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1.
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.

2.
Transl Psychiatry ; 9(1): 42, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696812

RESUMO

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 SUD.


Assuntos
Predisposição Genética para Doença , Receptores Acoplados a Proteínas-G/genética , Receptores de Peptídeos/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Adulto Jovem
3.
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.

4.
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.

5.
Rev. neurol. (Ed. impr.) ; 66(supl.1): S109-S114, mar. 2018. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-171900

RESUMO

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) presenta una etiología compleja, atribuida principalmente a múltiples genes de susceptibilidad y factores ambientales. No obstante, los estudios genéticos de asociación han sido inconsistentes, identificando variantes genéticas de efecto moderado que explican una pequeña proporción de la heredabilidad estimada del trastorno (< 10%). Recientes estudios sugieren que la microbiota intestinal y la dieta desempeñan un papel importante en el desarrollo y los síntomas de diferentes trastornos mentales. Sin embargo, en la actualidad no existe una claridad absoluta al respecto. El presente proyecto propone un abordaje alternativo para identificar mecanismos a través de los cuales el ecosistema microbiano intestinal y la dieta podrían contribuir a la presencia del TDAH. Objetivo. Identificar biomarcadores para el TDAH a través del estudio de la microbiota intestinal. Sujetos y métodos. Estudio transversal de pacientes adultos con TDAH (n = 100) y de individuos control (n = 100). En ambos grupos se tomarán medidas de evaluación de TDAH y hábitos alimentarios. Se obtendrán muestras fecales para la extracción del ADN bacteriano, que permitirán caracterizar la microbiota intestinal de los participantes, para posteriormente realizar un estudio de asociación metagenómico e intentar correlacionar la composición bacteriana intestinal con subtipos clínicos del trastorno. Resultados y conclusiones. Se espera que la comparación de los perfiles de microbiota intestinal entre sujetos con TDAH y controles ayude a explicar la heterogeneidad clínica del trastorno e identificar nuevos mecanismos implicados en su desarrollo (AU)


Introduction. Attention deficit hyperactivity disorder (ADHD) has a complex aetiology, mainly attributed to a number of susceptibility genes and environmental factors. Genetic association studies, however, have been inconsistent and have identified genetic variants with a moderate effect that explain a small proportion of the estimated inheritability of the disorder (< 10%). Recent studies suggest that the gut microbiota and diet play an important role in the development and symptoms of different mental disorders. Nevertheless, no clear evidence exists on the issue. This project proposes an alternative approach to identify mechanisms by which the intestinal microbial ecosystem and diet could contribute to the presence of ADHD. Aim. To identify biomarkers for ADHD by examining the gut microbiota. Subjects and methods. We conducted a cross-sectional study of adult patients with ADHD (n = 100) and control subjects (n = 100). Measures of ADHD evaluation and eating habits were performed in both groups. Samples of faecal material were obtained from which to extract bacterial DNA, then used to characterise the participants’ gut microbiota. A metagenomics association study was later performed to attempt to correlate the bacterial composition of the intestine with the clinical subtypes of the disorder. Results and conclusions. Comparing the gut microbiota profiles of subjects with ADHD and controls is expected to help account for the clinical heterogeneity of the disorder and identify new mechanisms involved in its development (AU)


Assuntos
Humanos , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Microbioma Gastrointestinal , Biomarcadores/análise , Transtornos do Neurodesenvolvimento/diagnóstico , Predisposição Genética para Doença , Fatores de Risco , Estudos Transversais
6.
BMC Psychiatry ; 18(1): 40, 2018 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-29422022

