 2014, covers more than 46 million person-years. All persons aged ≥10 years with Danish-born parents were identified and persons with a diagnosis of ADHD were compared with persons without. Incidence rate ratios (IRRs) were calculated by Poisson regression, with adjustments for sociodemographics and parental suicidal behaviour.
Persons with ADHD were followed for 164 113 person-years and 697 suicidal outcomes were observed. This group was found to have an IRR of suicidal behaviour of 4.7 (95% CI, 4.3–5.1) compared with those without ADHD. Persons with ADHD only had a 4.1-fold higher rate (95% CI, 3.5–4.7) when compared with those without any psychiatric diagnoses. For persons with ADHD and comorbid disorders the IRR was higher yet (IRR: 10.4; 95% CI, 9.5–11.4).
This study underlines the link between ADHD and an elevated rate of suicidal behaviour, which is significantly elevated by comorbid psychiatric disorders. In sum, these results suggest that persons with ADHD and comorbid psychiatric disorders are targets for suicide preventive interventions.
Optimal transition from child to adult services involves continuity, joint care, planning meetings and information transfer; commissioners and service providers therefore need data on how many people require that service. Although attention-deficit hyperactivity disorder (ADHD) frequently persists into adulthood, evidence is limited on these transitions.
To estimate the national incidence of young people taking medication for ADHD that require and complete transition, and to describe the proportion that experienced optimal transition.
Surveillance over 12 months using the British Paediatric Surveillance Unit and Child and Adolescent Psychiatry Surveillance System, including baseline notification and follow-up questionnaires.
Questionnaire response was 79% at baseline and 82% at follow-up. For those aged 17–19, incident rate (range adjusted for non-response) of transition need was 202–511 per 100 000 people aged 17–19 per year, with successful transition of 38–96 per 100 000 people aged 17–19 per year. Eligible young people with ADHD were mostly male (77%) with a comorbid condition (62%). Half were referred to specialist adult ADHD and 25% to general adult mental health services; 64% had referral accepted but only 22% attended a first appointment. Only 6% met optimal transition criteria.
As inclusion criteria required participants to be on medication, these estimates represent the lower limit of the transition need. Two critical points were apparent: referral acceptance and first appointment attendance. The low rate of successful transition and limited guideline adherence indicates significant need for commissioners and service providers to improve service transition experiences.
Brain structural alterations are frequently observed in probands with attention-deficit/hyperactivity disorder (ADHD). Here we examined the microstructural integrity of 76 white matter tracts among unaffected siblings of patients with ADHD to evaluate the potential familial risk and its association with clinical and neuropsychological manifestations.
The comparison groups included medication-naïve ADHD probands (n = 50), their unaffected siblings (n = 50) and typically developing controls (n = 50, age-and-sex matched with ADHD probands). Whole brain tractography was reconstructed automatically by tract-based analysis of diffusion spectrum imaging (DSI). Microstructural properties of white matter tracts were represented by the values of generalized fractional anisotropy (GFA), fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD).
Compared to the control group, ADHD probands showed higher AD values in the perpendicular fasciculus, superior longitudinal fasciculus I, corticospinal tract, and corpus callosum. The AD values of unaffected siblings were in the intermediate position between those of the ADHD and control groups. These AD values were significantly associated with ADHD symptoms, sustained attention and working memory, for all white matter tracks evaluated except for the perpendicular fasciculus. Higher FA and lower RD values in the right frontostriatal tract connecting ventrolateral prefrontal cortex (FS-VLPFC) were associated with better performance in spatial span only in the unaffected sibling group.
Abnormal AD values of specific white matter tracts among unaffected siblings of ADHD probands suggest the presence of familial risk in this population. The right FS-VLPFC may have a role in preventing the expression of the ADHD-related behavioral phenotype.
Attention-deficit hyperactivity disorder and autism are increasingly recognised in adults. For a diagnostic evaluation, parental information on childhood development is needed. However, no instruments that retrospectively describe neurodevelopmental problems in childhood are validated for evaluating adults. The 181-item parent-report questionnaire Five to Fifteen (FTF) is nevertheless frequently used for assessments in adulthood.
To examine if FTF is reliable for obtaining retrospective neurodevelopmental history among young adults.
Details of parents who had assessed their children with the FTF for neuropsychiatric evaluation were retrieved and they were asked to complete the FTF again 10–19 years later. Agreements between original and retrospective scorings were analysed.
Long-term reliability for FTF varies considerably between individual items. Several difficulties are reported as more severe at the retrospective scoring than at the original scoring. A selection of 24 items (FTF-Brief) with good agreement over time, is presented for use in adult psychiatry settings.
Neuropsychiatric symptoms may fluctuate over time and become more prominent when demands increase. Informants' recollections of their child's neurodevelopmental symptoms may be a selection of symptoms that are longstanding rather than present at a specific age in childhood.