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1.
Artigo em Inglês | MEDLINE | ID: mdl-33059383

RESUMO

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

2.
Transl Psychiatry ; 10(1): 328, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968041

RESUMO

The U.S. National Institute of Mental Health (NIMH) introduced the research domain criteria (RDoC) initiative to promote the integration of information across multiple units of analysis (i.e., brain circuits, physiology, behavior, self-reports) to better understand the basic dimensions of behavior and cognitive functioning underlying normal and abnormal mental conditions. Along those lines, this study examined the association between peripheral blood gene expression levels and emotional and behavioral problems in school-age children. Children were chosen from two age- and sex-matched groups: those with or without parental reports of any prior or current psychiatric diagnosis. RNA-sequencing was performed on whole blood from 96 probands aged 6-12 years who were medication-free at the time of assessment. Module eigengenes were derived using weighted gene co-expression network analysis (WGCNA). Associations were tested between module eigengene expression levels and eight syndrome scales from parent ratings on the Child Behavior Checklist (CBCL). Nine out of the 36 modules were significantly associated with at least one syndrome scale measured by the CBCL (i.e., aggression, social problems, attention problems, and/or thought problems) after accounting for covariates and correcting for multiple testing. Our study demonstrates that variation in peripheral blood gene expression relates to emotional and behavioral profiles in children. If replicated and validated, our results may help in identifying problem or at-risk behavior in pediatric populations, and in elucidating the biological pathways that modulate complex human behavior.

4.
J Atten Disord ; : 1087054720943283, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697138

RESUMO

Objective: The purpose of the present study was to characterize prescription stimulant non-medical use (NMU) in adolescents between the ages of 13 and 18 years seeking treatment for substance use disorder (SUD) with the Comprehensive Health Assessment Tool for Teens (CHAT™). Method: Adolescents being evaluated for SUD treatment between Q1 2010 and Q3 2017 (n = 20,189) completed the CHAT™. Results: About 4.3% of the sample (N = 867) of adolescents in SUD treatment reported past 30-day prescription stimulant NMU. Compared to those without past 30-day prescription stimulant NMU, more reported a lifetime diagnosis of learning disorder or ADHD, more took medication for emotional, behavioral, or learning disorders, received past-month inpatient treatment, or were currently not enrolled in school. Prescription stimulants were most often taken orally for NMU, however, approximately half reported using alternate routes of administration, the most prominent of which was intranasal use. Conclusion: About 4.3% of adolescents in SUD treatment evaluation reported past 30-day prescription stimulant NMU. Greater percentages of lifetime learning disorder, medication use, past-month inpatient treatment, school unenrollment, and overall substance misuse were associated with prescription stimulant NMU, as were alternate routes of administration. These data reveal an ongoing, persistent level of past-30-day NMU of prescription stimulants among adolescents being evaluated for SUD treatment.

5.
Eur Addict Res ; 26(4-5): 223-232, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32634814

RESUMO

BACKGROUND: Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. OBJECTIVE: The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. METHOD: A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. RESULTS: After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (n = 4), risk of developing SUD (n = 3), screening and diagnosis (n = 7), psychosocial treatment (n = 5), pharmacological treatment (n = 11), and complementary treatments (n = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. CONCLUSION: This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.

6.
Transl Psychiatry ; 10(1): 182, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32518222

RESUMO

Many psychiatric disorders are associated with impaired executive functioning (EF). The associated EF component varies by psychiatric disorders, and this variation might be due to genetic liability. We explored the genetic association between five psychiatric disorders and EF in clinically-recruited attention deficit hyperactivity disorder (ADHD) children using polygenic risk score (PRS) methodology. Genome-wide association study (GWAS) summary data for ADHD, major depressive disorder (MDD), schizophrenia (SZ), bipolar disorder (BIP) and autism were used to calculate the PRSs. EF was evaluated by the Stroop test for inhibitory control, the trail-making test for cognitive flexibility, and the digital span test for working memory in a Chinese ADHD cohort (n = 1147). Exploratory factor analysis of the three measures identified one principal component for EF (EF-PC). Linear regression models were used to analyze the association between each PRS and the EF measures. The role of EF measures in mediating the effects of the PRSs on ADHD symptoms was also analyzed. The result showed the PRSs for MDD, ADHD and BIP were all significantly associated with the EF-PC. For each EF component, the association results were different for the PRSs of the five psychiatric disorders: the PRSs for ADHD and MDD were associated with inhibitory control (adjusted P = 0.0183 and 0.0313, respectively), the PRS for BIP was associated with working memory (adjusted P = 0.0416), and the PRS for SZ was associated with cognitive flexibility (adjusted P = 0.0335). All three EF measures were significantly correlated with ADHD symptoms. In mediation analyses, the ADHD and MDD PRSs, which were associated with inhibitory control, had significant indirect effects on ADHD symptoms through the mediation of inhibitory control. These findings indicate that the polygenic risks for several psychiatric disorders influence specific executive dysfunction in children with ADHD. The results helped to clarify the relationship between risk genes of each mental disorder and the intermediate cognitive domain, which may further help elucidate the risk genes and motivate efforts to develop EF measures as a diagnostic marker and future treatment target.

