Effect of Pharmacological Treatment of Attention-Deficit/Hyperactivity Disorder on Criminality.

OBJECTIVE: Criminality rates are higher among persons with attention-deficit/hyperactivity disorder (ADHD), and evidence that medication reduces crime is limited. Medication rates between clinics vary widely even within universal health care systems, partly because of providers' treatment preferences. We used this variation to estimate causal effects of pharmacological treatment of ADHD on 4-year criminal outcomes. METHOD: We used Norwegian population-level registry data to identify all unique patients aged 10 to 18 years diagnosed with ADHD between 2009 and 2011 (n = 5,624), their use of ADHD medication, and subsequent criminal charges. An instrumental variable design, exploiting variation in provider preference for ADHD medication between clinics, was used to identify causal effects of ADHD medication on crime among patients on the margin of treatment, that is, patients who receive treatment because of their provider's preference. RESULTS: Criminality was higher in patients with ADHD relative to the general population. Medication preference varied between clinics and strongly affected patients' treatment. Instrumental variable analyses supported a protective effect of pharmacological treatment on violence-related and public-order-related charges with numbers needed to treat of 14 and 8, respectively. There was no evidence for effects on drug-, traffic-, sexual-, or property-related charges. CONCLUSION: This is the first study to demonstrate causal effects of pharmacological treatment of ADHD on some types of crimes in a population-based natural experiment. Pharmacological treatment of ADHD reduced crime related to impulsive-reactive behavior in patients with ADHD on the margin of treatment. No effects were found on crimes requiring criminal intent, conspiracy, and planning. STUDY PREREGISTRATION INFORMATION: The ADHD controversy project: Long-term effects of ADHD medication; https://www.isrctn.com/; 11891971.

A systematic meta-review of systematic reviews on attention deficit hyperactivity disorder.

BACKGROUND: There are now hundreds of systematic reviews on attention deficit hyperactivity disorder (ADHD) of variable quality. To help navigate this literature, we have reviewed systematic reviews on any topic on ADHD. METHODS: We searched MEDLINE, PubMed, PsycINFO, Cochrane Library, and Web of Science and performed quality assessment according to the Joanna Briggs Institute Manual for Evidence Synthesis. A total of 231 systematic reviews and meta-analyses met the eligibility criteria. RESULTS: The prevalence of ADHD was 7.2% for children and adolescents and 2.5% for adults, though with major uncertainty due to methodological variation in the existing literature. There is evidence for both biological and social risk factors for ADHD, but this evidence is mostly correlational rather than causal due to confounding and reverse causality. There is strong evidence for the efficacy of pharmacological treatment on symptom reduction in the short-term, particularly for stimulants. However, there is limited evidence for the efficacy of pharmacotherapy in mitigating adverse life trajectories such as educational attainment, employment, substance abuse, injuries, suicides, crime, and comorbid mental and somatic conditions. Pharmacotherapy is linked with side effects like disturbed sleep, reduced appetite, and increased blood pressure, but less is known about potential adverse effects after long-term use. Evidence of the efficacy of nonpharmacological treatments is mixed. CONCLUSIONS: Despite hundreds of systematic reviews on ADHD, key questions are still unanswered. Evidence gaps remain as to a more accurate prevalence of ADHD, whether documented risk factors are causal, the efficacy of nonpharmacological treatments on any outcomes, and pharmacotherapy in mitigating the adverse outcomes associated with ADHD.

Effect of ADHD medication on risk of injuries: a preference-based instrumental variable analysis.

ADHD is associated with an increased risk of injury. Causal evidence for effects of pharmacological treatment on injuries is scarce. We estimated effects of ADHD medication on injuries using variation in provider preference as an instrumental variable (IV). Using Norwegian registry data, we followed 8051 patients who were diagnosed with ADHD aged 5 to 18 between 2009 and 2011 and recorded their ADHD medication and injuries treated in emergency rooms and emergency wards up to 4 years after diagnosis. Persons with ADHD had an increased risk of injuries compared to the general population (RR 1.35; 95% CI: 1.30-1.39), with higher risk in females (RR 1.47; 95% CI: 1.38-1.56) than males (RR 1.23; 95% CI: 1.18-1.28). The between-clinics variation in provider preference for ADHD medication was large and had a considerable impact on patients' treatment status. There was no causal evidence for protective effects of pharmacological treatment on injuries overall for young individuals with ADHD characterized by milder or atypical symptoms. However, there was an apparent effect of pharmacological treatment over time on the risk of injuries treated at emergency wards in this patient group.