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in childhood (5.3% to 7.1% worldwide prevalence), with substantial overall financial burden to children/adolescents, their families, and society. The aims of this study were to describe the clinical characteristics of children and adolescents with ADHD in Spain, estimate the associated direct/indirect costs of the disorder, and assess whether the characteristics and financial costs differed between children/adolescents adequately responding to currently available pharmacotherapies compared with children/adolescents for whom pharmacotherapies failed. METHODS: This was a multicenter, cross-sectional, descriptive analysis conducted in 15 health units representative of the overall Spanish population. Data on demographic characteristics, socio-occupational status, social relationships, clinical variables of the disease, and pharmacological and non-pharmacological treatments received were collected in 321 children and adolescents with ADHD. Direct and indirect costs were estimated over one year from both a health care system and a societal perspective. RESULTS: The estimated average cost of ADHD per year per child/adolescent was €5733 in 2012 prices; direct costs accounted for 60.2% of the total costs (€3450). Support from a psychologist/educational psychologist represented 45.2% of direct costs and 27.2% of total costs. Pharmacotherapy accounted for 25.8% of direct costs and 15.5% of total costs. Among indirect costs (€2283), 65.2% was due to caregiver expenses. The total annual costs were significantly higher for children/adolescents who responded poorly to pharmacological treatment (€7654 versus €5517; P = 0.024), the difference being mainly due to significantly higher direct costs, particularly with larger expenses for non-pharmacological treatment (P = 0.012). CONCLUSIONS: ADHD has a significant personal, familial, and financial impact on the Spanish health system and society. Successful pharmacological intervention was associated with lower overall expenses in the management of the disorder.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Cuidadores/economia , Criança , Estudos Transversais , Demografia , Emprego/economia , Feminino , Humanos , Masculino , Espanha/epidemiologia
7.
J Atten Disord ; 22(7): 679-693, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-26515892

RESUMO

OBJECTIVE: Functional imaging studies have found reduced frontal activity, mainly in dorso/ventro-lateral regions and reduced task-related de-activation of the default mode network in childhood ADHD. Adult studies are fewer and inconclusive. We aimed to investigate the potential neural bases of executive function in ADHD adults, examining brain activity during N-back task performance, and to explore the potential corrective effects of long-term methylphenidate treatment. METHOD: We recruited a large adult ADHD-combined sample and a matched control group and obtained functional magnetic resonance imaging (fMRI) images during task. ADHD participants were subdivided in a group under long-term treatment with methylphenidate (washed out for the scan) and a treatment-naive group. RESULTS: ADHD participants showed deficient de-activation of the medial prefrontal cortex during 2-back task, implying default mode network dysfunction. We found no relationship between blunted de-activation and treatment history. CONCLUSION: As de-activation failure in the medial frontal cortex is linked to lapses of attention, findings suggest a potential link to ADHD symptomatology.

8.
J Affect Disord ; 227: 117-125, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29055259

RESUMO

BACKGROUND: It is well established that patients with either bipolar disorder (BD) or attention-deficit/hyperactivity disorder (ADHD) present functional impairment even when in remission. Nevertheless, research on functional impairment with adult patients with bipolar disorder comorbid to ADHD (BD+ADHD) is very scarce. The main objective of the current report was to evaluate the overall and specific domains of functioning, in patients with BD+ADHD compared to patients with pure bipolar disorder (pBD) and healthy controls (HCs). METHOD: 162 subjects from 3 groups were compared: 63 pBD, 23 BD+ADHD and 76 HCs. All the patients with BD had been euthymic for at least 6 months and they were recruited at the Hospital Clinic of Barcelona. All the participants were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS) and the Functioning Assessment Short Test (FAST). Clinical, and sociodemographic data were also recorded. RESULTS: Clinical groups, pBD and BD+ADHD, showed lower overall functioning (p < 0.001) in each domain of the FAST scale compared to the HCs. Moreover, the Tukey post hoc test revealed that the BD+ADHD group showed a worse score than pBD in the cognitive domain of the FAST. However, after controlling for potential confounding variables, only the HDRS scores (p < 0.026) remained significant for the cognitive domain of the FAST. LIMITATIONS: The small sample size of the comorbid BD+ADHD group. CONCLUSIONS: Adult patients with BD+ADHD showed the worst scores in functioning compared with the HCs, but did not show more severe functional impairment than the pBD group except for the cognitive domain. Therefore our findings suggest that depressive symptoms in adults with BD+ADHD may negatively influence cognitive functioning. Further studies are needed to confirm our findings for the management of BD+ADHD.