7.
J Clin Psychopharmacol ; 40(4): 350-358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32590405

RESUMO

PURPOSE/BACKGROUND: HLD200 is an evening-dosed, delayed-release and extended-release methylphenidate (DR/ER-MPH) that provides a consistent delay in initial drug release to target onset of therapeutic effect from awakening and maintain it into the evening. Building on a modeling framework established with other extended-release methylphenidate formulations, pharmacokinetic (PK) and PK/pharmacodynamic (PD) models for DR/ER-MPH were developed to describe the time course of effect in response to a range of doses and administration times. METHODS/PROCEDURES: Using available PK data from healthy adults, a population PK model was developed using a 1-compartment model with a time-varying absorption rate described by a single Weibull function. A PK/PD model was then developed using Swanson, Kotkin, Agler, M-Flynn, and Pelham combined scores from a phase 3 trial of children with attention-deficit/hyperactivity disorder and simulated plasma concentration-time data. Simulations using the PK/PD model were performed for doses of 60, 80, and 100 mg of DR/ER-MPH, administered 4 to 14 hours before the classroom day. FINDINGS/RESULTS: The PK/PD model predicts that DR/ER-MPH produces a clinical response from early morning into the late afternoon or evening, with increased duration of response occurring with increasing doses. Furthermore, the PK/PD model predicts that maximal clinical effect is achieved with DR/ER-MPH administered 12 hours before the start of the classroom day. IMPLICATIONS/CONCLUSIONS: Model-predicted duration of benefit with DR/ER-MPH is consistent with trial data documenting improvements in functional impairment during the early morning and evening. This model may facilitate dosage optimization by predicting changes in clinical benefit with dose and administration time adjustment.

8.
Psychiatry Res ; 291: 113158, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32559669

RESUMO

AIMS: We piloted the effectiveness and acceptability of a novel text messaging-based (SMS) digital health intervention aimed at addressing the previously documented poor rate of patient engagement in stimulant treatment in the primary care setting. METHODS: 117 adults ages 18-55 from primary care and psychiatric practices who were prescribed a stimulant medication for ADHD treatment received the SMS intervention. Comparators were age-, race-, and sex-matched patients from the same health care organization's electronic medical record who had been prescribed stimulant medications over a similar time period. Using documented prescription records, we determined whether patients had timely prescription refills. RESULTS: Ninety-six percent (N = 112) of participants completed our a priori metric of patient engagement consisting of 37 days of the SMS program. Eighty-one percent of participants refilled their index prescriptions in a timely manner compared to only 36% of patients receiving treatment as usual (OR=7.54, 95% CI: 4.46, 12.77; p<0.001). We found no significant interaction between prescribing source (non-psychiatry vs. psychiatry) and intervention group (SMS vs. treatment as usual). CONCLUSIONS: These data suggest that an ADHD-centric, digital health intervention using text messaging significantly improves patient engagement in stimulant treatment in adults with ADHD.

9.
Psychopharmacology (Berl) ; 237(9): 2835-2843, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32591937

RESUMO

RATIONALE: ADHD is a prevalent and morbid neurobiological disorder affecting up to 5% of adults. While stimulants have been documented to be safe and effective in adults with ADHD, uncertainties remain about adherence to these treatments. OBJECTIVES: The main aim of this article was to evaluate contemporaneous rates and correlates of adherence to stimulants in adults with ADHD using data from electronic medical records from a large healthcare organization focusing on timely renewal of an initial prescription. METHODS: Subjects were patients 18 to 44 years of age who had been prescribed a stimulant between January 1, 2015, and December 31, 2016. Prescription and sociodemographic data were extracted from the Partners HealthCare Research Patient Data Registry (RPDR). Our outcome metric was renewal of the index stimulant prescription defined as the first prescription recorded in the electronic record for the period under investigation. RESULTS: We identified 2689 patients with an index prescription for a stimulant medication. Results showed that only 42% of patients renewed their prescriptions in a timely enough fashion to be considered consistently medicated. CONCLUSIONS: Results indicate that adults with ADHD have a low rate of renewal of their initial stimulant prescription indicating poor patient engagement in their treatment for ADHD.