Attention-deficit/hyperactivity disorder (ADHD) symptoms and their relation to diagnosed ADHD, sociodemographic characteristics, and substance use among patients receiving opioid agonist therapy: a Norwegian cohort study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) symptoms may challenge sufficient treatment of substance use and mental disorders. The literature on the extent of such symptoms among patients receiving opioid agonist therapy (OAT) is scarce. This study examined ADHD symptoms using the ADHD self-report scale (ASRS) and the association between the 'ASRS-memory' and 'ASRS-attention' scores and substance use and sociodemographic characteristics among patients receiving OAT. METHODS: We used data from assessment visits of a cohort of patients in Norway. In total, 701 patients were included from May 2017 to March 2022. All patients responded at least once to two ASRS questions assessing memory and attention, respectively. Ordinal regression analyses were performed to investigate whether the two obtained scores were associated with age, sex, frequent substance use, injecting use, housing status, and educational attainment at baseline, i.e., the first assessment, and over time. The results are presented as odds ratios (OR) with 95% confidence intervals (CI). Additionally, a subsample of 225 patients completed an extended interview, including the ASRS-screener and collection of registered mental disorder diagnoses from the medical records. Standard cutoffs were used to define the presence of each ASRS symptom or a positive ASRS-screener ('ASRS-positive'). RESULTS: At baseline, 428 (61%) and 307 (53%) patients scored over the cutoffs on the 'ASRS-memory' and 'ASRS-attention,' respectively. Frequent cannabis use was associated with higher 'ASRS-memory' (OR: 1.7, 95% CI: 1.1-2.6) and 'ASRS-attention' (1.7, 1.1-2.5) scores compared with less or no use at baseline, though reduced score on the 'ASRS-memory' over time (0.7, 0.6-1.0). At baseline, frequent stimulant use (1.8, 1.0-3.2) and low educational attainment (0.1, 0.0-0.8) were associated with higher 'ASRS-memory' scores. In the subsample fulfilling the ASRS-screener, 45% of the patients were 'ASRS-positive,' of whom 13% with a registered ADHD diagnosis. CONCLUSIONS: Our findings illustrate a relationship between the ASRS-memory and -attention scores and frequent cannabis and stimulant use. Furthermore, nearly half of the subsample was 'ASRS-positive.' Patients receiving OAT might benefit from being further assessed for ADHD, but improved diagnostic methods are required.

Geographical variation in ADHD: do diagnoses reflect symptom levels?

Rates of ADHD diagnosis vary across regions in many countries. However, no prior study has investigated how much within-country geographic variation in ADHD diagnoses is explained by variation in ADHD symptom levels. We examine whether ADHD symptom levels explain variation in ADHD diagnoses among children and adolescents using nationwide survey and register data in Norway. Geographical variation in incidence of ADHD diagnosis was measured using Norwegian registry data from the child and adolescent mental health services for 2011-2016. Geographical variation in ADHD symptom levels in clinics' catchment areas was measured using data from the Norwegian mother, father and child cohort study for 2011-2016 (n = 39,850). Cross-sectional associations between ADHD symptom levels and the incidence of ADHD diagnoses were assessed with fractional response models. Geographical variation in ADHD diagnosis rates is much larger than what can be explained by geographical variation in ADHD symptoms levels. Treatment in the Norwegian child and adolescent mental health services is free, universally available upon referral, and practically without competition from the private sector. Factors beyond health care access and unequal symptom levels seem responsible for the geographical variation in ADHD diagnosis.

Variation in attitudes toward diagnosis and medication of ADHD: a survey among clinicians in the Norwegian child and adolescent mental health services.

Prevalence and medication rates of ADHD vary geographically, both between and within countries. No absolute cutoff exists between ADHD and normal behavior, making clinician attitudes (leading to local practice cultures) a potential explanation for the observed variation in diagnosis and medication rates. The objective of this study was to describe variation in attitudes toward diagnosis and medication of ADHD among clinicians working in child and adolescent mental health services (CAMHS). We hypothesized that attitudes would vary along a spectrum from "restrictive" to "liberal". We also explored whether differences in attitudes between clinicians were related to professional background and workplace (clinic). A survey in the form of a web-based questionnaire was developed. All CAMHS outpatient clinics in Norway were invited. Potential respondents were all clinicians involved in diagnosing and treating children and adolescents with ADHD. To investigate the existence of attitudes toward diagnosis and medication as latent constructs, we applied confirmatory factor analysis (CFA). We further examined how much of variance in attitudes could be ascribed to profession and clinics by estimating intraclass correlation coefficients. In total, 674 respondents representing 77 (88%) of the clinics participated. We confirmed variation in attitudes with average responses leaning toward the "restrictive" end of the spectrum. CFA supported "attitude toward diagnosis" and "attitude toward medication" as separate, and moderately correlated (r = 0.4) latent variables, representing a scale from restrictive to liberal. Professional background and workplace explained only a small part of variance in these attitudes.

Dialectical behavioral therapy-based group treatment versus treatment as usual for adults with attention-deficit hyperactivity disorder: a multicenter randomized controlled trial.

BACKGROUND: Studies on structured skills training groups have indicated beneficial, although still inconclusive, effects on core symptoms of ADHD in adults. This trial examined effects of Dialectical Behavioral Therapy-based group treatment (DBT-bGT) on the broader and clinically relevant executive functioning and emotional regulation in adults with ADHD. METHODS: In a multicenter randomized controlled trial, adult patients with ADHD were randomly assigned to receive either weekly DBT-bGT or treatment as usual (TAU) during 14 weeks. Subsequently, participants receiving TAU were offered DBT-bGT. All were reassessed six months after ended DBT-bGT. Primary outcomes were the Behavior Rating Inventory of Executive Function (BRIEF-A) and the Difficulties in Emotion Regulation Scale (DERS). Secondary outcomes included self-reported ADHD-symptoms, depressive and anxiety symptoms, and quality of life. We used independent samples t- tests to compare the mean difference of change from pre- to post-treatment between the two treatment groups, and univariate linear models adjusting for differences between sites. RESULTS: In total, 121 participants (68 females), mean age 37 years, from seven outpatient clinics were included, of whom 104 (86%) completed the 14-week trial. Entering the study, 63% used medication for ADHD. Compared to TAU (n = 54), patients initially completing DBT-bGT (n = 50) had a significantly larger mean reduction on the BRIEF-A (-12.8 versus -0.37, P = 0.005, effect size 0.64), and all secondary outcomes, except for symptoms of anxiety. All significant improvements persisted at 6 months follow-up. Change on DERS did not differ significantly between the groups after 14 weeks, but scores continued to decrease between end of group-treatment and follow-up. CONCLUSIONS: This DBT-bGT was superior to TAU in reducing executive dysfunction, core symptoms of ADHD and in improving quality of life in adults with ADHD. Improvements sustained six months after ended treatment. The feasibility and results of this study provide evidence for this group treatment as a suitable non-pharmacological treatment option for adults with ADHD in ordinary clinical settings. TRIAL REGISTRATIONS: The study was pre-registered in the ISRCTN registry (identification number ISRCTN30469893, date February 19th 2016) and at the ClinicalTrials.gov (ID: NCT02685254, date February 18th 2016).

Goal management training improves executive control in adults with ADHD: an open trial employing attention network theory to examine effects on attention.

BACKGROUND: Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) typically experience poorer attentional control. According to the attention network theory, attentional control relies on three interacting networks of alerting, orienting, and executive control. In ADHD, it is mainly the alerting and executive control networks that are suggested and found to be compromised. METHODS: In the current study, we investigated if a group-based metacognitive remediation program (Goal Management Training [GMT]) in adults with ADHD would enhance attentional control using an experimental measure of the attention network theory. We expected that GMT would specifically enhance the executive control and alerting networks. RESULTS: Data from post- and follow up-assessments of 21 adults (age: 39.05 [11.93]) with ADHD who had completed GMT were included. Linear mixed-effects modeling revealed significant improvements in the functioning of the executive control network for the majority of the participants, although a small subset of participants showed a negative development following the intervention. Results also showed an improvement in the orienting network at follow up, but no change in the alerting network. CONCLUSION: The results may indicate that improvements in the functioning of the executive control network are central to the positive effects of GMT reported in disorders characterized by impaired attentional control. TRIAL REGISTRATION: The study was retrospectively registered in the ISRCTN (Identifier: ISRCTN91988877) on the 18/01/2021.

An Exploratory Investigation of Goal Management Training in Adults With ADHD: Improvements in Inhibition and Everyday Functioning.

Background: Adults with attention deficit/hyperactivity disorder (ADHD) are predominantly treated with medication. However, there is also a need for effective, psychologically based interventions. As ADHD is strongly associated with reduced inhibitory control, cognitive remediation approaches should be efficient. Goal management training (GMT) aims at enhancing inhibitory control and has shown positive effects on inhibitory control in non-ADHD patient groups. The aim of the current study was to explore whether GMT would specifically enhance inhibitory control in adults with ADHD, and if such an enhancement would lead to secondary improvements in self-reported everyday functioning. Methods: Twenty-one participants with ADHD (mean age: 39.05 years [SD 11.93]) completed the intervention and assessments pre-, post- and 6 months after the intervention. Measures included neuropsychological tests and self-report questionnaires pertaining to cognitive- and executive functioning, emotion regulation, quality of life, and ADHD symptoms. Results: Compared to baseline, the participants showed enhanced inhibitory control on performance-based measures at post-assessment and 6-month follow-up. The participants also reported increased productivity and reduced cognitive difficulties in everyday life at both assessments post-treatment, as well as improvements in aspects of emotion regulation and a reduction in the severity of core ADHD-symptoms at 6-month follow-up. Conclusion: Our exploratory study showed that GMT seems to specifically improve one of the core executive dysfunctions in ADHD, namely inhibitory control, with a positive effect lasting at least 6 months post-treatment. The adults with ADHD also reported improved self-regulation in their everyday life after completing GMT, providing strong arguments for further investigations of GMT as a treatment option for this group of adults. Clinical Trial Registration: The study is registered under ISRCTN.com (ISRCTN91988877; https://doi.org/10.1186/ISRCTN91988877).

Causal modelling of variation in clinical practice and long-term outcomes of ADHD using Norwegian registry data: the ADHD controversy project.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is among the most common mental disorders in children and adolescents, and it is a strong risk factor for several adverse psychosocial outcomes over the lifespan. There are large between-country and within-country variations in diagnosis and medication rates. Due to ethical and practical considerations, a few studies have examined the effects of receiving a diagnosis, and there is a lack of research on effects of medication on long-term outcomes.Our project has four aims organised in four work packages: (WP1) To examine the prognosis of ADHD (with and without medication) compared with patients with other psychiatric diagnoses, patients in contact with public sector child and adolescent psychiatric outpatient clinics (without diagnosis) and the general population; (WP2) Examine within-country variation in ADHD diagnoses and medication rates by clinics' catchment area; and(WP3) Identify causal effects of being diagnosed with ADHD and (WP4) ADHD medication on long-term outcomes. METHOD AND ANALYSIS: Our project links several nationwide Norwegian registries. The patient sample is all persons aged 5-18 years that were in contact with public sector child and adolescent psychiatric outpatient clinics in 2009-2011. Our comparative analysis of prognosis will be based on survival analysis and mixed-effects models. Our analysis of variation will apply mixed-effects models and generalised linear models. We have two identification strategies for the effect of being diagnosed with ADHD and of receiving medication on long-term outcomes. Both strategies rely on using preference-based instrumental variables, which in our project are based on provider preferences for ADHD diagnosis and medication. ETHICS AND DISSEMINATION: The project is approved by the Regional Ethics Committee, Norway (REC number 2017/2150/REC south-east D). All papers will be published in open-access journals and results will be presented in national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN11573246 and ISRCTN11891971.

Sex differences in parent-offspring recurrence of attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder sharing genetic risk factors with other common psychiatric disorders. However, intergenerational recurrence patterns of ADHD from parents to sons and daughters are not known. We aimed to examine the risk of ADHD in offspring of parents with ADHD and parents with other psychiatric disorders by parental and offspring sex, using parents without the specific disorders as comparison. METHODS: In a generation study linking data from several population-based registries, all Norwegians born 1967-2011 (n = 2,486,088; Medical Birth Registry of Norway) and their parents were followed to 2015. To estimate intergenerational recurrence risk, we calculated prevalence differences (PD) and the relative risk (RR) of ADHD in offspring by parental ADHD, bipolar disorder (BD), schizophrenia spectrum disorder (SCZ), major depression (MDD), all by parental and offspring sex. RESULTS: The absolute prevalence of ADHD in offspring of parents with ADHD was very high, especially in sons of two affected parents (41.5% and 25.1% in sons and daughters, respectively), and far higher than in offspring of parents with BD, SCZ or MDD. Intergenerational recurrence risks were higher for maternal than paternal ADHD (RRmaternal 8.4, 95% confidence interval (CI) 8.2-8.6 vs. RRpaternal 6.2, 6.0-6.4) and this was also true on the absolute scale (PDmaternal 21.1% (20.5-21.7) vs. PDpaternal 14.8% (14.3-15.4)). RRs were higher in daughters, while PDs higher in sons. Parental SCZ, BD and MDD were associated with an approximately doubled risk of offspring ADHD compared to parents without the respective disorders, and estimates did not differ significantly between daughters and sons. CONCLUSIONS: The intergenerational recurrence risks of ADHD were high and higher from mothers with ADHD than fathers with ADHD. Other parental psychiatric disorders also conferred increased risk of offspring ADHD, but far lower, indicating a sex- and diagnosis-specific intergenerational recurrence risk in parents with ADHD.

Potentially addictive drugs dispensing to patients receiving opioid agonist therapy: a register-based prospective cohort study in Norway and Sweden from 2015 to 2017.

OBJECTIVES: To compare the use of benzodiazepines, z-hypnotics, gabapentinoids, opioids and centrally acting stimulants (CAS) among patients who had received opioid agonist therapy (OAT) in Norway and Sweden during the period 2015 - 2017. DESIGN: A register-based prospective cohort study using information about dispensed drugs from the Norwegian Prescription Database and Swedish Prescribed Drug Register. SETTING: Patients who were dispensed OAT opioids from pharmacies. PARTICIPANTS: A total of 7176 Norwegian and 3591 Swedish patients on OAT were included. OUTCOME MEASURES: The number and frequency of potentially addictive drugs dispensed were calculated for the two countries. The mean daily doses of dispensed benzodiazepines and z-hypnotics were summarised by calculating benzodiazepines in diazepam equivalents and z-hypnotics in zopiclone equivalents. RESULTS: In 2017, 46% of patients in Norway, and 15% in Sweden, were dispensed a benzodiazepine. Moreover, 14% in Norway and 26% in Sweden received z-hypnotics. Gabapentinoids were dispensed to 10% of patients in Norway and 19% of patients in Sweden. In Norway, 6% and 12% of the patients received strong and weak non-OAT opioids, respectively, whereas in Sweden 10% were dispensed strong non-OAT opioids and 5% weak non-OAT opioids . CAS were dispensed to 4% in Norway and 18% in Sweden. The mean daily doses of benzodiazepines were 16 and 17 mg diazepam equivalents in Norway and Sweden, respectively. For z-hypnotics, the mean daily dose was 8 mg zopiclone equivalents in both countries. 'Benzodiazepines and z-hypnotics' was the most dispensed drug combination in 2017. Similar results were found in 2015 and 2016. CONCLUSIONS: Nearly half of those patients who were dispensed an OAT opioid in Norway and Sweden were dispensed potentially addictive drugs. The differences identified between Norway and Sweden might be related to differences in eligibility guidelines and restrictions with respect to OAT.

Shared genetic background between children and adults with attention deficit/hyperactivity disorder.

Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by age-inappropriate symptoms of inattention, impulsivity, and hyperactivity that persist into adulthood in the majority of the diagnosed children. Despite several risk factors during childhood predicting the persistence of ADHD symptoms into adulthood, the genetic architecture underlying the trajectory of ADHD over time is still unclear. We set out to study the contribution of common genetic variants to the risk for ADHD across the lifespan by conducting meta-analyses of genome-wide association studies on persistent ADHD in adults and ADHD in childhood separately and jointly, and by comparing the genetic background between them in a total sample of 17,149 cases and 32,411 controls. Our results show nine new independent loci and support a shared contribution of common genetic variants to ADHD in children and adults. No subgroup heterogeneity was observed among children, while this group consists of future remitting and persistent individuals. We report similar patterns of genetic correlation of ADHD with other ADHD-related datasets and different traits and disorders among adults, children, and when combining both groups. These findings confirm that persistent ADHD in adults is a neurodevelopmental disorder and extend the existing hypothesis of a shared genetic architecture underlying ADHD and different traits to a lifespan perspective.

Correction to: Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): study protocol for a randomized controlled trial.

Following the publication of our article [1], we have become aware of one error in the exclusion criteria, inconsistencies in Figure 1 and Figure 2, and a typo in the reference list.

Dispensation of attention deficit hyperactivity disorder (ADHD) medications in patients receiving opioid agonist therapy; a national prospective cohort study in Norway from 2015 to 2017.

BACKGROUND: It is estimated that up to a third of patients on opioid agonist therapy (OAT) have attention deficit hyperactivity disorder (ADHD). Treatment by ADHD medication, including a centrally acting stimulant (CAS) or atomoxetine is one of the essential approaches. This study evaluates the use of dispensed ADHD medications in the Norwegian OAT population in the period from 2015 to 2017. Types and doses of ADHD medications, co-dispensations of other potentially addictive drugs like benzodiazepines, z-hypnotics, gabapentinoids, and non-OAT opioids, as well as direct-acting antivirals (DAA) against hepatitis C infection, are investigated. METHODS: Information about all dispensed ADHD medication, OAT opioids, and the defined potentially addictive drugs were recorded from the Norwegian Prescription Database. Dispensation rates, the types, and the doses of dispensed ADHD medications were estimated by summarizing the number of dispensations, and the dispensed doses. Logistic regression analyses were employed to assess the associations between ADHD medication, and OAT opioid use, and dispensations of other potentially addictive drugs and DAAs against hepatitis C infection. RESULTS: A total of 9235 OAT patients were included. The proportion of patients who were dispensed ADHD medication increased from 3.5 to 4.6% throughout the study period. The three most dispensed CAS were short- and intermediate-acting methylphenidate (55%), lisdexamphetamine (24%), and dexamphetamine (17%) in 2017. Buprenorphine, rather than methadone, as OAT opioid (adjusted odds ratio: 1.6, CI: 1.2-2.1) was associated with being dispensed ADHD medication. Among patients who received CAS and OAT opioids each calendar year, the dispensed doses of methylphenidate increased from 63 mg/day in 2015 to 76 mg/day in 2017 (p = 0.01). Sixty percent of patients receiving ADHD medications were also dispensed other addictive drugs concomitantly in 2017. Similar results were found in 2015 and 2016. CONCLUSION: Co-prescription of ADHD medications was low among patients on OAT in Norway, considering a high prevalence of ADHD in this patient group. On the other hand, concurrent dispensations of multiple addictive drugs were common in this population. Understanding the underlying reasons for such prescribing is essential, and research on how to optimize ADHD medication of patients with ADHD receiving OAT is needed.

Identification of Genetic Loci Shared Between Attention-Deficit/Hyperactivity Disorder, Intelligence, and Educational Attainment.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown. METHODS: We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes. RESULTS: We identified 58 linkage disequilibrium-independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD. CONCLUSIONS: These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.

Current and Retrospective Childhood Ratings of Emotional Fluctuations in Adults With ADHD.

Introduction: Emotional fluctuations and mood swings are common among adults with Attention Deficit/Hyperactivity Disorder (ADHD). Here we investigated if these problems could be retrospectively traced back to childhood behavior. Methods: Adults with an ADHD diagnosis (n = 502, 48% female) and a population-based control sample (n = 818, 59% female) completed the Adult ADHD Self-report Scale (ASRS), the Wender Utah Rating Scale (WURS) and the Mood Disorder Questionnaire (MDQ). All participants also provided self-reported information about co-existent psychiatric and somatic diseases, and demographic data. Reports on the MDQ were used to define subgroups with [MDQ(+)] and without [MDQ(-)] life-time periods of emotional fluctuations and the WURS scale was used to retrospectively assess childhood ADHD related behaviors and symptoms. Results: 50.2% of the ADHD group and 5% of the controls were defined with emotional fluctuations [MDQ(+)]. Childhood behavior ratings of "impulsivity," "loosing of control," and "trouble with authorities" independently predicted emotional fluctuations reported in adulthood via logistic regression analyses. Inclusion of these three items in a classification analysis gave an accuracy score around 70% in identifying each of the two MDQ categories in the ADHD group. Discussion: The strong association between self-reported features of emotional problems in childhood and in adulthood suggests a trajectory that should be detected and remediated at an early age. Future longitudinal studies should prioritize the examination of developmental mechanisms explaining the persistence of emotional problems from childhood into adulthood.

Cyclothymic temperament: Associations with ADHD, other psychopathology, and medical morbidity in the general population.

BACKGROUND: Cyclothymic temperament (CT) is an affective disposition often preceding bipolar disorder (BD), and is the most common affective temperament in patients with BD. In depressed patients, CT is a predictor for developing a bipolar course. In a clinical sample of adults with BD and attention deficit hyperactivity disorder (ADHD), CT was associated with higher loads of psychiatric symptoms, somatic comorbidity, impairment, and higher morbidity among first-degree relatives. We aimed to investigate the morbidity and occupational functioning of persons with CT in the general population. METHODS: Randomly recruited Norwegian adults (n = 721) were assessed with a 21-item cyclothymic subscale from the TEMPS Autoquestionnaire. Self-reported data were collected on psychiatric symptoms, comorbidity, educational and occupational level, and known family morbidity. RESULTS: Thirteen percent had CT associated with an increased prevalence of ADHD, BD, high scores on the Mood Disorder Questionnaire (MDQ), and childhood and adulthood ADHD symptoms. CT was found in 75% (p < .001) of the bipolar participants, and in 68% (p < .001) of those with a positive MDQ score. CT was associated with more anxiety/depression, substance and alcohol problems, lower educational and occupational levels, and having a first-degree relative with anxiety/depression, alcohol problems, ADHD, and BD. LIMITATIONS: The CT subscale alone might include overlapping features with cyclothymic, anxious, irritable, and depressed temperaments, thus increasing the prevalence estimate of CT. CONCLUSIONS: CT is a strong predictor of occupational failure and associated with more psychiatric impairment in the participants and their families. CT should be assessed in both mood disorder and ADHD patients.

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

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 (rg) 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 (PRADHD, 6.2; 95% confidence interval [CI], 6.1-6.4; PRASD, 1.9; 95% CI, 1.7-2.2; p < .001); however, the opposite was true for schizophrenia (PRASD, 13.9; 95% CI, 12.7-15.2; PRADHD, 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.

Physical exercise augmented cognitive behaviour therapy for older adults with generalised anxiety disorder (PEXACOG): study protocol for a randomized controlled trial.

BACKGROUND: Generalised anxiety disorder (GAD) is a frequent and severe anxiety disorder among older adults. GAD increases the risk of developing other disorders such as depression and coronary heart disease. Older adults with GAD exhibit a poorer response to cognitive behaviour therapy (CBT) compared to younger patients with GAD. The normal age-related cognitive decline can be a contributor to reduced treatment efficacy. One strategy for improving treatment efficacy is to combine CBT with adjunctive interventions targeted at improving cognitive functions. Physical exercise is a viable intervention in this regard. Increased levels of brain-derived neurotrophic factor may mediate improvement in cognitive function. The present study aims to investigate the proposed effects and mechanisms related to concomitant physical exercise. METHODS: The sample comprises 70 participants aged 60-75 years, who have GAD. Exclusion criteria comprise substance abuse and unstable medication; inability to participate in physical exercise; and conditions which precludes GAD as primary diagnosis. The interventions are individual treatment in the outpatient clinic at the local psychiatric hospital, with two experimental arms: (1) CBT + physical exercise and (2) CBT + telephone calls. The primary outcome measure is symptom reduction on the Penn State Worry Questionnaire. Other measures include questionnaires, clinical interviews, physiological, biological and neuropsychological tests. A subset of 40 participants will undergo magnetic resonance imaging (MRI). After inclusion, participants undergo baseline testing, and are subsequently randomized to a treatment condition. Participants attend five sessions of the add-on treatment in the pre-treatment phase, and move on to interim testing. After interim testing, participants attend 10 sessions of CBT in parallel with continued add-on treatment. Participants are tested post-intervention within 2 weeks of completing treatment, with follow-up testing 6 and 12 months later. DISCUSSION: This study aims to develop better treatment for GAD in older adults. Enhancing treatment response will be valuable from both individual and societal perspectives, especially taking the aging of the general population into account. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02690441 . Registered on 24 February 2016.