Project description:Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
Project description:BackgroundTactile sensitivity and sensory overload in ADHD are well-documented in clinical-, self-, and parent- reports, but empirical evidence is scarce and ambiguous and focuses primarily on children. Here, we compare both empirical and self-report tactile sensitivity and ADHD symptomatology in adults with ADHD and neurotypical controls. We evaluate whether tactile sensitivity and integration is more prevalent in ADHD and whether it is related to ADHD symptom severity.MethodsSomatosensory evoked potential (SEP) amplitudes were measured in 27 adults with ADHD and 24 controls during four conditions (rest, stroking of the own arm, stroking of the arm by a researcher, and stroking of an object). Participants also filled out questionnaires on tactile sensitivity and ADHD symptoms and performed a Qb-test as an objective measure of ADHD symptom severity.ResultsParticipants with ADHD self-reported greater tactile sensitivity and ADHD symptom severity than controls and received higher scores on the Qb-test. These values correlated with one another. ADHD participants showed lower tolerable threshold for electrical radial nerve stimulus, and greater reduction in cortical SEP amplitudes during additional tactile stimuli which was correlated with ADHD symptoms.ConclusionsWe find that ADHD symptomatology and touch sensitivity are directly linked, using both self-reports and experimental measures. We also find evidence of tactile sensory overload in ADHD, and an indication that this is linked to inattention specifically. Tactile sensitivity and sensory overload impact the functioning and life quality of many people with ADHD, and clinicians should consider this when treating their patients.
Project description:Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a long-term impact on functioning, productivity and quality of life of patients. This impact is largely due to the symptoms of inattentiveness. However, despite its impairing role in the lives of ADHD patients, inattentiveness has been studied relatively less frequently than have symptoms of impulsivity/hyperactivity and problems with executive function. This review therefore seeks to integrate the neuropsychological theories and current findings in the research fields of neuropsychology, neurophysiology, and neuroimaging, in an attempt to gain a more complete understanding of the role that inattentiveness plays in ADHD, as well as to suggest directions for future studies. The need for a more comprehensive understanding of inattentiveness and ADHD, which integrates findings from each of the three disciplines mentioned above, is emphasized.
Project description:Attention-deficit hyperactivity disorder (ADHD), like other psychiatric disorders, represents an evolving construct that has been refined and developed over the past several decades in response to research into its clinical nature and structure. The clinical presentation and course of the disorder have been extensively characterised. Efficacious medication-based treatments are available and widely used, often alongside complementary psychosocial approaches. However, their effectiveness has been questioned because they might not address the broader clinical needs of many individuals with ADHD, especially over the longer term. Non-pharmacological approaches to treatment have proven less effective than previously thought, whereas scientific and clinical studies are starting to fundamentally challenge current conceptions of the causes of ADHD in ways that might have the potential to alter clinical approaches in the future. In view of this, we first provide an account of the diagnosis, epidemiology, and treatment of ADHD from the perspective of both the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and the eleventh edition of the International Classification of Diseases. Second, we review the progress in our understanding of the causes and pathophysiology of ADHD on the basis of science over the past decade or so. Finally, using these discoveries, we explore some of the key challenges to both the current models and the treatment of ADHD, and the ways in which these findings can promote new perspectives.
Project description:Adult attention-deficit/hyperactivity disorder (ADHD) is common, but often undiagnosed. A valid and time-efficient screening tool for primary care is needed. Objective of this study is to evaluate the German version of the Adult ADHD Self-Report Scale for DSM-5 (ASRS-5) and its feasibility, acceptability, and reliability as a screening tool for adult ADHD in primary care. A multi-centered prospective, diagnostic study was performed. We recruited 262 patients in primary care practices and at an ADHD Outpatient Service of a department of psychiatry in Germany. Patients from 18 to 65 years with suspected or diagnosed ADHD were included by medical doctors, as well as non-ADHD patients as "negative controls." Participants filled in the ASRS-5 and a sociodemographic questionnaire. The Integrated Diagnosis of Adult ADHD, revised version (IDA-R) performed by trained interviewers was used for validation. Feasibility, acceptability, and credibility in primary care practices were examined through a semi-structured interview. The German version of the ASRS-5 showed comparable psychometric properties to the English original version (sensitivity 95.6% and specificity 72.3%). For factor structure, a parallel analysis suggested one latent dimension. Performing confirmatory factor analysis, the best fit was achieved for a general factor with one correlated error. Internal consistency results in Raykovs Omega = 0.86 and Cronbach's α = 0.88. The ASRS-5 was assessed positively in terms of feasibility, acceptability, and credibility by interviewed general practitioners. Potential problems were raised for "treatment options," "stigmatization," and "knowledge gaps." In conclusion, the German version of the ASRS-5 offers a promising tool to improve adult ADHD patients' diagnosis and healthcare.
Project description:ImportanceEvidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.ObjectiveTo examine the association between adult ADHD and the risk of dementia.Design, setting, and participantsThis prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.ExposureAdult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.Main outcome and measuresCox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.ResultsAt the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.Conclusions and relevanceIn this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.
Project description:Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.