Perfiles psicosociales de adultos con TDAH: un estudio comparativo con muestras reclusa y clínica

ADHD; Prison; Outpatient psychiatric patients; Legal consequencesTDAH; Carcelarios; Muestra clínica; Consecuencias legalesTDAH; Presó; Pacients psiquiàtrics ambulatoris; Conseqüències legalsThis study aimed to describe and compare the educational, social, and family profiles of adults with and without ADHD from two different settings: a prison and an outpatient psychiatric setting. A total of 542 participants, aged between 17 and 69 years, took part in the study. The participants consisted of four groups: a prison sample with ADHD (n = 69) and without ADHD (n = 183), and an outpatient psychiatric sample with ADHD (n = 218) and without ADHD (n = 72). The results showed that, firstly, there were some statistically significant differences between the groups in academic history, social and family situation, and the adoption of risk behaviors during adolescence and early adulthood. Secondly, some of these differences were related to diagnosis (ADHD versus non-ADHD) while others were related to the sample being examined (prison versus psychiatric). The findings from the study showed the presence of significant implications in social, family, educational, and employment achievements both for adults with ADHD (both prison and psychiatric samples) and for adults without ADHD.Este estudio tiene como objetivo describir y comparar los perfiles educativos, sociales y familiares de un grupo de adultos con y sin TDAH de dos muestras diferentes: una de carcelarios y una población clínica. Formaron parte del estudio 542 participantes, con edades comprendidas entre los 17 y 69 años. La muestra se dividió en cuatro grupos, un grupo de carcelarios con TDAH (n = 69) y sin TDAH (n = 183) y un grupo clínico con TDAH (n = 218) y sin TDAH (n = 72). Los resultados apoyan la hipótesis inicial, que establece que, primero, hay diferencias estadísticamente significativas entre los grupos en cuanto a historial académico, situación social y familiar y la adopción de conductas de riesgo durante la adolescencia y la adultez temprana; en segundo lugar, algunas de las diferencias se relacionarán con el diagnóstico de TDAH, mientras que otras estarán más vinculadas a la población examinada. Los hallazgos del estudio mostraron la presencia de consecuencias significativas para los contextos sociales, familiares, educativos y laborales tanto en poblaciones adultas con TDAH (pacientes en carcelarios y clínicos) como aquellas sin TDAH.This work was supported by the Regional Government of Asturias under Grant [FC-15-GRUPIN14-053]

Psychosocial Profiles of Adults with ADHD: A Comparative Study of Prison and Outpatient Psychiatric Samples

This study aimed to describe and compare the educational, social, and family profiles of adults with and without ADHD from two different settings: a prison and an outpatient psychiatric setting. A total of 542 participants, aged between 17 and 69 years, took part in the study. The participants consisted of four groups: a prison sample with ADHD (n = 69) and without ADHD (n = 183), and an outpatient psychiatric sample with ADHD (n = 218) and without ADHD (n = 72). The results showed that, firstly, there were some statistically significant differences between the groups in academic history, social and family situation, and the adoption of risk behaviors during adolescence and early adulthood. Secondly, some of these differences were related to diagnosis (ADHD versus non-ADHD) while others were related to the sample being examined (prison versus psychiatric). The findings from the study showed the presence of significant implications in social, family, educational, and employment achievements both for adults with ADHD (both prison and psychiatric samples) and for adults without ADHD

ADGRL3 (LPHN3) variants predict substance use disorder

Factors genètics; Desordre d'ús de substànciesFactores genéticos; Desorden de uso de sustanciasGenetic factors; Substance use disorder; ADGRL3 (LPHN3)Genetic factors are strongly implicated in the susceptibility to develop externalizing syndromes such as attention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder, conduct disorder, and substance use disorder (SUD). Variants in the ADGRL3 (LPHN3) gene predispose to ADHD and predict ADHD severity, disruptive behaviors comorbidity, long-term outcome, and response to treatment. In this study, we investigated whether variants within ADGRL3 are associated with SUD, a disorder that is frequently co-morbid with ADHD. Using family-based, case-control, and longitudinal samples from disparate regions of the world (n = 2698), recruited either for clinical, genetic epidemiological or pharmacogenomic studies of ADHD, we assembled recursive-partitioning frameworks (classification tree analyses) with clinical, demographic, and ADGRL3 genetic information to predict SUD susceptibility. Our results indicate that SUD can be efficiently and robustly predicted in ADHD participants. The genetic models used remained highly efficient in predicting SUD in a large sample of individuals with severe SUD from a psychiatric institution that were not ascertained on the basis of ADHD diagnosis, thus identifying ADGRL3 as a risk gene for SUD. Recursive-partitioning analyses revealed that rs4860437 was the predominant predictive variant. This new methodological approach offers novel insights into higher order predictive interactions and offers a unique opportunity for translational application in the clinical assessment of patients at high risk for SUDR01 DA039881/DA/NIDA NIH HHS/United States. DA039881/U.S. Department of Health & Human Services NIH, National Institute on Drug Abuse (NIDA)