Assuntos
Atividades Cotidianas/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtorno Bipolar/psicologia , Cognição/fisiologia , Depressão/psicologia , Relações Interpessoais , Ajustamento Social , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno Bipolar/complicações , Depressão/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Bipolar Disord ; 19(8): 637-650, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28941032

RESUMO

OBJECTIVE: Research on neurocognitive impairment in adult patients with comorbid bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD) is very scarce. This study assessed the neurocognitive profile of a comorbid group (BD+ADHD) compared with that of pure BD (pBD) group, pure ADHD (pADHD) group and healthy controls (HCs). METHODS: This was a three-site study comprising 229 subjects: 70 patients with pBD, 23 with BD+ADHD, 50 with pADHD, and 86 HCs. All patients with BD had been euthymic for at least 6 months. Neuropsychological performance was assessed using a comprehensive neurocognitive battery. RESULTS: Our results showed that all the clinical groups had poorer performance than the HCs in all the neurocognitive domains except for executive functions. No significant differences were observed between the pBD and BD+ADHD groups in any of the cognitive domains, with these two groups showing greater impairment than the pADHD group in executive functions and visual memory. CONCLUSIONS: Our results, although preliminary, suggest that the BD+ADHD group showed the same neurocognitive profile as pBD patients, most likely reflecting the same neurobiological basis. On the other hand, the pADHD group showed a more selective moderate impairment in attention.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno Bipolar , Transtornos Neurocognitivos , Adulto , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologia , Transtorno Bipolar/fisiopatologia , Comorbidade , Função Executiva , Feminino , Humanos , Masculino , Memória , Transtornos Neurocognitivos/diagnóstico , Transtornos Neurocognitivos/etiologia , Transtornos Neurocognitivos/psicologia , Testes Neuropsicológicos , Estatística como Assunto
10.
Eur Arch Psychiatry Clin Neurosci ; 267(6): 541-549, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27658669

RESUMO

Common environmental etiological factors between borderline personality disorder (BPD) and attention deficit/hyperactivity disorder (ADHD) have not been fully studied. The main aim of this study was to investigate the relationship between childhood trauma histories, assessed by the Childhood Trauma Questionnaire-Short Form (CTQ-SF), with adult BPD, ADHD or BPD-ADHD diagnoses. Comorbid BPD-ADHD patients exhibited significantly higher clinical severity and higher scores in the Total Neglect Scale, compared to BPD and ADHD patients, and only a marginal difference was observed for Sexual Abuse when BPD and ADHD patients were compared. Physical Trauma Scales were associated with ADHD diagnosis, whereas Emotional Abuse and Sexual Abuse Scales were associated with BPD or BPD-ADHD diagnoses. The study findings support the association between experiencing traumatic events in childhood and a higher clinical severity of BPD in adulthood. Furthermore, physical trauma history in childhood could be associated with the persistence of ADHD in adulthood and emotional or sexual abuse with later development of BPD or comorbid BPD-ADHD. Whereas experiencing childhood traumas is associated with later development of more general psychopathology, our study supports that a specific type of traumatic event could increase the risk for the consolidation of a concrete psychiatric disorder in the trajectory from childhood to adulthood of vulnerable subjects.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Transtorno da Personalidade Borderline/etiologia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno da Personalidade Borderline/diagnóstico , Feminino , Humanos , Masculino , Risco , Índice de Gravidade de Doença , Adulto Jovem
11.
Rev. neurol. (Ed. impr.) ; 64(supl.1): s117-s122, 2017. tab
Artigo em Espanhol | IBECS | ID: ibc-163045

RESUMO

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo altamente prevalente, presenta una elevada comorbilidad con sintomatología afectiva y ansiosa, afecta a la funcionalidad de la persona que lo padece, tienen una baja adhesión terapéutica y genera unos costes sociales y personales elevados. El mindfulness es un tratamiento psicológico que ha demostrado ser eficaz para el TDAH. La realidad virtual es un tratamiento altamente utilizado en fobias y extendido a otras patologías con resultados positivos. Objetivo. Desarrollar el primer tratamiento con realidad virtual y mindfulness para el TDAH en la edad adulta, que suponga un aumento en la adhesión terapéutica y reduzca costes. Pacientes y métodos. Estudio piloto de 25 pacientes tratados con realidad virtual, mediante cuatro sesiones de 30 minutos, y 25 mediante psicoestimulantes. Se tomarán medidas de evaluación pretratamiento, postratamiento y postratamiento a los 3 y 12 meses, tanto de TDAH como de depresión, ansiedad, funcionalidad y calidad de vida. Se analizarán posteriormente con el programa SPSS v. 20 y se realizará un ANOVA de grupos independientes para ver las diferencias entre tratamientos y un test-retest para detectar el mantenimiento de los cambios. Resultados y conclusiones. Es necesaria la utilización de tratamientos que sean efectivos, supongan una reducción en los costes y un aumento en la adhesión terapéutica. El tratamiento con realidad virtual se plantea como una alternativa a los tratamientos clásicos, que sea más breve y atractiva para los pacientes (AU)