10.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32561156

RESUMO

OBJECTIVE: This study aims to assess the validity of the ADHD module of the Mini-International Neuropsychiatric Interview (MINI-Plus) in patients with substance use disorders (SUD), using the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) as the external criterion. METHOD: A cross sectional international multi-center study in 10 countries was conducted in treatment seeking SUD patients. A sample of 1263 patients with both MINI-Plus and CAADID was analyzed to determine the psychometric properties of the MINI-Plus. RESULTS: According to the CAADID, 179 patients (14.2%) met criteria for adult ADHD, whereas according to the MINI-Plus 227 patients (18.0%) were identified as having adult ADHD. Sensitivity of the MINI-Plus ADHD module was 74%, specificity was 91%, positive predictive value was 60% and negative predictive value was 96%. Kappa was 0.60. CONCLUSION: The MINI-Plus has acceptable criterion validity for the screening of adult ADHD in treatment seeking SUD patients. SCIENTIFIC SIGNIFICANCE: On the basis of the results, The MINI-Plus may be used for the screening of ADHD in SUD patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-32400953

RESUMO

Variations in SLC9A9 gene expression and protein function are associated with multiple human diseases, which range from Attention-deficit/hyperactivity disorder (ADHD) to glioblastoma multiforme. In an effort to determine the full spectrum of human disease associations with SLC9A9, we performed a systematic review of the literature. We also review SLC9A9's biochemistry, protein structure, and function, as well as its interacting partners with the goal of identifying mechanisms of disease and druggable targets. We report gaps in the literature regarding the genes function along with consistent trends in disease associations that can be used to further research into treating the respective diseases. We report that SLC9A9 has strong associations with neuropsychiatric diseases and various cancers. Interestingly, we find strong overlap in SLC9A9 disease associations and propose a novel role for SLC9A9 in neuropsychiatric comorbidity. In conclusion, SLC9A9 is a multifunctional protein that, through both its endosome regulatory function and its protein-protein interaction network, has the ability to modulate signaling axes, such as the PI3K pathway, among others.

12.
Sci Rep ; 10(1): 8622, 2020 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451437

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is an impairing neurodevelopmental condition highly prevalent in current populations. Several hypotheses have been proposed to explain this paradox, mainly in the context of the Paleolithic versus Neolithic cultural shift but especially within the framework of the mismatch theory. This theory elaborates on how a particular trait once favoured in an ancient environment might become maladaptive upon environmental changes. However, given the lack of genomic data available for ADHD, these theories have not been empirically tested. We took advantage of the largest GWAS meta-analysis available for this disorder consisting of over 20,000 individuals diagnosed with ADHD and 35,000 controls, to assess the evolution of ADHD-associated alleles in European populations using archaic, ancient and modern human samples. We also included Approximate Bayesian computation coupled with deep learning analyses and singleton density scores to detect human adaptation. Our analyses indicate that ADHD-associated alleles are enriched in loss of function intolerant genes, supporting the role of selective pressures in this early-onset phenotype. Furthermore, we observed that the frequency of variants associated with ADHD has steadily decreased since Paleolithic times, particularly in Paleolithic European populations compared to samples from the Neolithic Fertile Crescent. We demonstrate this trend cannot be explained by African admixture nor Neanderthal introgression, since introgressed Neanderthal alleles are enriched in ADHD risk variants. All analyses performed support the presence of long-standing selective pressures acting against ADHD-associated alleles until recent times. Overall, our results are compatible with the mismatch theory for ADHD but suggest a much older time frame for the evolution of ADHD-associated alleles compared to previous hypotheses.

13.
Psychiatry Res ; 289: 113021, 2020 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-32447091

RESUMO

The Research Domain Criteria (RDoC) initiative of the National Institute of Mental Health (NIMH) established a dimensional framework for understanding psychiatric constructs. Initial Responsiveness to Reward Attainment (IRRA) was identified as a dimensional construct relevant to several psychiatric disorders. The current study aimed to (1) examine IRRA as a predictor of psychopathology and impairment in children and their parents, and (2) examine the potential effects of sex and ancestry on the relationship between IRRA and psychopathology. Participants included 1127 children ages 6 to 12, and 1018 of their parents. Parents and children completed self-report measures of IRRA. Psychopathology and impairment were measured using self-report for adults, and parent-report and semi-structured interview for children. In adults, IRRA was significantly, but modestly, related to adaptive functioning. In children, IRRA was significantly, but modestly, related to overall, school, spare time, home, and peer functioning. Findings suggest IRRA may be a helpful construct for understanding adaptive functioning in adults and children, however it may be less helpful for understanding specific dimensions of psychopathology. Additionally, ancestry should be taken into consideration when examining how IRRA relates to psychopathology and functioning.

14.
Neuropsychopharmacology ; 45(10): 1617-1626, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32279069

RESUMO

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.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32246275

RESUMO

BACKGROUND: Consistent research findings indicate that parents and teachers observe genuinely different Attention Deficit/Hyperactivity Disorder (ADHD) behaviours in their respective settings. OBJECTIVE: To evaluate the utility of information provided by teacher informant assessments (INFAs) of ADHD symptoms, and the implications of aggregation algorithms in combing parents' information, i.e. using 'or-rule' (endorsement by either one informant) versus 'and-rule' (endorsement by both informants). METHOD: Teacher ratings on Conners scales and clinical data from parental accounts on 1383 probands and their siblings from the IMAGE study were analysed. The psychometric properties of teacher and combined ratings using the item response theory model (IRT) are presented. Kappa coefficients, intraclass correlations and linear regression were employed. RESULTS: First, teacher endorsement of symptoms is located in a narrow part of the trait continuum close to the average levels. Symptoms exhibit comparable perception in the measurement of the trait(s) with similar discrimination ability and information (reliability). Second, the IRT properties of the 'or-rule' ratings are predominantly influenced by parent-INFAs; and the 'and-rule' ratings predominantly by teacher-INFAs ratings. Third, parent-teacher INFAs agreement was low, both for individual items (κ = 0.01-0.15) and for dimensional scores (r = 0.12-0.16). The 'or-rule' captured milder expressions of ADHD symptoms, whereas the 'and-rule' indexed greater severity of ADHD. CONCLUSIONS: Parent and teacher-INFAs provide different kinds of information, while both are useful. Teacher-INFA and the 'and-rule' provide a more accurate index of severity than an additive symptom count. Parent-INFA and the 'or-rule' are more sensitive for detecting cases with milder ADHD.

16.
Artigo em Inglês | MEDLINE | ID: mdl-32237208

RESUMO

AIM: The peak onset of psychotic disorders occurs during adolescence and early adulthood, yet treatments for youth at clinical high risk (CHR) for psychosis are generally designed for adults. CHR youth, despite poor academic and social engagement, spend hours each day playing complicated videogames. The aim of this study was to test the feasibility of integrating biofeedback and cooperative videogame play within family therapy as a means of engaging and enhancing this population's resilience. METHODS: We conducted a feasibility trial of an innovative 12-week family therapy for CHR ages 12-30 (clinicaltrials.gov NCT02531243). We report feasibility outcomes and preliminary effect sizes for pre-post changes and youth-parent differences. RESULTS: Of 88 individuals referred to the centre who met age and CHR criteria, 11 (13%) youth-parent pairs met full criteria and engaged in treatment. Ten (91%) completed at least six sessions. Youth found CALMS initially credible, but parents tended to find it more credible and to be more satisfied over time. Surprisingly, parents reported a better game experience than youth. As a group, youth and parent participants reported experiencing reduced stress and perceiving each other as less critical by the end of treatment. Youth were rated as having significantly improved social, but not role or global functioning by the end of treatment. CONCLUSIONS: Multiuser videogames may have a role to play in engaging youth at risk for psychosis in therapy and reducing stress and familial risk factors. A number of key developments are needed to enhance the appeal, effectiveness and practicality of this approach.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32237241

RESUMO

BACKGROUND: Children with attention-deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at-risk youth would help allocate scarce resources for prevention programs. METHODS: Psychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress, and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989 and 1993. We trained (a) a cross-sectional random forest (RF) model using data available by age 17 to predict SUD diagnosis between ages 18 and 19; and (b) a longitudinal recurrent neural network (RNN) model with the Long Short-Term Memory (LSTM) architecture to predict new diagnoses at each age. RESULTS: The area under the receiver operating characteristic curve (AUC) was 0.73(95%CI 0.70-0.76) for the random forest model (RF). Removing prior diagnosis from the predictors, the RF model was still able to achieve significant AUCs when predicting all SUD diagnoses (0.69, 95%CI 0.66-0.72) or new diagnoses (0.67, 95%CI: 0.64, 0.71) during age 18-19. For the model predicting new diagnoses, model calibration was good with a low Brier score of 0.086. Longitudinal LSTM model was able to predict later SUD risks at as early as 2 years age, 10 years before the earliest diagnosis. The average AUC from longitudinal models predicting new diagnoses 1, 2, 5 and 10 years in the future was 0.63. CONCLUSIONS: Population registry data can be used to predict at-risk comorbid SUDs in individuals with ADHD. Such predictions can be made many years prior to age of the onset, and their SUD risks can be monitored using longitudinal models over years during child development. Nevertheless, more work is needed to create prediction models based on electronic health records or linked population registers that are sufficiently accurate for use in the clinic.

18.
Transl Psychiatry ; 10(1): 100, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198361

RESUMO

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.

19.
Child Psychiatry Hum Dev ; 51(6): 978-985, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32172405

RESUMO

This study investigated the diagnostic utility of the Child Behavior Checklist (CBCL) Rule-Breaking Behavior scale to identify children of both sexes with conduct disorder (CD). Participants were derived from four independent datasets of children with and without attention deficit hyperactivity disorder and bipolar-I disorder of both sexes. Participants had structured diagnostic interviews with raters blinded to subject ascertainment status. Receiver operating characteristic (ROC) curves were used to examine the scale's ability to identify children with and without CD. The sample consisted of 674 participants (mean age of 11.7 ± 3.3 years, 57% male, 94% Caucasian). The interaction to test if CBCL Rule-Breaking Behavior scores identified males and females with CD differently was not significant, thus we performed ROC analysis in the combined group. The ROC analysis of the scale yielded an area under the curve of 0.9. A score of ≥ 60 on the scale correctly classified 82% of participants with CD with 85% sensitivity, 81% specificity, 48% positive predictive value, 96% negative predictive value. The CBCL Rule-Breaking Behavior scale was an efficient tool to identify children with CD.

20.
Transl Psychiatry ; 10(1): 70, 2020 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-32075956

RESUMO

The identification of biomarkers to support the diagnosis and prediction of treatment response for attention-deficit/hyperactivity disorder (ADHD) is still a challenge. Our previous works highlighted the DRD4 (dopamine receptor D4) as the best potential genetic marker for childhood diagnosis and methylphenidate (MPH) response. Here, we aimed to provide additional evidence on biomarkers for ADHD diagnosis and treatment response, by using more specific approaches such as meta-analytic and bioinformatics tools. Via meta-analytic approaches including over 3000 cases and 16,000 controls, we demonstrated that, among the different variants studied in DRD4 gene, the 48-base pair, Variable Tandem Repeat Polymorphism, VNTR in exon 3 showed an age/population-specificity and an allelic heterogeneity. In particular, the 7R/"long" allele was identified as an ADHD risk factor in European-Caucasian populations (d = 1.31, 95%CI: 1.17-1.47, Z = 4.70/d = 1.36, 95%CI: 1.20-1.55, Z = 4.78, respectively), also, from the results of last meta-analysis, linked to the poor MPH efficacy. The 4R/"short" allele was a protective factor in European-Caucasian and South American populations (d = 0.83, 95%CI: 0.75-0.92, Z = 3.58), and was also associated to positive MPH response. These results refer to children with ADHD. No evidence of such associations was detected for adults with persistent ADHD (data from the last meta-analysis). Moreover, we found evidence that the 4R allele leads to higher receptor expression and increased sensitivity to dopamine, as compared with the 7R allele (d = 1.20, 95%CI: 0.71-1.69, Z = 4.81), and this is consistent with the ADHD protection/susceptibility effects of the respective alleles. Using bioinformatics tools, based on the latest genome-wide association (GWAS) meta-analysis of the Psychiatry Genomic Consortium (PGC), we demonstrated that the 48 bp VNTR is not in Linkage Disequilibrium with the DRD4 SNPs (Single Nucleotide Polymorphisms), which were not found to be associated with ADHD. Moreover, a DRD4 expression downregulation was found in ADHD specific brain regions (Putamen, Z score = -3.02, P = 0.00252). Overall, our results suggest that DRD4 48 bp VNTR variants should be considered as biomarkers to support the diagnosis of ADHD and to predict MPH response, although the accuracy of such a biomarker remains to be further elucidated.

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