Insomnia Disorder in Adult Attention-Deficit/Hyperactivity Disorder Patients: Clinical, Comorbidity, and Treatment Correlates

Trastorn per dèficit d'atenció i hiperactivitat; Comorbilitat; Trastorn d'insomniTrastorno por déficit de atención e hiperactividad; Comorbilidad; Trastorno de insomnioAttention deficit and hyperactivity disorder; Comorbidity; Insomnia disorderIntroduction: Several investigations have been performed on insomnia symptoms in adult attention-deficit/hyperactivity disorder (ADHD). However, the relationship between insomnia disorder and adult ADHD has been neglected in research. The main objective of the current study is to analyze the differences between adult ADHD patients with and without insomnia disorder, in terms of ADHD clinical severity, medical and psychiatric comorbidity, psychopharmacological treatment, and quality of life. Material and Methods: Two hundred and fifty-two adult patients with ADHD (mean age 37.60 ± 13.22 years; ADHD presentations—combined: 56.7%, inattentive: 39.7%, hyperactive/impulsive: 3.6%) were evaluated with an exhaustive clinical and psychological evaluation protocol including semistructured interviews (for comorbidities and ADHD assessment) and symptom rating scales for ADHD. The diagnosis of ADHD and insomnia disorder was made according to DSM-5 criteria. Furthermore, the Pittsburgh Sleep Quality Index, Insomnia Severity Index, and Epworth Sleepiness Scale were administered. Results: Insomnia disorder was found in 44.4% of adult ADHD patients and was more common in combined presentation (64.3%) and in patients with more ADHD severity. Comorbidities (both medical and psychiatric), especially mood disorders (42%), anxiety disorder (26.8%), personality disorder (39.3%), and any substance use disorder (11.6%), were associated with a higher insomnia disorder prevalence. ADHD stimulant treatment was related to lower insomnia disorder compared to patients without medication, as well as ADHD stable treatment. Additionally, worse health-related quality of life was associated with insomnia disorder. Conclusion: Insomnia disorder is highly prevalent in adult ADHD and is related to higher ADHD severity and more psychiatric and medical comorbidities. Some stimulants and stable pharmacological ADHD treatment are associated with better outcomes of insomnia disorder.The research leading to these results has received funding from the Instituto de Salud Carlos III (PI18/01788) and supported by the EU's Horizon 2020 Programme (Grant No. 667302, CoCA and Grant No. 728018 Eat2beNICE)

Comprehensive analysis of omics data identifies relevant gene networks for Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder that results from the interaction of both genetic and environmental risk factors. Genome-wide association studies have started to identify multiple genetic risk loci associated with ADHD, however, the exact causal genes and biological mechanisms remain largely unknown. We performed a multi-step analysis to identify and characterize modules of co-expressed genes associated with ADHD using data from peripheral blood mononuclear cells of 270 ADHD cases and 279 controls. We identified seven ADHD-associated modules of co-expressed genes, some of them enriched in both genetic and epigenetic signatures for ADHD and in biological pathways relevant for psychiatric disorders, such as the regulation of gene expression, epigenetics and immune system. In addition, for some of the modules, we found evidence of potential regulatory mechanisms, including microRNAs and common genetic variants. In conclusion, our results point to promising genes and pathways for ADHD, supporting the use of peripheral blood to assess gene expression signatures in psychiatric disorders. Furthermore, they highlight that the combination of multi-omics signals provides deeper and broader insights into the biological mechanisms underlying ADH