Introduction. Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder, which presents a high comorbidity with anxiety and affective signs and symptoms. It has repercussions on the functioning of those suffering from it, who also have low therapy compliance and generate a significant cost both at a personal level and for society. Mindfulness is a psychological treatment that has proved to be effective for ADHD. Virtual reality is widely used as treatment in cases of phobias and other pathologies, with positive results. Aims. To develop the first treatment for ADHD in adults based on virtual reality and mindfulness, while also resulting in increased treatment adherence and reduced costs. Patients and methods. We conducted a pilot study with 25 patients treated by means of virtual reality, in four 30-minute sessions, and 25 treated with psychostimulants. Measures will be taken pre-treatment, post-treatment and at 3 and 12 months post-treatment, to evaluate both ADHD and also depression, anxiety, functionality and quality of life. Data will be later analysed with the SPSS v. 20 statistical program. An ANOVA of independent groups will be performed to see the differences between treatments and also a test-retest to detect whether the changes will be maintained. Results and conclusions. It is necessary to use treatments that are effective, reduce costs and increase therapy adherence. Treatment with virtual reality is an interesting alternative to the classical treatments, and is shorter and more attractive for patients (AU)


Assuntos
Humanos , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia de Exposição à Realidade Virtual/métodos , Terapia de Exposição à Realidade Virtual/tendências , Atenção Plena/métodos , Atenção Plena/tendências , Projetos Piloto , Análise de Variância , Adesão à Medicação , Psicoterapia Centrada na Pessoa/métodos , Psicoterapia Centrada na Pessoa/tendências , Terapia Cognitivo-Comportamental/métodos , Resultado do Tratamento
12.
Actas Esp Psiquiatr ; 44(6): 231-43, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27906414

RESUMO

INTRODUCTION: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which is frequently maintained in adolescent and adult age. It presents great clinical heterogeneity, significantly affecting the functioning of those who suffer it. Although drug treatments obtain results by themselves, the approach should be multidisciplinary and be adapted to the specific needs of each patient and his/ her family. Given the variety of drugs currently available to treat ADHD, there are diverse opinions on the most effective way to approach this disorder. The objective of this work is to study the opinion of an expert clinical panel and to know the professional criteria used to define key concepts and therapeutic guidelines of ADHD in Spain. METHODOLOGY: The project was carried out in four phases: 1) Constitution of a Scientific Committee, responsible for the preliminary biographic review and the formulation of the questionnaire; 2) selection of an expert panel of specialists with special interest and/or experience in the treatment of ADHD; 3) Likert type structured survey (online platform) in two rounds with interim processing of opinions; and 4) collection and final analysis of results. RESULTS: The experts’ panel achieved a consensus in 55 of the 58 items making up the questionnaire, finding 3 items in which sufficient unanimity of criteria was not achieved because of the high number of experts were found in positions of non-certainty. CONCLUSIONS: Overall, the experts of this study reached a high level of agreement in the criteria proposed in the survey, which could be generalized as indications for the clinical practice in the management of ADHD. Similarly, and given the dispersion of the results in some of the items and the lack of consensus in others, some points remain as object of discussion.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Consenso , Técnica Delfos , Humanos , Guias de Prática Clínica como Assunto , Espanha
13.
Actas esp. psiquiatr ; 44(6): 231-243, nov.-dic. 2016. tab
Artigo em Espanhol | IBECS | ID: ibc-158456

RESUMO

Introducción. El Trastorno por Déficit de Atención e Hiperactividad (TDAH) es uno de los trastornos del neurodesarrollo más prevalentes en la infancia, que frecuentemente se mantiene en la adolescencia y edad adulta. Presenta una gran heterogeneidad clínica, afectando notablemente al funcionamiento de quien lo padece. Si bien los tratamientos farmacológicos obtienen resultados por s. mismos, el abordaje debe ser multidisciplinar y adaptado a las necesidades específicas de cada paciente y su familia. Dada la variedad de fármacos disponibles actualmente para tratar el TDAH, existen opiniones diversas sobre cuál es la manera más efectiva de abordar este trastorno. El objetivo de este trabajo es explorar la opinión de un panel clínico experto y conocer el criterio profesional utilizado para definir conceptos clave y las pautas terapéuticas del TDAH en España. Metodología. El proyecto se efectuó en cuatro fases: 1) constitución de un Comité Científico, responsable de la revisión bibliográfica preliminar y de la formulación del cuestionario; 2) selección de un panel experto de especialistas con especial interés y/o experiencia en el tratamiento del TDAH; 3) encuesta estructurada tipo Likert (plataforma online) en dos rondas con procesamiento intermedio de opiniones; y 4) recopilación y análisis final de resultados. Resultados. El panel de expertos logró un consenso en 55 de los 58 ítems que conformaron el cuestionario, encontrando 3 ítems en los que no se consiguió suficiente unanimidad de criterio, debido a que gran cantidad de expertos se situaron en posiciones de indeterminación. Conclusiones. De manera global, los expertos de este estudio alcanzaron un elevado grado de acuerdo en los criterios propuestos en la encuesta, que podrían generalizarse como indicaciones para la práctica clínica en el manejo del TDAH Del mismo modo, y dada la dispersión de los resultados en algunos de los ítems y el no consenso en otros, quedan algunos puntos objeto de discusión (AU)


Introduction. Attention Deficit Hyperactivity Disorder (ADHD) is one of the most prevalent neurodevelopmental disorders in childhood, which is frequently maintained in adolescent and adult age. It presents great clinical heterogeneity, significantly affecting the functioning of those who suffer it. Although drug treatments obtain results by themselves, the approach should be multidisciplinary and be adapted to the specific needs of each patient and his/her family. Given the variety of drugs currently available to treat ADHD, there are diverse opinions on the most effective way to approach this disorder. The objective of this work is to study the opinion of an expert clinical panel and to know the professional criteria used to define key concepts and therapeutic guidelines of ADHD in Spain. Methodology. The project was carried out in four phases: 1) Constitution of a Scientific Committee, responsible for the preliminary biographic review and the formulation of the questionnaire; 2) selection of an expert panel of specialists with special interest and/or experience in the treatment of ADHD; 3) Likert type structured survey (online platform) in two rounds with interim processing of opinions; and 4) collection and final analysis of results. Results. The experts’ panel achieved a consensus in 55 of the 58 items making up the questionnaire, finding 3 items in which sufficient unanimity of criteria was not achieved because of the high number of experts were found in positions of non-certainty. Conclusions. Overall, the experts of this study reached a high level of agreement in the criteria proposed in the survey, which could be generalized as indications for the clinical practice in the management of ADHD. Similarly, and given the dispersion of the results in some of the items and the lack of consensus in others, some points remain as object of discussion (AU)


Assuntos
Humanos , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Consenso , Técnica Delfos , Espanha , Guias de Prática Clínica como Assunto
14.
Psychiatry Res Neuroimaging ; 254: 41-7, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27318593

RESUMO

UNLABELLED: Attention Deficit Hyperactivity Disorder (ADHD) commonly affects children, although the symptoms persist into adulthood in approximately 50% of cases. Structural imaging studies in children have documented both cortical and subcortical changes in the brain. However, there have been only a few studies in adults and the results are inconclusive. METHOD: Voxel-based morphometry (VBM) was applied to 44 adults with ADHD, Combined subtype, aged 18-54 years and 44 healthy controls matched for age, sex and IQ. RESULTS: ADHD patients showed reduced gray matter (GM) volume in the right supplementary motor area (SMA). Using more lenient thresholds we also observed reductions in the subgenual anterior cingulate (ACC) and right dorsolateral prefrontal (DLPFC) cortices and increases in the basal ganglia, specifically in the left caudate nucleus and putamen. There was a positive correlation between the cumulative stimulant dose and volume in the right SMA and DLPFC clusters. CONCLUSIONS: The findings suggest that adults with ADHD show brain structural changes in regions belonging to the so-called cool executive function network. Long-term stimulant medication may act to normalize these GM alterations.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/patologia , Função Executiva/fisiologia , Giro do Cíngulo/patologia , Imagem por Ressonância Magnética/métodos , Córtex Motor/patologia , Córtex Pré-Frontal/patologia , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Córtex Pré-Frontal/diagnóstico por imagem , Adulto Jovem
15.
Am J Med Genet B Neuropsychiatr Genet ; 171(5): 733-47, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27021288

RESUMO

Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P < 5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.


Assuntos
Agressão/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/genética , Adolescente , Adulto , Agressão/psicologia , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Criança , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
16.
Am J Med Genet B Neuropsychiatr Genet ; 168(6): 459-470, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26174813

RESUMO

Attention deficit is one of the core symptoms of the attention-deficit/hyperactivity disorder (ADHD). However, the specific genetic variants that may be associated with attention function in adult ADHD remain largely unknown. The present study aimed to identifying SNPs associated with attention function in adult ADHD and tested whether these associations were enriched for specific biological pathways. Commissions, hit-reaction time (HRT), the standard error of HRT (HRTSE), and intraindividual coefficient variability (ICV) of the Conners Continuous Performance Test (CPT-II) were assessed in 479 unmedicated adult ADHD individuals. A Genome-Wide Association Study (GWAS) was conducted for each outcome and, subsequently, gene set enrichment analyses were performed. Although no SNPs reached genome-wide significance (P < 5E-08), 27 loci showed suggestive evidence of association with the CPT outcomes (P < E-05). The most relevant associated SNP was located in the SORCS2 gene (P = 3.65E-07), previously associated with bipolar disorder (BP), Alzheimer disease (AD), and brain structure in elderly individuals. We detected other genes suggested to be involved in synaptic plasticity, cognitive function, neurological and neuropsychiatric disorders, and smoking behavior such as NUAK1, FGF20, NETO1, BTBD9, DLG2, TOP3B, and CHRNB4. Also, several of the pathways nominally associated with the CPT outcomes are relevant for ADHD such as the ubiquitin proteasome, neurodegenerative disorders, axon guidance, and AD amyloid secretase pathways. To our knowledge, this is the first GWAS and pathway analysis of attention function in patients with persistent ADHD. Overall, our findings reinforce the conceptualization of attention function as a potential endophenotype for studying the molecular basis of adult ADHD. © 2015 Wiley Periodicals, Inc.

17.
Rev Neurol ; 60 Suppl 1: S115-20, 2015 Feb 25.
Artigo em Espanhol | MEDLINE | ID: mdl-25726815

RESUMO

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that may become manifest at any time in life. In 50-70% of children diagnosed with the disorder it presents in adolescence. Young people with ADHD have high rates of comorbidity with other psychiatric disorders and a high degree of functional compromise. AIMS: To review the literature on cognitive-behavioural interventions that have been applied to the treatment of ADHD in adolescence. DEVELOPMENT: The studies that have been conducted on psychological treatment to date were reviewed, and the interventions were classified into: psychosocial treatments, mindfulness therapy and cognitive-behavioural treatment (individual and in groups). The only study on cognitive-behavioural therapy for adolescents with ADHD is also reviewed, as well as a new intervention protocol for application to groups designed at the Hospital Universitari Vall d'Hebron. CONCLUSIONS: Although there has been a recent increase in the number of publications dealing with the psychological treatment of ADHD in adolescents, there is a need for a greater development of intervention protocols and studies on their efficacy/effectiveness.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia Cognitivo-Comportamental , Adolescente , Humanos , Psicoterapia
18.
Rev. neurol. (Ed. impr.) ; 60(supl.1): s115-s120, mar. 2015. tab
Artigo em Espanhol | IBECS | ID: ibc-134382

RESUMO

Introducción. El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo que se puede manifestar a lo largo de la vida. Un 50-70% de los niños diagnosticados presenta el trastorno en la adolescencia. Los jóvenes con TDAH tienen elevadas tasas de comorbilidad con otros trastornos psiquiátricos y una elevada afectación funcional. Objetivo. Revisar la bibliografía de las intervenciones cognitivo-conductuales que se han aplicado al tratamiento del TDAH en la adolescencia. Desarrollo. Se revisan los estudios sobre tratamiento psicológico, clasificando las intervenciones en: tratamientos psicosociales, tratamiento en mindfulness y tratamiento cognitivo-conductual (individual y en formato de grupo). Se revisa el único estudio publicado sobre terapia cognitivo-conductual para adolescentes con TDAH, así como un nuevo protocolo de intervención en formato de grupo diseñado en el Hospital Universitari Vall d’Hebron. Conclusiones. Aunque recientemente se ha incrementado el número de publicaciones sobre el tratamiento psicológico del TDAH en el adolescente, se requiere un desarrollo mayor de protocolos de intervención y estudios sobre la eficacia/ efectividad de éstos (AU)


Introduction. Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that may become manifest at any time in life. In 50-70% of children diagnosed with the disorder it presents in adolescence. Young people with ADHD have high rates of comorbidity with other psychiatric disorders and a high degree of functional compromise. Aims. To review the literature on cognitive-behavioural interventions that have been applied to the treatment of ADHD in adolescence. Development. The studies that have been conducted on psychological treatment to date were reviewed, and the interventions were classified into: psychosocial treatments, mindfulness therapy and cognitive-behavioural treatment (individual and in groups). The only study on cognitive-behavioural therapy for adolescents with ADHD is also reviewed, as well as a new intervention protocol for application to groups designed at the Hospital Universitari Vall d’Hebron. Conclusions. Although there has been a recent increase in the number of publications dealing with the psychological treatment of ADHD in adolescents, there is a need for a greater development of intervention protocols and studies on their efficacy/effectiveness (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Terapia Cognitivo-Comportamental/classificação , Terapia Cognitivo-Comportamental/métodos , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia Cognitivo-Comportamental/instrumentação , Terapia Cognitivo-Comportamental , Transtornos de Ansiedade/prevenção & controle , Transtornos de Ansiedade/psicologia
19.
Neuropsychopharmacology ; 40(4): 915-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25284319

RESUMO

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with high heritability. At least 30% of patients diagnosed in childhood continue to suffer from ADHD during adulthood and genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. To date, genome-wide association studies (GWAS) of ADHD have been completed in seven independent datasets, six of which were pediatric samples and one on persistent ADHD using a DNA-pooling strategy, but none of them reported genome-wide significant associations. In an attempt to unravel novel genes for the persistence of ADHD into adulthood, we conducted the first two-stage GWAS in adults with ADHD. The discovery sample included 607 ADHD cases and 584 controls. Top signals were subsequently tested for replication in three independent follow-up samples of 2104 ADHD patients and 1901 controls. None of the findings exceeded the genome-wide threshold for significance (PGC<5e-08), but we found evidence for the involvement of the FBXO33 (F-box only protein 33) gene in combined ADHD in the discovery sample (P=9.02e-07) and in the joint analysis of both stages (P=9.7e-03). Additional evidence for a FBXO33 role in ADHD was found through gene-wise and pathway enrichment analyses in our genomic study. Risk alleles were associated with lower FBXO33 expression in lymphoblastoid cell lines and with reduced frontal gray matter volume in a sample of 1300 adult subjects. Our findings point for the first time at the ubiquitination machinery as a new disease mechanism for adult ADHD and establish a rationale for searching for additional risk variants in ubiquitination-related genes.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/genética , Proteínas F-Box/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Rev Neurol ; 58 Suppl 1: S19-24, 2014 Feb 24.
Artigo em Espanhol | MEDLINE | ID: mdl-25252662

RESUMO

The existing literature that reports findings linked with the involvement of neurotrophic factors in attention deficit hyperactivity disorder (ADHD) is reviewed. Neurotrophins, a family of neurotrophic factors, are a kind of proteins that are specific to the nervous system and play an essential role in neuron survival, differentiation and proliferation during the development of the central and peripheral nervous system. These molecules stimulate axonal growth and exert an influence on the connections with the target tissue in order to establish the synaptic connections. The study of neurotrophins in ADHD, a neurodevelopmental disorder, is of interest mainly due to the functions that these proteins perform in the central nervous system. Studies on animal, pharmacological and molecular genetic models yield evidence that relates neurotrophins with the disorder. This work reviews the results from the studies conducted to date on ADHD and neurotrophic factors, especially brain-derived neurotrophic factor (BDNF). Thus, although pharmacological studies suggest that the response to atomoxetine in adults with ADHD is not directly mediated by the effect on the BDNF, reductions in BDNF levels in the plasma of adult patients with ADHD have been reported. Further studies with broader samples and greater control of environmental factors that can regulate neurotrophin expression, such as diet, physical exercise and situations of social risk, are needed to be able to determine the role they play in the aetiology of ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Fatores de Crescimento Neural/fisiologia , Adulto , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/deficiência , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Estimulantes do Sistema Nervoso Central/farmacologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Fatores de Crescimento Neural/biossíntese , Fatores de Crescimento Neural/genética , Mutação Puntual , Receptor trkB/efeitos dos fármacos , Receptor trkB/genética , Sinapses/fisiologia
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