Childhood-onset Attention Deficit Hyperactivity Disorder Research Articles

Compared Profile of Late-Onset Versus Childhood-Onset ADHD: A Case-Control Study Among Treatment-Seeking Adult Patients.

To compare the characteristics of childhood-onset versus late-onset Attention Deficit Hyperactivity Disorder (ADHD) in a sample of treatment-seeking patients. Among total of 101 adult patients who were recently diagnosed for ADHD, using the Diagnostic Interview for Adult ADHD (DIVA 2.0), 56 subjects exhibited childhood-onset ADHD, versus 45 displayed late-onset ADHD. Both groups were compared according to their sociodemographic, clinical, and neuropsychological features, providing crude (OR) and adjusted odds ratios (aOR), and their 95% confidence intervals [95% CI]. Compared to late-onset ADHD, patients with childhood-onset had a lower educational score, (OR = 0.52; 95% CI [0.35, 0.76]), a greater score of impulsivity (aOR = 1.09; 95% CI [1.03, 1.16]), an increased number of hyperactive-impulsive ADHD symptoms (aOR = 1.9; 95% CI [1.46, 2.47]), and higher rates childhood trauma (aOR = 1.07; 95% CI [1.01, 1.13]), cannabis use disorder (aOR = 1.07; 95% CI [1.01, 1.13]), and working memory impairment. No difference was observed concerning age, sex, psychiatric symptoms, quality of life, and autonomy. Childhood-onset adult ADHD displayed a more severe profile, relative to late-onset ADHD.

The stability and persistence of symptoms in childhood-onset ADHD.

The course of childhood-onset attention deficit hyperactivity disorder (ADHD) varies across individuals; some will experience persistent symptoms while others' symptoms fluctuate or remit. We describe the longitudinal course of ADHD symptoms and associated clinical characteristics in adolescents with childhood-onset ADHD. Participants (aged 6-12 at baseline) from the Longitudinal Assessment of Manic Symptoms (LAMS) study who met DSM criteria for ADHD prior to age 12 were evaluated annually with the Kiddie Schedule for Affective Disorders and Schizophrenia for eight years. At each timepoint, participants were categorized as meeting ADHD criteria, subthreshold criteria, or not havingADHD. Stability of course was defined by whether participants experienced consistent ADHD symptoms, fluctuating symptoms, or remission. The persistence of the symptoms was defined by symptom status at the final two follow-ups (stable ADHD, stable remission, stable partial remission, unstable). Of 685 baseline participants, 431 had childhood-onset ADHD and at least two follow-ups. Half had a consistent course of ADHD, nearly 40% had a remitting course, and the remaining participants had a fluctuating course. More than half of participants met criteria for ADHD at the end of their participation; about 30% demonstrated stable full remission, 15% had unstable symptoms, and one had stable partial remission. Participants with a persistent course and stable ADHD outcome reported the highest number of symptoms and were most impaired. This work builds on earlier studies that describe fluctuating symptoms in young people with childhood-onset ADHD. Results emphasize the importance of ongoing monitoring and detailed assessment of factors likely to influence course and outcome to help young people with childhood-onset ADHD.

Neurocognitive markers of late‐onset ADHD: a 6‐year longitudinal study

There is an increased interest in 'late-onset' attention-deficit/hyperactivity disorder (ADHD), referring to the onset of clinically significant ADHD symptoms after the age of 12years. This study aimed to examine whether unaffected siblings with late-onset ADHD could be differentiated from stable unaffected siblings by their neurocognitive functioning in childhood. We report findings from a 6-year prospective, longitudinal study of the Dutch part of the International Multicenter ADHD Genetics (IMAGE) study, including individuals with childhood-onset (persistent) ADHD (n=193), their siblings with late-onset ADHD (n=34), their stable unaffected siblings (n=111) and healthy controls (n=186). At study entry (mean age: 11.3) and follow-up (mean age: 17.01), participants were assessed for ADHD by structured psychiatric interviews and multi-informant questionnaires. Several neurocognitive functions were assessed at baseline and after 6years, including time reproduction, timing variability (reaction time variability and time production variability), reaction time speed, motor control and working memory; intelligence was taken as a measure of overall neurocognitive functioning. Siblings with late-onset ADHD were similar to individuals with childhood-onset ADHD in showing longer reaction times and/or higher error rates on all neurocognitive measures at baseline and follow-up, when compared to healthy controls. They differed from stable unaffected siblings (who were similar to healthy controls) by greater reaction time variability and timing production variability at baseline. No significant group by time interaction was found for any of the tasks. For unaffected siblings of individuals with ADHD, reaction time variability and timing production variability may serve as neurocognitive marker for late-onset ADHD.

Multimodal neuroimaging-based prediction of adult outcomes in childhood-onset ADHD using ensemble learning techniques.

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent and heterogeneous neurodevelopmental disorder, which is diagnosed using subjective symptom reports. Machine learning classifiers have been utilized to assist in the development of neuroimaging-based biomarkers for objective diagnosis of ADHD. However, existing basic model-based studies in ADHD report suboptimal classification performances and inconclusive results, mainly due to the limited flexibility for each type of basic classifier to appropriately handle multi-dimensional source features with varying properties. This study applied ensemble learning techniques (ELTs), a meta-algorithm that combine several basic machine learning models into one predictive model in order to decrease variance, bias, or improve predictions, in multimodal neuroimaging data collected from 72 young adults, including 36 probands (18 remitters and 18 persisters of childhood ADHD) and 36 group-matched controls. All currently available optimization strategies for ELTs (i.e., voting, bagging, boosting and stacking techniques) were tested in a pool of semifinal classification results generated by seven basic classifiers. The high-dimensional neuroimaging features for classification included regional cortical gray matter (GM) thickness and surface area, GM volume of subcortical structures, volume and fractional anisotropy of major white matter fiber tracts, pair-wise regional connectivity and global/nodal topological properties of the functional brain network for cue-evoked attention process. As a result, the bagging-based ELT with the base model of support vector machine achieved the best results, with significant improvement of the area under the receiver of operating characteristic curve (0.89 for ADHD vs. controls and 0.9 for ADHD persisters vs. remitters). Features of nodal efficiency in right inferior frontal gyrus, right middle frontal (MFG)-inferior parietal (IPL) functional connectivity, and right amygdala volume significantly contributed to accurate discrimination between ADHD probands and controls; higher nodal efficiency of right MFG greatly contributed to inattentive and hyperactive/impulsive symptom remission, while higher right MFG-IPL functional connectivity strongly linked to symptom persistence in adults with childhood ADHD. Considering their improved robustness than the commonly implemented basic classifiers, findings suggest that ELTs may have the potential to identify more reliable neurobiological markers for neurodevelopmental disorders.

ADHD symptoms map onto noise-driven structure-function decoupling between hub and peripheral brain regions.

Adults with childhood-onset attention-deficit hyperactivity disorder (ADHD) show altered whole-brain connectivity. However, the relationship between structural and functional brain abnormalities, the implications for the development of life-long debilitating symptoms, and the underlying mechanisms remain uncharted. We recruited a unique sample of 80 medication-naive adults with a clinical diagnosis of childhood-onset ADHD without psychiatric comorbidities, and 123 age-, sex-, and intelligence-matched healthy controls. Structural and functional connectivity matrices were derived from diffusion spectrum imaging and multi-echo resting-state functional MRI data. Hub, feeder, and local connections were defined using diffusion data. Individual-level measures of structural connectivity and structure-function coupling were used to contrast groups and link behavior to brain abnormalities. Computational modeling was used to test possible neural mechanisms underpinning observed group differences in the structure-function coupling. Structural connectivity did not significantly differ between groups but, relative to controls, ADHD showed a reduction in structure-function coupling in feeder connections linking hubs with peripheral regions. This abnormality involved connections linking fronto-parietal control systems with sensory networks. Crucially, lower structure-function coupling was associated with higher ADHD symptoms. Results from our computational model further suggest that the observed structure-function decoupling in ADHD is driven by heterogeneity in neural noise variability across brain regions. By highlighting a neural cause of a clinically meaningful breakdown in the structure-function relationship, our work provides novel information on the nature of chronic ADHD. The current results encourage future work assessing the genetic and neurobiological underpinnings of neural noise in ADHD, particularly in brain regions encompassed by fronto-parietal systems.

Annual Research Review: Does late-onset attention-deficit/hyperactivity disorder exist?

Attention-deficit/hyperactivity disorder (ADHD) is conceptualized as an early onset childhood neurodevelopmental disorder. Prevalence in adults is around two-thirds that in childhood, yet longitudinal outcome studies of children with ADHD found a minority continue to meet full criteria in adulthood. This suggests that not all adult cases meet ADHD criteria as children, a conclusion supported by earlier studies relying on retrospective recall in adolescent and adult samples. More recently prospective follow-up of population and control samples suggest that adolescent and young adult ADHD is not always a continuation of childhood ADHD. Here, we review the literature on age of onset, to explore whether late-onset ADHD exists, and if so, examine the evidence for whether this should be considered the same or a different disorder as childhood onset ADHD. We conclude that current evidence supports the view that a significant proportion of young adults meeting criteria for ADHD would not have met full diagnostic criteria for ADHD as children. However, many in the late-onset group show some ADHD symptoms in childhood, or an externalizing disorder such as oppositional defiant disorder. Furthermore, the current studies suggest that most (but not all) cases of late-onset ADHD develop the disorder between the ages of 12-16 and can therefore be considered adolescent or early adult onset ADHD. There is a relative lack of data spanning young to older adulthood to address the question of adult-onset. Currently, there is insufficient data to clarify the extent to which early and late onset ADHD reflect a different balance of genetic and environmental risks or share the same underlying neural mechanisms. Clinicians should be aware that significantly impairing forms of ADHD can emerge beyond the age of 12years, although perhaps rarely in the context of a complete absence of precursors. The current evidence on treatment responses is limited.

Hyperactivity/restlessness is associated with increased functional connectivity in adults with ADHD: a dimensional analysis of resting state fMRI

BackgroundAdult attention-deficit/hyperactivity disorder (ADHD) is a serious and frequent psychiatric disorder of multifactorial pathogenesis. Several lines of evidence support the idea that ADHD is, in its core, a disorder of dysfunctional brain connectivity within and between several neurofunctional networks. The primary aim of this study was to investigate associations between the functional connectivity within resting state brain networks and the individual severity of core ADHD symptoms (inattention, hyperactivity, and impulsivity).MethodsResting state functional magnetic resonance imaging (rs-fMRI) data of 38 methylphenidate-naïve adults with childhood-onset ADHD (20 women, mean age 40.5 years) were analyzed using independent component analysis (FSL’s MELODIC) and FSL’s dual regression technique. For motion correction, standard volume-realignment followed by independent component analysis-based automatic removal of motion artifacts (FSL’s ICA-AROMA) were employed. To identify well-established brain networks, the independent components found in the ADHD group were correlated with brain networks previously found in healthy participants (Smith et al. PNAS 2009;106:13040–5). To investigate associations between functional connectivity and individual symptom severity, sex, and age, linear regressions were performed.ResultsDecomposition of resting state brain activity of adults with ADHD resulted in similar resting state networks as previously described for healthy adults. No significant differences in functional connectivity were seen between women and men. Advanced age was associated with decreased functional connectivity in parts of the bilateral cingulate and paracingulate cortex within the executive control network. More severe hyperactivity was associated with increased functional connectivity in the left putamen, right caudate nucleus, right central operculum and a portion of the right postcentral gyrus within the auditory/sensorimotor network.ConclusionsThe present study supports and extends our knowledge on the involvement of the striatum in the pathophysiology of ADHD, in particular, in the pathogenesis of hyperactivity. Our results emphasize the usefulness of dimensional analyses in the study of ADHD, a highly heterogeneous disorder.Trial registrationISRCTN12722296 (https://doi.org/10.1186/ISRCTN12722296).

Neurobiological support to the diagnosis of ADHD in stimulant-naïve adults: pattern recognition analyses of MRI data.

In adulthood, the diagnosis of attention-deficit/hyperactivity disorder (ADHD) has been subject of recent controversy. We searched for a neuroanatomical signature associated with ADHD spectrum symptoms in adults by applying, for the first time, machine learning-based pattern classification methods to structural MRI and diffusion tensor imaging (DTI) data obtained from stimulant-naïve adults with childhood-onset ADHD and healthy controls (HC). Sixty-seven ADHD patients and 66 HC underwent high-resolution T1-weighted and DTI acquisitions. A support vector machine (SVM) classifier with a non-linear kernel was applied on multimodal image features extracted on regions of interest placed across the whole brain. The discrimination between a mixed-gender ADHD subgroup and individually matched HC (n = 58 each) yielded area-under-the-curve (AUC) and diagnostic accuracy (DA) values of up to 0.71% and 66% (P = 0.003) respectively. AUC and DA values increased to 0.74% and 74% (P = 0.0001) when analyses were restricted to males (52 ADHD vs. 44 HC). Although not at the level of clinically definitive DA, the neuroanatomical signature identified herein may provide additional, objective information that could influence treatment decisions in adults with ADHD spectrum symptoms.

Screening for attention deficit-hyperactivity disorder (ADHD) symptomatology in adult mental health clinics.

This study estimates the symptomatology of attention deficit-hyperactivity disorder (ADHD) in adult mental health services (AMHS) outpatient clinics. All consecutive patients attending any of the outpatients' clinics in Sligo/Leitrim AMHS were invited to participate. Participants completed the Adult ADHD Self-Report Scale (ASRS) and the Wender Utah Rating Scale (WURS) self-report. Clinical notes were reviewed to identify those with a pre-existing ADHD diagnosis. From 822 attending the clinics, 62 did not meet inclusion criteria, 97 declined to participate and 29 had incomplete data in either of the screening scales, leaving 634 (77%) eligible for full study analysis. Mean age was 40.38 (s.d.: 12.85), and 326 (51.4%) were females. In total, 215 (33.9%) screened positive on the WURS for childhood onset ADHD and 219 (34.5%) participants scored positive on the ASRS. Applying a more stringent criteria of scoring above cut-offs on both scales, suggested 131 (20.7%) screened positive on both. Only three (2.3%) had a prior clinical diagnosis. This preliminary study suggests the possibility of relatively higher rates of ADHD in a general AMHS than previously thought, however, given the possibility of overlapping symptoms with other major psychiatric disorders in adulthood and recall bias further research is needed before drawing firm conclusions.

Is adult-onset attention deficit/hyperactivity disorder frequent in clinical practice?

Recent population-based longitudinal studies concluded that most adults with attention deficit/hyperactivity disorder (ADHD) symptoms would not have a childhood history of ADHD, leading to the concept of adult-onset ADHD. In a large, well-characterized clinical population of 446 adults with a primary complaint of ADHD, we reported a low frequency of adult-onset ADHD (6.9%), being a primary isolated condition in 2.8%. They had less severe symptoms and tendencies for higher hypersomnolence disorder comorbidity than patients with typical childhood-onset ADHD. Our findings reinforce the requirement to exclude other disorders that might overlap with ADHD or mimic ADHD symptoms in adulthood onset patients.

Academic Achievement in Adults with a History of Childhood Attention-Deficit/Hyperactivity Disorder: A Population-Based Prospective Study.

Previous research on the developmental course of attention-deficit/hyperactivity disorder (ADHD) is limited by biased clinic-referred samples and other methodological problems. Thus, questions about adult academic outcomes associated with childhood ADHD remain unanswered. Thus, the objective of this study was to describe academic outcomes in adulthood among incident cases of research-identified childhood ADHD versus non-ADHD referents from a population-based birth cohort. Young adults with research-identified childhood ADHD (N = 232; mean age 27.0 yr; 72.0% men) and referents (N = 335; mean age 28.6 yr; 62.7% men) from a 1976 to 1982 birth cohort (N = 5699) were invited to participate in a followup study and were administered an academic achievement battery consisting of the basic reading component of the Woodcock-Johnson III Tests of Achievement (WJ-III) and the arithmetic subtest of the Wide Range Achievement Test-Third Edition (WRAT-3). Outcomes were compared between the 2 groups using linear regression models, adjusted for age, sex, and comorbid learning disability status. Childhood ADHD cases scored from 3 to 5 grade equivalents lower on all academic tests compared with referents, with mean (SD) standard scores of 95.7 (8.4) versus 101.8 (8.1) in basic reading; 95.0 (9.3) versus 101.9 (8.5) in letterword identification; 98.2 (8.6) versus 103.2 (9.2) in passage comprehension; 95.7 (9.1) versus 100.9 (9.0) in word attack; and 87.8 (12.9) versus 98.0 (12.0) in arithmetic. This is the first prospective, population-based study of adult academic outcomes of childhood ADHD. Our data provide evidence that childhood onset ADHD is associated with long-term underachievement in reading and math that may negatively impact ultimate educational attainment and occupational functioning in adulthood.

Can Attention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood?

In this issue of JAMAPsychiatry, 2 large, longitudinal, population studies from Brazil1 and the United Kingdom2 propose aparadigmatic shift in ourunderstandingof attention-deficit/ hyperactivity disorder (ADHD). They conclude, not only that theonsetofADHDcanoccur inadulthood,but that childhoodonset and adult-onset ADHDmay be distinct syndromes. Prior to thesepublications, thediagnosisofADHDinadults hadevolvedin2directions.Ameta-analysis3oflongitudinalstudiesdocumentedanage-dependentdecline in theexpressionof ADHDsymptoms.Two-thirds ofyouthwithADHDcontinued tohaveimpairingsymptomsof ADHDinyoungadulthood,despite only 15%meeting full diagnostic criteria for the disorder. TheBrazilianandUKstudies found theexpected rateofpersistence to ages 18 to 19 years: 17.2% and 21.9%%, respectively. A longitudinal population study4 from New Zealand observed a 4.9%persistencerateofADHDtoage38years.Practitioners take heed: these lowratesof casesmeeting fulldiagnostic criteria ignorethemuchhigherpersistencerateof impairingADHDsymptoms,which are relevant in clinical practice.3 In each study, the prevalence of adult-onset ADHD (Brazil, 10.3%1; UnitedKingdom, 5.5%2; andNewZealand, 2.7%4) wasmuch larger than theprevalenceof childhood-onset adult ADHD (United Kingdom, 2.6%; Brazil, 1.5%; and New Zealand, 0.3%). These estimates should be viewedwith caution. Theadults in theBrazil andUKstudieswereaged18 to 19years. That is too small a slice of adulthood to draw firm conclusions.Moreover, theratesofchildhood-onsetadultADHDseem too low.1All rates are below3.1%,which is the lower endof the 95% CI from a 10-country population study of adults.5 Why do the prospective studies of youth and population studies of adults disagree? One answer is the potential for recall biases in the latter studies.6 Another reason for disagreement is noted in theBrazilian study1: the “false-positive paradox.” This maxim states that, even when false-positive rates are low,many, or evenmost, diagnoses in a population study canbe false. For example, if theprevalenceofADHD is 5%and the false-positive rate is 5%, thenhalf thediagnoses in apopulation studywill be false. The false-positive rate is sensitive to the method of diagnosis. The child diagnoses in the studies fromBrazil,1 theUnitedKingdom,2 andNewZealand4used reports from parents and/or teachers, but the adult diagnoses were based on self-report. Self-reports of ADHD in adults are less reliable than informant reports, which is why the heritability of adult ADHD is low using self-reports but high using informant reports. In fact, theUKstudy foundavery lowheritability for adult ADHD (35%), which could be a sign of substantialmeasurementerrorandfalse-positivediagnoses.Of further concern, another longitudinal study6 found that current symptomsofADHDwereunderreportedbyadultswhohadhad ADHD in childhood and overreported by adults who did not haveADHD inchildhood.Because these concerns suggest that the UK, Brazilian, and New Zealand studies may have underestimated the persistence of ADHD and overestimated the prevalenceofadult-onsetADHD, itwouldbeamistake forpractitioners to assume that most adults referred to them with ADHD symptoms will not have a history of ADHD in youth. Theseconcernsdonotargueagainst theexistenceofadultonset ADHD or the idea that it is a clinically relevant syndrome. In fact, as a group, the adult-onset cases showed significant functional impairment. Moreover, one of the studies ruled out the idea that adult-onset ADHD is amisdiagnosis of another disorder. Further support for the validity of adultonset ADHD comes froma study of referred adultswho retrospectively reported childhood symptoms.7 Based on clinical features and familial transmission, that study concluded that onsetofADHDin lateadolescenceandearlyadulthood isvalid.7 The new articles proffer provocative conclusions: from Brazil,1 thatchildandadultADHDare“distinctsyndromes,”from theUnitedKingdom,2 “that adult ADHD ismore complex than a straightforward continuationof the childhooddisorder,” and fromNewZealand,4thatadultADHDis“notaneurodevelopmentaldisorder.”Theseconclusionsseempremature. Ineachstudy, adult-onset ADHD was de novo only in the sense that fullthresholdADHDhadnotbeendiagnosedby the investigatorsat priorassessments.IntheNewZealandstudy,comparedwithcontrols, theadult-onsetADHDgrouphadmoreteacher-ratedsymptoms of ADHD, more conduct disorder in childhood and were more likely to have had a combined parent-teacher report of ADHDsymptomonset prior to age 12 years. Likewise, the individuals in theadult-onsetADHDgroup in theUKstudyhadsignificantlyelevatedratesofADHDsymptoms, conductdisorder, andoppositionaldefiantdisorder inchildhood. In theBrazilian study,1 only 38% of participants with adult-onset ADHD were “neurotypical”asdefinedbyADHDandconductdisordersymptoms. Likewise, in a study of referred cases, one-third of lateadolescentandadult-onsetcaseshadchildhoodhistoriesofoppositionaldefiantdisorder,conductdisorder,andschoolfailure.7 Thus,many of the “adult onsets” of ADHD appear to have had neurodevelopmental roots. Theseneurodevelopmental rootspoint toanotherparadigm changerwhich, althoughnot discussed by these investigators, can be deduced from their data: the existence of subthreshold Related articles Opinion

Evaluation of the Persistence, Remission, and Emergence of Attention-Deficit/Hyperactivity Disorder in Young Adulthood.

Attention-deficit/hyperactivity disorder (ADHD) is now recognized to occur in adulthood and is associated with a range of negative outcomes. However, less is known about the prospective course of ADHD into adulthood, the risk factors for its persistence, and the possibility of its emergence in young adulthood in nonclinical populations. To investigate childhood risk factors and young adult functioning of individuals with persistent, remitted, and late-onset young adult ADHD. The study sample was the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in England and Wales from January 1, 1994, to December 4, 1995. Evaluation of childhood ADHD (ages 5, 7, 10, and 12 years) included prenatal and perinatal factors, clinical characteristics, and aspects of the family environment. Among participants aged 18 years, ADHD symptoms and associated impairment, overall functioning, and other mental health disorders were examined. Data analysis was conducted from February 19 to September 10, 2015. Attention-deficit/hyperactivity disorder according to DSM-IV diagnostic criteria in childhood and DSM-5 diagnostic criteria in young adulthood. Of 2232 participants in the E-Risk Study, 2040 were included in the present analysis. In total, 247 individuals met diagnostic criteria for childhood ADHD; of these, 54 (21.9%) also met diagnostic criteria for the disorder at age 18 years. Persistence was associated with more symptoms (odds ratio [OR], 1.11 [95% CI, 1.04-1.19]) and lower IQ (OR, 0.98 [95% CI, 0.95-1.00]). At age 18 years, individuals with persistent ADHD had more functional impairment (school/work: OR, 3.30 [95% CI, 2.18-5.00], home/with friends: OR, 6.26 [95% CI, 3.07-12.76]), generalized anxiety disorder (OR, 5.19 [95% CI, 2.01-13.38]), conduct disorder (OR, 2.03 [95% CI, 1.03-3.99]), and marijuana dependence (OR, 2.88 [95% CI, 1.07-7.71]) compared with those whose ADHD remitted. Among 166 individuals with adult ADHD, 112 (67.5%) did not meet criteria for ADHD at any assessment in childhood. Results from logistic regressions indicated that individuals with late-onset ADHD showed fewer externalizing problems (OR, 0.93 [95% CI, 0.91-0.96]) and higher IQ (OR, 1.04 [95% CI, 1.02-1.07]) in childhood compared with the persistent group. However, at age 18 years, those with late-onset ADHD demonstrated comparable ADHD symptoms and impairment as well as similarly elevated rates of mental health disorders. We identified heterogeneity in the DSM-5 young adult ADHD population such that this group consisted of a large, late-onset ADHD group with no childhood diagnosis, and a smaller group with persistent ADHD. The extent to which childhood-onset and late-onset adult ADHD may reflect different causes has implications for genetic studies and treatment of ADHD.

Characterising resting-state functional connectivity in a large sample of adults with ADHD

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood psychiatric disorder that often persists into adulthood. While several studies have identified altered functional connectivity in brain networks during rest in children with ADHD, few studies have been performed on adults with ADHD. Existing studies have generally investigated small samples. We therefore investigated aberrant functional connectivity in a large sample of adult patients with childhood-onset ADHD, using a data-driven, whole-brain approach. Adults with a clinical ADHD diagnosis (N=99) and healthy, adult comparison subjects (N=113) underwent a 9-minute resting-state fMRI session in a 1.5T MRI scanner. After elaborate preprocessing including a thorough head-motion correction procedure, group independent component analysis (ICA) was applied from which we identified six networks of interest: cerebellum, executive control, left and right frontoparietal and two default-mode networks. Participant-level network maps were obtained using dual-regression and tested for differences between patients with ADHD and controls using permutation testing. Patients showed significantly stronger connectivity in the anterior cingulate gyrus of the executive control network. Trends were also observed for stronger connectivity in the cerebellum network in ADHD patients compared to controls. However, there was considerable overlap in connectivity values between patients and controls, leading to relatively low effect sizes despite the large sample size. These effect sizes were slightly larger when testing for correlations between hyperactivity/impulsivity symptoms and connectivity strength in the executive control and cerebellum networks. This study provides important insights for studies on the neurobiology of adult ADHD; it shows that resting-state functional connectivity differences between adult patients and controls exist, but have smaller effect sizes than existing literature suggested.

Neurobiology of Adult ADHD: Emerging Evidence for Network Dysfunctions.

FIGURE 1. Changes in cortical thickness provide one measure of brain maturation. A large longitudinal study found that for most areas of cortex, children with attention deficit hyperactivity disorder (ADHD) reach peak cortical thickness several years later than typically developing children, supporting presence of developmental delay. The rate of cortical thinning also differed between the group who continued to meet diagnostic criteria into adulthood (persistent ADHD) and those who did not (remitted ADHD). Areas of cortex in which the rate of thinning correlated with adult symptom level (green, more symptoms associated with more thinning) are approximated on medial and lateral simplified representations of cortex. An earlier study also identified multiple areas in which cortex was thinner in adults with persistent ADHD compared with controls (orange). In addition, this study noted some areas of thicker cortex in remitted ADHD when compared with persistent ADHD (blue).

Isochromosome 13 in a patient with childhood-onset schizophrenia, ADHD, and motor tic disorder.

BackgroundA small percentage of all cases of schizophrenia have a childhood onset. The impact on the individual and family can be devastating. We report the results of genetic analyses from a patient with onset of visual hallucinations at 5 years, and a subsequent diagnosis at 9 years of schizophrenia, attention deficit hyperactivity disorder (ADHD) with hyperactivity and impulsivity, and chronic motor tic disorder.ResultsKaryotypic analysis found 45,XX,i(13)(q10) in all cells examined. Alpha satellite FISH of isochromosome 13 revealed a large unsplit centromeric region, interpreted as two centromeres separated by minimal or undetectable short-arm material or as a single monocentric centromere, indicating that the isochromosome likely formed post-zygotically by a short arm U-type or centromeric exchange. Characterization of chromosome 13 simple tandem repeats and Affymetrix whole-genome 6.0 SNP array hybridization found homozygosity for all markers, and the presence of only a single paternal allele in informative markers, consistent with an isodisomic isochromosome of paternal origin. Analysis of two chromosome 13 schizophrenia candidate genes, D-amino acid oxidase activator (DAOA) and 5-hydroxytryptamine (serotonin) receptor 2A (5-HTR2A), failed to identify non-synonymous coding mutations but did identify homozygous risk polymorphisms.ConclusionsWe report a female patient with childhood-onset schizophrenia, ADHD, and motor tic disorder associated with an isodisomic isochromosome 13 of paternal origin and a 45,XX,i(13)(q10q10) karyotype. We examined two potential mechanisms to explain chromosome 13 involvement in the patient's pathology, including reduction to homozygosity of a paternal mutation and reduction to homozygosity of a paternal copy number variation, but were unable to identify any overtly pathogenic abnormality. Future studies may consider whether epigenetic mechanisms resulting from uniparental disomy (UPD) and the lack of chromosome 13 maternal alleles lead to the patient's features.