Gut microbiota signature in treatment-naïve attention-deficit/hyperactivity disorder

TDAH; Comunitat científicaTDAH; Comunidad científicaADHD; Scientific communityCompelling evidence supports alterations in gut microbial diversity, bacterial composition, and/or relative abundance of several bacterial taxa in attention-deficit/hyperactivity disorder (ADHD). However, findings for ADHD are inconsistent among studies, and specific gut microbiome signatures for the disorder remain unknown. Given that previous studies have mainly focused on the pediatric form of the disorder and involved small sample sizes, we conducted the largest study to date to compare the gastrointestinal microbiome composition in 100 medication-naïve adults with ADHD and 100 sex-matched healthy controls. We found evidence that ADHD subjects have differences in the relative abundance of several microbial taxa. At the family level, our data support a lower relative abundance of Gracilibacteraceae and higher levels of Selenomonadaceae and Veillonellaceae in adults with ADHD. In addition, the ADHD group showed higher levels of Dialister and Megamonas and lower abundance of Anaerotaenia and Gracilibacter at the genus level. All four selected genera explained 15% of the variance of ADHD, and this microbial signature achieved an overall sensitivity of 74% and a specificity of 71% for distinguishing between ADHD patients and healthy controls. We also tested whether the selected genera correlate with age, body mass index (BMI), or scores of the ADHD rating scale but found no evidence of correlation between genera relative abundance and any of the selected traits. These results are in line with recent studies supporting gut microbiome alterations in neurodevelopment disorders, but further studies are needed to elucidate the role of the gut microbiota on the ADHD across the lifespan and its contribution to the persistence of the disorder from childhood to adulthood

Inflammatory biotype of ADHD is linked to chronic stress: a data-driven analysis of the inflammatory proteome

ADHD; Chronic stress; Inflammatory proteomeTDAH; Estrès crònic; Proteoma inflamatoriTDAH; Estrés crónico; Proteoma inflamatorioThe association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p < 0.001), a higher clinical global impression scale score (p = 0.030), and a higher risk for suicide (p = 0.032). Medication status did not influence protein levels significantly (p ≥ 0.074), but psychotropic co-medication (p ≤ 0.009) did. In conclusion, our data suggest the presence of two distinct biotypes in adults with ADHD. Higher levels of inflammatory proteins in ADHD are linked to higher levels of chronic perceived stress in a linear fashion. Further research on inflammation in adults with ADHD should take stress levels into account.Open Access funding enabled and organized by Projekt DEAL

Treating impulsivity with probiotics in adults (PROBIA)

Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota-gut-brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity.This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression-Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18-65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up.This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients.ClinicalTrials.gov, NCT03495375. Registered on 26 February 2018

Integrative genomic analysis of methylphenidate response in attention-deficit/hyperactivity disorder

Methylphenidate (MPH) is the most frequently used pharmacological treatment in children with attention-deficit/hyperactivity disorder (ADHD). However, a considerable interindividual variability exists in clinical outcome. Thus, we performed a genome-wide association study of MPH efficacy in 173 ADHD paediatric patients. Although no variant reached genome-wide significance, the set of genes containing single-nucleotide polymorphisms (SNPs) nominally associated with MPH response (P < 0.05) was significantly enriched for candidates previously studied in ADHD or treatment outcome. We prioritised the nominally significant SNPs by functional annotation and expression quantitative trait loci (eQTL) analysis in human brain, and we identified 33 SNPs tagging cis-eQTL in 32 different loci (referred to as eSNPs and eGenes, respectively). Pathway enrichment analyses revealed an over-representation of genes involved in nervous system development and function among the eGenes. Categories related to neurological diseases, psychological disorders and behaviour were also significantly enriched. We subsequently meta-analysed the association with clinical outcome for the 33 eSNPs across the discovery sample and an independent cohort of 189 ADHD adult patients (target sample) and we detected 15 suggestive signals. Following this comprehensive strategy, our results provide a better understanding of the molecular mechanisms implicated in MPH treatment effects and suggest promising candidates that may encourage future studies

Exome chip analyses in adult attention deficit hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAFgreater than or equal to1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E−06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E−08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E−07); the PSD locus (P=7.58E−08) and ZCCHC4 locus (P=1.79E−06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E−05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD