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      Patterns of Psychiatric Comorbidity and Genetic Correlations Provide New Insights Into Differences Between Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

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          Abstract

          BACKGROUND:

          Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share common genetic factors but seem to have specific patterns of psychiatric comorbidities. There are few systematic studies on adults; therefore, we compared psychiatric comorbidities in adults with these two neurodevelopmental disorders using population-based data and analyzed their genetic correlations to evaluate underlying factors.

          METHODS:

          Using data from Norwegian registries, we assessed patterns of psychiatric disorders in adults with ADHD (n = 38,636; 2.3%), ASD (n = 7528; 0.4%), and both diagnoses (n = 1467; 0.1%) compared with the remaining adult population (n = 1,653,575). We calculated their prevalence ratios (PRs) and differences using Poisson regression, also examining sex-specific relations. Genetic correlations (r g) among ADHD, ASD, and the examined psychiatric disorders were calculated by linkage disequilibrium score regression, exploiting summary statistics from relevant genome-wide association studies.

          RESULTS:

          For all psychiatric comorbidities, PRs differed between ADHD and ASD. Associations were strongest in individuals with ADHD and ADHD+ASD for most comorbidities, in both men and women. The relative prevalence increase of substance use disorder was three times larger in ADHD than in ASD (PR ADHD, 6.2; 95% confidence interval [CI], 6.1–6.4; PR ASD, 1.9; 95% CI, 1.7–2.2; p<.001); however, the opposite was true for schizophrenia (PR ASD,13.9; 95% CI, 12.7–15.2; PR ADHD, 4.4; 95% CI, 4.1–4.7; p<.001). Genetic correlations supported these patterns but were significantly different between ADHD and ASD only for the substance use disorder proxies and personality traits ( p<.006 for all).

          CONCLUSIONS:

          Adults with ADHD, ASD, or both ADHD and ASD have specific patterns of psychiatric comorbidities. This may partly be explained by differences in underlying genetic factors.

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          Most cited references61

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          Multiple imputation by chained equations: what is it and how does it work?

          Multivariate imputation by chained equations (MICE) has emerged as a principled method of dealing with missing data. Despite properties that make MICE particularly useful for large imputation procedures and advances in software development that now make it accessible to many researchers, many psychiatric researchers have not been trained in these methods and few practical resources exist to guide researchers in the implementation of this technique. This paper provides an introduction to the MICE method with a focus on practical aspects and challenges in using this method. A brief review of software programs available to implement MICE and then analyze multiply imputed data is also provided.
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            The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication.

            Despite growing interest in adult attention deficit hyperactivity disorder (ADHD), little is known about its prevalence or correlates. A screen for adult ADHD was included in a probability subsample (N=3,199) of 18-44-year-old respondents in the National Comorbidity Survey Replication, a nationally representative household survey that used a lay-administered diagnostic interview to assess a wide range of DSM-IV disorders. Blinded clinical follow-up interviews of adult ADHD were carried out with 154 respondents, oversampling those with positive screen results. Multiple imputation was used to estimate prevalence and correlates of clinician-assessed adult ADHD. The estimated prevalence of current adult ADHD was 4.4%. Significant correlates included being male, previously married, unemployed, and non-Hispanic white. Adult ADHD was highly comorbid with many other DSM-IV disorders assessed in the survey and was associated with substantial role impairment. The majority of cases were untreated, although many individuals had obtained treatment for other comorbid mental and substance-related disorders. Efforts are needed to increase the detection and treatment of adult ADHD. Research is needed to determine whether effective treatment would reduce the onset, persistence, and severity of disorders that co-occur with adult ADHD.
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              Attention-deficit/hyperactivity disorder.

              Attention-deficit/hyperactivity disorder (ADHD) is a persistent neurodevelopmental disorder that affects 5% of children and adolescents and 2.5% of adults worldwide. Throughout an individual's lifetime, ADHD can increase the risk of other psychiatric disorders, educational and occupational failure, accidents, criminality, social disability and addictions. No single risk factor is necessary or sufficient to cause ADHD. In most cases ADHD arises from several genetic and environmental risk factors that each have a small individual effect and act together to increase susceptibility. The multifactorial causation of ADHD is consistent with the heterogeneity of the disorder, which is shown by its extensive psychiatric co-morbidity, its multiple domains of neurocognitive impairment and the wide range of structural and functional brain anomalies associated with it. The diagnosis of ADHD is reliable and valid when evaluated with standard criteria for psychiatric disorders. Rating scales and clinical interviews facilitate diagnosis and aid screening. The expression of symptoms varies as a function of patient developmental stage and social and academic contexts. Although there are no curative treatments for ADHD, evidenced-based treatments can markedly reduce its symptoms and associated impairments. For example, medications are efficacious and normally well tolerated, and various non-pharmacological approaches are also valuable. Ongoing clinical and neurobiological research holds the promise of advancing diagnostic and therapeutic approaches to ADHD. For an illustrated summary of this Primer, visit: http://go.nature.com/J6jiwl.
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                Author and article information

                Journal
                0213264
                1117
                Biol Psychiatry
                Biol. Psychiatry
                Biological psychiatry
                0006-3223
                1873-2402
                22 June 2019
                28 April 2019
                15 October 2019
                15 October 2020
                : 86
                : 8
                : 587-598
                Affiliations
                Department of Biomedicine (BSS, TZ, AH, JH), Department of Global Public Health and Primary Care (BSS, AE, KK), K.G. Jebsen Centre for Neuropsychiatric Disorders (BSS, TZ, M-BP, AH, JH, KK), and Department of Clinical Medicine (M-BP), University of Bergen; Department of Psychiatry (M-BP, AH, JH), Haukeland University Hospital; and Division of Mental and Physical Health (AE, KK), Norwegian Institute of Public Health, Bergen, Norway; and the Analytic and Translational Genetics Unit (TZ), Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston; and Stanley Center for Psychiatric Research (TZ), Broad Institute of MIT and Harvard, Cambridge, Massachusetts.
                Author notes
                Address correspondence to Berit Skretting Solberg, M.D., Department of Biomedicine, K.G. Jebsen Center for Neuropsychiatric Disorders, University of Bergen, Jonas Lies vei 91, 5009 Bergen, Norway; bssol2004@ 123456yahoo.no .
                Article
                NIHMS1528109
                10.1016/j.biopsych.2019.04.021
                6764861
                31182215
                3d6351ed-2908-4bf6-ae04-71905b46fb52

                This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

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                Categories
                Article

                Clinical Psychology & Psychiatry
                adhd,asd,genetics,psychiatric comorbidity,schizophrenia,sud
                Clinical Psychology & Psychiatry
                adhd, asd, genetics, psychiatric comorbidity, schizophrenia, sud

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