Personality traits among ADHD adults: implications of late-onset and subthreshold diagnoses

Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish onset prior to the DSM-IV criterion of age 7 or if the number of symptoms does not achieve the DSM threshold for diagnosis. Previous work has assessed the validity of such diagnoses based on psychiatric co-morbidity, family history and neuropsychological functions but none of these studies have used personality as a validation criterion. We compared four groups of adults: (1) full ADHD subjects who met all DSM-IV criteria for childhood-onset ADHD; (2) late-onset subjects who met all criteria except the age at onset criterion, (3) subthreshold subjects who did not meet full symptom criteria and (4) non-ADHD subjects who did not meet any of the above criteria. Diagnoses were made by using the Structured Clinical Interview for DSM-IV (SCID) and the Temperament and Character Inventory (TCI) was used to assess personality traits. We found that full ADHD and late-onset ADHD showed similar personality profiles with significant deviations on all TCI scales except reward dependence and self-transcendence. By contrast, subthreshold cases only showed deviations on novelty seeking and self-directiveness. These data call into question the stringent age of onset of ADHD symptom criteria for adults when making retrospective diagnoses of ADHD. Subthreshold ADHD seems to be a milder form of the disorder that is consistent with dimensional views of the disorder.

Comorbidity of adult attention deficit hyperactivity disorder and its relation to executive functions in patients with antisocial personality disorder

Background: Main features of antisocial personality disorder (APD) are aggression, tendency to violence, poor frustration tolerance, impulsivity, difficulties in learning from experiences. Attention deficit hyperactivity disorder (ADHD) is characterized with difficulty to sustain attention, hyperactivity and impulsivity. Association between ADHD and violent behavior is well known. Childhood onset ADHD carries a high risk of persisting into adulthood as antisocial behaviors. Aim: In the present study, comorbidity of adult ADHD was screened in a group of patients with APD. Executive functions and attention were assessed by using neuropsychological test instruments. In addition, their relation to ADHD subtypes was investigated. Methods: A total of 90 male subjects with APD were included. Also, 90 ageand sex-matched healthy control subjects were involved into the study. The patients and control subjects were assessed by a semi-structured socio-demographic form, SCID-II, Turgay’s Adult ADHD Rating Scale, Wender Utah Rating Scale, Wisconsin Card Sorting Test, Stroop Test, Continuous Performance Test, and Trail-Making Test. Results: Comorbidity rate of adult ADHD was 83.3% in APD group while 6.7% of control subjects had a diagnosis of adult ADHD. The most frequently diagnosed ADHD subgroup was combined type in both APD and control group. In APD group, executive functions were significantly more deficient as compared to the control group. Among all ADHD subgroups, inattention subtype had the worst performance in neuropsychological assessments. Conclusion: Comorbidity of adult ADHD was quite common in APD subjects. Executive functions were generally deficient in APD patients with a co-diagnosis of adult ADHD.

Diagnosing Adult Attention Deficit Hyperactivity Disorder: Are Late Onset and Subthreshold Diagnoses Valid?

Diagnosing attention deficit hyperactivity disorder (ADHD) in adults is difficult when diagnosticians cannot establish an onset before the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve DSM's diagnosis threshold. The authors addressed the validity of DSM-IV's age-at-onset and symptom threshold criteria by comparing four groups of adults: 127 subjects with full ADHD who met all DSM-IV criteria for childhood-onset ADHD, 79 subjects with late-onset ADHD who met all criteria except the age-at-onset criterion, 41 subjects with subthreshold ADHD who did not meet full symptom criteria for ADHD, and 123 subjects without ADHD who did not meet any criteria. The authors hypothesized that subjects with late-onset and subthreshold ADHD would show patterns of psychiatric comorbidity, functional impairment, and familial transmission similar to those seen in subjects with full ADHD. Subjects with late-onset and full ADHD had similar patterns of psychiatric comorbidity, functional impairment, and familial transmission. Most children with late onset of ADHD (83%) were younger than 12. Subthreshold ADHD was milder and showed a different pattern of familial transmission than the other forms of ADHD. The data about the clinical features of probands and the pattern of transmission of ADHD among relatives found little evidence for the validity of subthreshold ADHD among such subjects, who reported a lifetime history of some symptoms that never met DSM-IV's threshold for diagnosis. In contrast, the results suggested that late-onset adult ADHD is valid and that DSM-IV's age-at-onset criterion is too stringent.

Neuropsychological Studies of Late Onset and Subthreshold Diagnoses of Adult Attention-Deficit/Hyperactivity Disorder

Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. We compared four groups of adults: 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except the age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder.