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1.
Artigo em Inglês | MEDLINE | ID: mdl-31485859

RESUMO

The current study examines whether facial emotion identification and family factors at preadolescence (age 11) predict psychotic experiences 5 years later during adolescence (age 16) and whether family factors may mediate the association between facial emotion identification and psychotic experiences. Data was obtained from the epidemiological cohort TRAILS (N = 2059). At preadolescence, a facial emotion identification test and three questionnaires to assess family functioning, perceived parenting styles and parenting stress, were administered. At adolescence, a questionnaire on psychotic experiences was administered. Facial emotion identification at preadolescence was not associated with psychotic experiences at adolescence, and the mediational role of family functioning was not further explored. However, increased overprotective parenting at preadolescence was associated with a higher frequency of psychotic experiences and delusions at adolescence. Future research may examine the mechanism behind the role of overprotective parenting on psychotic experiences during adolescence.

2.
Int J Methods Psychiatr Res ; : e1795, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31264326

RESUMO

OBJECTIVES: In this study, we examined the consequences of ignoring violations of assumptions underlying the use of sum scores in assessing attention problems (AP) and if psychometrically more refined models improve predictions of relevant outcomes in adulthood. METHODS: Tracking Adolescents' Individual Lives data were used. AP symptom properties were examined using the AP scale of the Child Behavior Checklist at age 11. Consequences of model violations were evaluated in relation to psychopathology, educational attainment, financial status, and ability to form relationships in adulthood. RESULTS: Results showed that symptoms differed with respect to information and difficulty. Moreover, evidence of multidimensionality was found, with two groups of items measuring sluggish cognitive tempo and attention deficit hyperactivity disorder symptoms. Item response theory analyses indicated that a bifactor model fitted these data better than other competing models. In terms of accuracy of predicting functional outcomes, sum scores were robust against violations of assumptions in some situations. Nevertheless, AP scores derived from the bifactor model showed some superiority over sum scores. CONCLUSION: These findings show that more accurate predictions of later-life difficulties can be made if one uses a more suitable psychometric model to assess AP severity in children. This has important implications for research and clinical practice.

3.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31004292

RESUMO

The widely reported association between ADHD and overweight may be attributable to genetic and environmental factors also present in unaffected family members. Therefore, the purpose of this study was to examine the association between ADHD and overweight within families. A cohort was used of families with at least one member with ADHD, recruited as part of the Dutch node of the International Multicenter ADHD Genetics (IMAGE) study, with assessments taking place between 2003 and 2006, 2009 and 2012, and 2013 and 2015. The three assessment waves yielded N = 1828 youth assessments and N = 998 parent assessments from N = 447 unique families. Overweight was defined as a body mass index (BMI) ≥ 85th percentile for youth of the same age and sex; overweight in adults as a BMI ≥ 25. Effects of age, gender, and medication use (psychostimulants, antipsychotics, and melatonin) were taken into account. Generalized estimation equations were used to correct for within-family and within-subject correlations. There was no difference in risk between ADHD-affected youth and their unaffected siblings (OR 0.92, 95% CI 0.78-1.09). However, compared to population prevalence data, all ADHD family members alike were at increased risk for being overweight: ADHD-affected youth (OR 1.33, 95% CI 1.13-1.59), unaffected siblings (OR 1.73, 95% CI 1.45-2.08), mothers (OR 1.74, 95% CI 1.40-2.17) and fathers (OR 1.78, 95% CI 1.46-2.15). Parental overweight-but not parental ADHD-was predictive of offspring overweight (mothers OR 1.40; 95% CI 1.14-1.73, fathers OR 1.83; 95% CI 1.41-2.36). Being overweight runs in ADHD families, yet is not specifically linked to ADHD within families. Shared unhealthy lifestyle factors (including nutrition, sleep, exercise, stress) as well as genetic factors shared by family members likely explain the findings.

5.
Am J Psychiatry ; 176(7): 531-542, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31014101

RESUMO

OBJECTIVE: Neuroimaging studies show structural alterations of various brain regions in children and adults with attention deficit hyperactivity disorder (ADHD), although nonreplications are frequent. The authors sought to identify cortical characteristics related to ADHD using large-scale studies. METHODS: Cortical thickness and surface area (based on the Desikan-Killiany atlas) were compared between case subjects with ADHD (N=2,246) and control subjects (N=1,934) for children, adolescents, and adults separately in ENIGMA-ADHD, a consortium of 36 centers. To assess familial effects on cortical measures, case subjects, unaffected siblings, and control subjects in the NeuroIMAGE study (N=506) were compared. Associations of the attention scale from the Child Behavior Checklist with cortical measures were determined in a pediatric population sample (Generation-R, N=2,707). RESULTS: In the ENIGMA-ADHD sample, lower surface area values were found in children with ADHD, mainly in frontal, cingulate, and temporal regions; the largest significant effect was for total surface area (Cohen's d=-0.21). Fusiform gyrus and temporal pole cortical thickness was also lower in children with ADHD. Neither surface area nor thickness differences were found in the adolescent or adult groups. Familial effects were seen for surface area in several regions. In an overlapping set of regions, surface area, but not thickness, was associated with attention problems in the Generation-R sample. CONCLUSIONS: Subtle differences in cortical surface area are widespread in children but not adolescents and adults with ADHD, confirming involvement of the frontal cortex and highlighting regions deserving further attention. Notably, the alterations behave like endophenotypes in families and are linked to ADHD symptoms in the population, extending evidence that ADHD behaves as a continuous trait in the population. Future longitudinal studies should clarify individual lifespan trajectories that lead to nonsignificant findings in adolescent and adult groups despite the presence of an ADHD diagnosis.

6.
J Am Acad Child Adolesc Psychiatry ; 58(3): 329-338, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30832904

RESUMO

OBJECTIVE: This study investigated whether low reward responsiveness marks vulnerability for developing depression in a large cohort of never-depressed 16-year-old adolescents who completed a reward task and were subsequently followed for 9 years, during which onset of depression was assessed. METHOD: Data were collected as part of the TRacking Adolescents' Individual Lives Survey (TRAILS), an ongoing prospective cohort study. Reward responsiveness was assessed by the spatial orienting task at 16 years and depression was assessed at 19 years by the World Health Organization Composite International Diagnostic Interview and at 25 years by the Lifetime Depression Assessment Self-Report. Participants who completed the reward task at 16 years, had no previous onset of depression, and were assessed on depression onset at 19 and/or 25 years were included in the present study (N = 531; 81 became depressed during follow-up). RESULTS: Difficulties in shifting attention from expected non-reward to expected reward and from expected punishment to expected non-punishment at 16 years predicted depression during follow-up. This was found only at an automatic level of information processing. CONCLUSION: The findings suggest that decreased reward responsiveness at 16 years marks vulnerability for depression. Prevention programs may aim at increasing at-risk adolescents' responsiveness to cues for potential rewards, particularly in situations in which they are focused on negative experiences.

7.
Transl Psychiatry ; 9(1): 114, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30877272

RESUMO

The recent successful genome-wide association studies (GWASs) for depression have yielded more than 80 replicated loci and brought back the excitement that had evaporated during the years of negative GWAS findings. The identified loci provide anchors to explore their relevance for depression, but this comes with new challenges. Using the watershed model of genotype-phenotype relationships as a conceptual aid and recent genetic findings on other complex phenotypes, we discuss why it took so long and identify seven future challenges. The biggest challenge involves the identification of causal mechanisms since GWAS associations merely flag genomic regions without a direct link to underlying biological function. Furthermore, the genetic association with the index phenotype may also be part of a more extensive causal pathway (e.g., from variant to comorbid condition) or be due to indirect influences via intermediate traits located in the causal pathways to the final outcome. This challenge is highly relevant for depression because even its narrow definition of major depressive disorder captures a heterogeneous set of phenotypes which are often measured by even more broadly defined operational definitions consisting of a few questions (minimal phenotyping). Here, Mendelian randomization and future discovery of additional genetic variants for depression and related phenotypes will be of great help. In addition, reduction of phenotypic heterogeneity may also be worthwhile. Other challenges include detecting rare variants, determining the genetic architecture of depression, closing the "heritability gap", and realizing the potential for personalized treatment. Along the way, we identify pertinent open questions that, when addressed, will advance the field.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30721356

RESUMO

Adolescents with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of developing substance use disorders (SUDs) and nicotine dependence (ND). It remains unclear whether and how stimulant treatment may affect this risk. We aimed to investigate how stimulant use profiles influence the risk of SUDs and ND, using a novel data-driven community detection analysis to construct different stimulant use profiles. Comprehensive lifetime stimulant prescription data and data on SUDs and ND were available for 303 subjects with ADHD and 219 controls, with a mean age 16.3 years. Community detection was used to define subgroups based on multiple indicators of treatment history, start age, treatment duration, total dose, maximum dose, variability, stop age. In stimulant-treated participants, three subgroups with distinct medication trajectories were distinguished (late-and-moderately dosed, n = 91; early-and-moderately dosed, n = 51; early-and-intensely dosed, n = 103). Compared to stimulant-naïve participants (n = 58), the early-and-intense treatment group had a significantly lower risk of SUDs and ND (HR = 0.28, and HR = 0.29, respectively), while the early-and-moderate group had a significantly lower risk of ND only (HR = 0.30). The late-and-moderate group was at a significantly higher risk of ND compared to the other two treatment groups (HR = 2.66 for early-and-moderate, HR = 2.78 for early-and-intense). Our findings show that in stimulant-treated adolescents with ADHD, long-term outcomes are associated with treatment characteristics, something that is often ignored when treated individuals are compared to untreated individuals.

9.
Eur Psychiatry ; 58: 38-44, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30802682

RESUMO

BACKGROUND: ADHD is a highly prevalent disease in childhood which often persists into adulthood, then co-occurring with common adult conditions. Especially for adult ADHD, little is known about the costs of ADHD and the additional costs of comorbid conditions. AIMS: To determine medical costs of ADHD and costs of comorbidities (mood, anxiety and substance use disorders, obesity), including their co-occurrence rates, stratified by age and gender. METHOD: Claims data from a German Statutory Health Insurance database with approximately four million member-records per year were analysed. A total of 25,300 prevalent ADHD patients were identified by means of an ICD-10 GM diagnosis of ADHD. A 1:1 age and gender adjusted reference group without ADHD diagnosis was randomly selected. Total health claims and health care costs related to ADHD were analysed, in addition to more targeted analyses of the occurrence and costs of pre-defined common comorbidities of, in particular, adult ADHD (SUD, mood and anxiety disorders, obesity). Outcomes were mean costs per patient and occurrence rates of comorbid conditions. Surplus costs of a comorbid condition in persons with ADHD relative to costs of this condition in persons without ADHD were calculated. Subgroup analyses were conducted based on age (0-12 years, 13-17 years, 18-30years, 30+ years) and gender. RESULTS: Patients with ADHD were €1500 more expensive annually than individuals without ADHD (p < 0.001). Main cost drivers were inpatient care, psychiatrists and psychotherapists. Mood, anxiety, substance use disorders and obesity were significantly more frequent in ADHD patients and additional costs resulting from the comorbid conditions amounted up to €2800. Costs were slightly higher in women than men and increased with age for both genders. In young adults (18-30 years) health care costs dropped notably, especially costs for the medical treatment of ADHD with stimulants and costs for psychiatrists, before rising again in the group of patients over 30 years who had higher comorbidity rates. CONCLUSIONS: Medical costs for ADHD are substantial, in part through frequently occurring comorbid conditions, and particularly in adulthood, and are likely to further accelerate in the coming years. A gap of care was found, starting with the transition age group of patients over 17 years, as indicated by reduced costs per person during young adulthood, as well as an overall strong drop in administrative prevalence. In the future, approaches to improve the situation of care and reduce costs at the same time, i.e. through managed care programmes, should be implemented and benefit from detailed knowledge on age and gender-specific cost-drivers.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/economia , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Doença Crônica/economia , Doença Crônica/epidemiologia , Comorbidade , Análise de Dados , Feminino , Alemanha , Serviços de Saúde/economia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Saúde Pública/economia , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-30773473

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, putatively induced by dissociable dysfunctional biobehavioral pathways. Here, we present a proof-of-concept study to parse ADHD-related heterogeneity in its underlying neurobiology by investigating functional connectivity across multiple brain networks to 1) disentangle categorical diagnosis-related effects from dimensional behavior-related effects and 2) functionally map these neural correlates to neurocognitive measures. METHODS: We identified functional connectivity abnormalities related to ADHD across 14 networks within a large resting-state functional magnetic resonance imaging dataset (n = 409; age = 17.5 ± 3.3 years). We tested these abnormalities for their association with the categorical ADHD diagnosis and with dimensional inattention and hyperactivity/impulsivity scores using a novel modeling framework, creating orthogonalized models. Next, we evaluated the relationship of these findings with neurocognitive measures (working memory, response inhibition, reaction time variability, reward sensitivity). RESULTS: Within the default mode network, we mainly observed categorical ADHD-related functional connectivity abnormalities, unrelated to neurocognitive measures. Clusters within the visual networks primarily related to dimensional scores of inattention and reaction time variability, while findings within the sensorimotor networks were mainly linked to hyperactivity/impulsivity and both reward sensitivity and working memory. Findings within the cerebellum network and salience network related to both categorical and dimensional ADHD measures and were linked to response inhibition and reaction time variability. CONCLUSIONS: This proof-of-concept study identified ADHD-related neural correlates across multiple functional networks, showing distinct categorical and dimensional mechanisms and their links to neurocognitive functioning.

11.
Mol Psychiatry ; 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30626913

RESUMO

Although a genetic basis of depression has been well established in twin studies, identification of genome-wide significant loci has been difficult. We hypothesized that bivariate analyses of findings from a meta-analysis of genome-wide association studies (meta-GWASs) of the broad depression phenotype with those from meta-GWASs of self-reported and recurrent major depressive disorder (MDD), bipolar disorder and schizophrenia would enhance statistical power to identify novel genetic loci for depression. LD score regression analyses were first used to estimate the genetic correlations of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia. Then, we performed four bivariate GWAS analyses. The genetic correlations (rg ± SE) of broad depression with self-reported MDD, recurrent MDD, bipolar disorder and schizophrenia were 0.79 ± 0.07, 0.24 ± 0.08, 0.53 ± 0.09 and 0.57 ± 0.05, respectively. From a total of 20 independent genome-wide significant loci, 13 loci replicated of which 8 were novel for depression. These were MUC21 for the broad depression phenotype with self-reported MDD and ZNF804A, MIR3143, PSORS1C2, STK19, SPATA31D1, RTN1 and TCF4 for the broad depression phenotype with schizophrenia. Post-GWAS functional analyses of these loci revealed their potential biological involvement in psychiatric disorders. Our results emphasize the genetic similarities among different psychiatric disorders and indicate that cross-disorder analyses may be the best way forward to accelerate gene finding for depression, or psychiatric disorders in general.

12.
J Neurodev Disord ; 10(1): 42, 2018 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-30587104

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with substance use disorders (SUD; alcohol and/or drug dependence) and nicotine dependence. This study aims to advance our knowledge about the association between SUD, nicotine dependence, and the course of ADHD (persistent versus remittent ADHD and late-onset ADHD). METHODS: ADHD, SUD, and nicotine dependence were longitudinally assessed (mean age at study entry 11.3 years, mean age at follow-up 21.1 years) using structured psychiatric interviews and multi-informant questionnaires in a subsample of the Dutch part of the International Multicenter ADHD Genetics study. Individuals with persistent ADHD (n = 62), remittent ADHD (n = 12), late-onset ADHD (n = 18; age of onset after 12 years), unaffected siblings (n = 50), and healthy controls (n = 47) were assessed. Hazard ratios (HR) with 95% confidence intervals (CIs) were estimated by Cox regression and adjusted for clustered family data, gender, follow-up length, and current age. RESULTS: Individuals with persistent ADHD were at significantly higher risk of development of SUD relative to healthy controls (HR = 4.56, CI 1.17-17.81). In contrast, levels of SUD in those with remittent ADHD were not different from healthy controls (HR = 1.00, CI .07-13.02). ADHD persisters had also higher prevalence rates of nicotine dependence (24.2%) than ADHD remitters (16.7%) and healthy controls (4.3%). A similar pattern was found in initially unaffected siblings who met ADHD criteria at follow-up ("late-onset" ADHD); they had also a higher prevalence of SUD (33%) compared to stable unaffected siblings (20%) and were at significantly increased risk of development of nicotine dependence compared to healthy controls (HR = 13.04, CI 2.08-81.83). CONCLUSIONS: SUD and nicotine dependence are associated with a negative ADHD outcome. Results further emphasize the need for clinicians to comprehensively assess substance use when diagnosing ADHD in adolescents and adults.

13.
Mol Psychiatry ; 2018 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-30279459

RESUMO

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

14.
Psychol Med ; : 1-9, 2018 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-30220266

RESUMO

BACKGROUND: A recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity. METHOD: By linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis. RESULTS: Individuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55-3.90%; risk ratio 3.05, 95% CI 2.95-3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (rg 0.30, 95% CI 0.17-0.44). CONCLUSION: The association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory.

15.
Front Psychol ; 9: 1663, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233475

RESUMO

Clinical reports suggest that children with autism spectrum disorder (ASD) struggle with time perception, but few studies have investigated this. This is the first study to examine these children's understanding of before and after. These temporal conjunctions have been argued to require additional cognitive effort when conjoining two events in a clause order that is incongruent with their order in time. Given the suggested time perception impairment and well-established cognitive deficits of children with ASD, we expected them to have difficulties interpreting temporal conjunctions, especially in an incongruent order. To investigate this, the interpretation of before and after in congruent and incongruent orders was examined in 48 children with ASD and 43 typically developing (TD) children (age 6-12). Additional tasks were administered to measure Theory of Mind (ToM), working memory (WM), cognitive inhibition, cognitive flexibility, IQ, and verbal ability. We found that children with ASD were less accurate in their interpretation of temporal conjunctions than their TD peers. Contrary to our expectations, they did not have particular difficulties in an incongruent order. Furthermore, older children showed better overall performance than younger children. The difference between children with ASD and TD children was explained by WM, ToM, IQ, and verbal ability, but not by cognitive inhibition and flexibility. These cognitive functions are more likely to be impaired in children with ASD than in TD children, which could account for their poorer performance. Thus, the cognitive factors found to affect the interpretation of temporal language in children with ASD are likely to apply in typical development as well. Sufficient WM capacity and verbal ability may help children to process complex sentences conjoined by a temporal conjunction. Additionally, ToM understanding was found to be related to children's interpretation of temporal conjunctions in an incongruent order, indicating that perspective taking is required when events are presented out of order. We conclude from this that perspective-taking abilities are needed for the interpretation of temporal conjunctions, either to shift one's own perspective as a hearer to another point in time, or to shift to the perspective of the speaker to consider the speaker's linguistic choices.

16.
PLoS One ; 13(9): e0204516, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30256837

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is often comorbid with other psychiatric conditions in adults. Yet, less is known about its relationship with common metabolic disorders and how sex and ageing affect the overall comorbidity patterns of adult ADHD. We aimed to examine associations of adult ADHD with several common psychiatric and metabolic conditions. Through the linkage of multiple Swedish national registers, 5,551,807 adults aged 18 to 64 years and living in Sweden on December 31, 2013 were identified and assessed for clinical diagnoses of adult ADHD, substance use disorder (SUD), depression, bipolar disorder, anxiety, type 2 diabetes mellitus (T2DM), and hypertension. Logistic regression models and regression standardization method were employed to obtain estimates of prevalence, prevalence difference (PD), and prevalence ratio (PR). All comorbid conditions of interest were more prevalent in adults with ADHD (3.90% to 44.65%) than in those without (0.72% to 4.89%), with the estimated PRs being over nine for psychiatric conditions (p < 0.001) and around two for metabolic conditions (p < 0.001). Sex differences in the prevalence of comorbidities were observed among adults with ADHD. Effect modification by sex was detected on the additive scale and/or multiplicative scale for the associations of adult ADHD with all comorbidities. ADHD remained associated with all comorbidities in older adults aged 50 to 64 when all conditions were assessed from age 50 onwards. The comorbidity patterns of adult ADHD underscore the severity and clinical complexity of the disorder. Clinicians should remain vigilant for a wide range of psychiatric and metabolic problems in ADHD affected adults of all ages and both sexes.

17.
Nat Neurosci ; 21(9): 1161-1170, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150663

RESUMO

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

18.
Addiction ; 113(11): 2073-2086, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003630

RESUMO

BACKGROUND AND AIMS: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. METHODS: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. RESULTS: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19-60%]. Shared and unique environmental factors explained 39% (95% CI = 20-56%) and 22% (95% CI = 16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P < 5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2  > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. CONCLUSION: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.

19.
J Abnorm Psychol ; 127(2): 228-238, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29528676

RESUMO

Pronoun reversals, saying you when meaning I, in children with autism spectrum disorder (ASD) are generally viewed as manifesting in early development and speech production only. This study investigates pronoun reversals in later development (age 6-12) in interpretation in 48 Dutch-speaking children with ASD and 43 typically developing (TD) peers. We contrasted children's interpretation of I and you in indirect and direct speech reports, with the latter type requiring an additional perspective shift. To examine which cognitive processes are involved in pronoun interpretation, additional tasks were administered to measure Theory of Mind (ToM) understanding, cognitive inhibition, cognitive flexibility, and working memory. We found that children with ASD showed more problems than TD children interpreting pronouns in direct speech, resulting in pronoun reversals in interpretation. Children with ASD hardly improved with age. Older children with ASD thus showed more pronoun reversals than did their TD peers. ToM understanding, working memory, IQ, and verbal ability, but not inhibition and flexibility, were associated with pronoun interpretation. ToM understanding in particular was associated with correct pronoun interpretation in older TD children relative to younger TD children, but this improvement was not found in children with ASD. These findings indicate that pronoun reversals most likely result from perspective-shifting difficulties. We conclude that pronoun reversals are more pronounced in individuals with ASD, occur beyond early development, and require sufficient cognitive resources. The relation with ToM understanding, but not inhibition and flexibility, suggests that pronoun reversals are best classified as a social communication problem in the diagnosis of ASD. (PsycINFO Database Record

20.
J Child Psychol Psychiatry ; 59(7): 763-772, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29520926

RESUMO

BACKGROUND: Several delivery formats of cognitive behaviour therapy (CBT) for child anxiety have been proposed, however, there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child's primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT and guided parent-led CBT. The secondary goal was to investigate the impact of the child's primary anxiety diagnosis on rates of remission for the three treatment formats. METHODS: A sample of 1,253 children (5-12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of generalised anxiety disorder (GAD), social anxiety disorder (SoAD), specific phobia (SP) or separation anxiety disorder (SAD). Children and parents completed a semistructured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at preintervention, postintervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question. RESULTS: In children with primary GAD, SAD or SoAD, there were no significant differences between delivery formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. The difference between individual and group was not significant when follow-up data were examined separately. CONCLUSIONS: Data show there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required.

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