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1.
Mol Psychiatry ; 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33483693

RESUMO

Although large genome-wide association studies (GWAS) of major depressive disorder (MDD) have identified many significant loci, the SNP-based heritability remains notably low, which might be due to etiological heterogeneity in existing samples. Here, we test the utility of targeting the severe end of the MDD spectrum through genome-wide SNP genotyping of 2725 cases who received electroconvulsive therapy (ECT) for a major depressive episode (MDE) and 4035 controls. A subset of cases (n = 1796) met a narrow case definition (MDE occurring in the context of MDD). Standard GWAS quality control procedures and imputation were conducted. SNP heritability and genetic correlations with other traits were estimated using linkage disequilibrium score regression. Results were compared with MDD cases of mild-moderate severity receiving internet-based cognitive behavioral therapy (iCBT) and summary results from the Psychiatric Genomics Consortium (PGC). The SNP-based heritability was estimated at 29-34% (SE: 6%) for the narrow case definition, considerably higher than the 6.5-8.0% estimate in the most recent PGC MDD study. Our severe MDE cases had smaller genetic correlations with neurodevelopmental disorders and neuroticism than PGC MDD cases but higher genetic risk scores for bipolar disorder than iCBT MDD cases. One genome-wide significant locus was identified (rs114583506, P = 5e-8) in an intron of HLA-B in the major histocompatibility locus on chr6. These results indicate that individuals receiving ECT for an MDE have higher burden of common variant risk loci than individuals with mild-moderate MDD. Furthermore, severe MDE shows stronger relations with other severe adult-onset psychiatric disorders but weaker relations with personality and stress-related traits than mild-moderate MDD. These findings suggest a different genetic architecture at the severest end of the spectrum, and support further study of the severest MDD cases as an extreme phenotype approach to understand the etiology of MDD.

2.
Eur Neuropsychopharmacol ; 44: 105-120, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33483252

RESUMO

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

3.
Mol Psychiatry ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712720

RESUMO

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

4.
Transl Psychiatry ; 9(1): 150, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123309

RESUMO

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/estatística & dados numéricos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Criança , Humanos
5.
Mol Psychiatry ; 24(4): 484-490, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30410065

RESUMO

Major depressive disorder is heritable and a leading cause of disability. Cognitive behavior therapy is an effective treatment for major depression. By quantifying genetic risk scores based on common genetic variants, the aim of this report was to explore the utility of psychiatric and cognitive trait genetic risk scores, for predicting the response of 894 adults with major depressive disorder to cognitive behavior therapy. The participants were recruited in a psychiatric setting, and the primary outcome score was measured using the Montgomery Åsberg Depression Rating Scale-Self Rated. Single-nucleotide polymorphism genotyping arrays were used to calculate the genomic risk scores based on large genetic studies of six phenotypes: major depressive disorder, bipolar disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, intelligence, and educational attainment. Linear mixed-effect models were used to test the relationships between the six genetic risk scores and cognitive behavior therapy outcome. Our analyses yielded one significant interaction effect (B = 0.09, p < 0.001): the autism spectrum disorder genetic risk score correlated with Montgomery Åsberg Depression Rating Scale-Self Rated changes during treatment, and the higher the autism spectrum disorder genetic load, the less the depressive symptoms decreased over time. The genetic risk scores for the other psychiatric and cognitive traits were not related to depressive symptom severity or change over time. Our preliminary results indicated, as expected, that the genomics of the response of patients with major depression to cognitive behavior therapy were complex and that future efforts should aim to maximize sample size and limit subject heterogeneity in order to gain a better understanding of the use of genetic risk factors to predict treatment outcome.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Adulto , Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Biomarcadores , Depressão/genética , Transtorno Depressivo Maior/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Herança Multifatorial/genética , Dados Preliminares , Prognóstico , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
7.
J Consult Clin Psychol ; 83(5): 902-14, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26009780

RESUMO

OBJECTIVE: Internet-based cognitive-behavioral therapy (ICBT) has received increased attention as an innovative approach to improve access to evidence-based psychological treatments. Although the efficacy of ICBT for social anxiety disorder has been established in several studies, there is limited knowledge of its effectiveness and application in clinical psychiatric care. The purpose of this study was to evaluate the effectiveness of ICBT in the treatment of social anxiety disorder and to determine the significance of patient adherence and the clinic's years of experience in delivering ICBT. METHOD: A longitudinal cohort study was conducted using latent growth curve modeling of patients (N = 654) treated with ICBT at an outpatient psychiatric clinic between 2009 and 2013. The primary outcome measure was the Liebowitz Social Anxiety Scale-Self-Rated. RESULTS: Significant reductions in symptoms of social anxiety were observed after treatment (effect size d = 0.86, 99% CI [0.74, 0.98]). Improvements were sustained at 6-month follow-up (d = 1.15, 99% CI [0.99, 1.32]). Patient adherence had a positive effect on the rate of improvement. A positive association between the clinic's years of experience with ICBT and treatment outcome was also observed. CONCLUSIONS: This study suggests that ICBT for social anxiety disorder is effective when delivered within the context of a unit specialized in Internet-based psychiatric care and may be considered as a treatment alternative for implementation within the mental health care system.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Internet , Transtornos Fóbicos/terapia , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/psicologia , Cooperação do Paciente/estatística & dados numéricos , Transtornos Fóbicos/psicologia , Resultado do Tratamento , Adulto Jovem
8.
PLoS One ; 10(4): e0124258, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25893687

RESUMO

OBJECTIVE: A central goal of health care is to improve patient outcomes. Although several studies have demonstrated the effectiveness of therapist guided internet-based cognitive behaviour therapy (ICBT) for social anxiety disorder (SAD), a significant proportion of patients do not respond to treatment. Consequently, the aim of this study was to identify individual characteristics and treatment program related factors that could help clinicians predict treatment outcomes and adherence for individuals with SAD. METHOD: The sample comprised longitudinal data collected during a 4-year period of adult individuals (N = 764) treated for SAD at a public service psychiatric clinic. Weekly self-rated Liebowitz Social Anxiety Scale (LSAS-SR) scores were provided. Rates of symptomatic change during treatment and adherence levels were analysed using multilevel modelling. The following domains of prognostic variables were examined: (a) socio-demographic variables; (b) clinical characteristics; (c) family history of mental illness; and (d) treatment-related factors. RESULTS: Higher treatment credibility and adherence predicted a faster rate of improvement during treatment, whereas higher overall functioning level evidenced a slower rate of improvement. Treatment credibility was the strongest predictor of greater adherence. Having a family history of SAD-like symptoms was also associated with greater adherence, whereas Attention-Deficit/Hyperactivity Disorder (ADHD)-like symptoms, male gender, and family history of minor depression predicted lower adherence. Also, the amount of therapist time spent per treatment module was negatively associated with adherence. CONCLUSIONS: Results from a large clinical sample indicate that the credibility of ICBT is the strongest prognostic factor explaining individual differences in both adherence level and symptomatic improvement. Early screening of ADHD-like symptoms may help clinicians identify patients who might need extra support or an adjusted treatment. Therapist behaviours that promote adherence may be important for treatment response, although more research is needed in order to determine what type of support would be most beneficial.


Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Aconselhamento à Distância/métodos , Internet , Adulto , Feminino , Humanos , Estudos Longitudinais , Masculino , Serviços de Saúde Mental/organização & administração , Cooperação do Paciente , Valor Preditivo dos Testes , Prognóstico , Classe Social , Inquéritos e Questionários , Resultado do Tratamento
9.
J Affect Disord ; 155: 49-58, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24238951

RESUMO

BACKGROUND: Efficacy of guided Internet-based cognitive behaviour therapy (ICBT) for depression has been demonstrated in several randomised controlled trials. Knowledge on the effectiveness of the treatment, i.e. how it works when delivered within routine care, is however scarce. The aim of this study was to investigate the effectiveness of ICBT for depression. METHODS: We conducted a cohort study investigating all patients (N=1203) who had received guided ICBT for depression between 2007 and 2013 in a routine care setting at an outpatient psychiatric clinic providing Internet-based treatment. The primary outcome measure was the Montgomery Åsberg Depression Rating Scale-Self rated (MADRS-S). RESULTS: Patients made large improvements from pre-treatment assessments to post-treatment on the primary outcome (effect size d on the MADRS-S=1.27, 99% CI, 1.14-1.39). Participants were significantly improved in terms of suicidal ideation and sleep difficulties. Improvements were sustained at 6-month follow-up. LIMITATIONS: Attrition was rather large at 6-month follow-up. However, additional data was collected through telephone interviews with dropouts and advanced statistical models indicated that missing data did not bias the findings. CONCLUSIONS: ICBT for depression can be highly effective when delivered within the context of routine psychiatric care. This study suggests that the effect sizes are at least as high when the treatment is delivered in routine psychiatric care by qualified staff as when delivered in a controlled trial setting.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Depressão/terapia , Internet , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/psicologia , Feminino , Seguimentos , Humanos , Masculino , Serviços de Saúde Mental/organização & administração , Pessoa de Meia-Idade , Satisfação do Paciente , Escalas de Graduação Psiquiátrica , Distúrbios do Início e da Manutenção do Sono , Ideação Suicida , Resultado do Tratamento , Adulto Jovem
10.
BMC Gastroenterol ; 13: 160, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24245807

RESUMO

BACKGROUND: Several studies show that psychological treatments relieve symptoms for patients suffering from irritable bowel syndrome (IBS). However, there are no consistent findings that show what patient characteristics make a psychological treatment more or less likely to result in improvement. We have previously conducted a study of a newly developed internet-delivered cognitive behavioral therapy (ICBT) that emphasized exposure to IBS symptoms and IBS-related situations and reduced symptom-related avoidance. The study showed that the treatment led to improvement in IBS symptoms compared to a waiting list and that treatment gains were maintained over a 15-18 month follow-up period. The aim of the present study was to investigate several possible predictors of short- and long-term treatment outcome in terms of symptom improvement, based on data collected in the previously conducted treatment trial. METHODS: Demographics, comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability were investigated as predictors of treatment outcome in the sample consisting of 79 participants diagnosed with IBS who had undergone 10 weeks of ICBT. Predictors that were significantly correlated with symptom levels at post-treatment and follow-up were entered into multiple regression analyses that controlled for pre-treatment symptom levels. RESULTS: There were measures within each domain, i.e., comorbid psychological distress, IBS-related fear and avoidance behaviors, and IBS-related disability, with the exception of demographic data, that were correlated with the symptom levels at post-treatment and follow-up. However, when these were entered into a multiple regression analyses that controlled for pre-treatment levels, none remained a significant predictor of the post-treatment and follow-up symptomatic status. CONCLUSIONS: The study did not find any individual characteristics that made patients more or less likely to respond to the exposure-based ICBT. The finding that comorbid psychological distress did not predict outcome is in accordance with previous studies. Reliable predictors for response to any type of psychological treatment for IBS remain to be established.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Terapia Implosiva/métodos , Síndrome do Intestino Irritável/terapia , Adulto , Transtornos de Ansiedade/complicações , Transtornos de Ansiedade/psicologia , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/psicologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Terapia Assistida por Computador/métodos , Resultado do Tratamento , Listas de Espera
11.
PLoS One ; 8(11): e79015, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24260145

RESUMO

OBJECTIVE: The role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703T polymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients. METHOD: Participants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report. RESULTS: At long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials. CONCLUSIONS: None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD. TRIAL REGISTRATION: ClinicalTrials.gov (ID-NCT0056496).


Assuntos
Transtornos de Ansiedade , Catecol O-Metiltransferase/genética , Terapia Cognitivo-Comportamental , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Transtornos do Comportamento Social , Triptofano Hidroxilase/genética , Adolescente , Adulto , Tonsila do Cerebelo , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Feminino , Seguimentos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Comportamento Social/genética , Transtornos do Comportamento Social/terapia
12.
Fam Community Health ; 28(2): 130-41, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15778627

RESUMO

Childhood overweight among lower socioeconomic, Hispanic children has increased. Interviews regarding health status and play patterns were conducted with 76 predominantly Hispanic mothers of overweight toddlers and preschoolers served by Women, Infants, and Children (WIC). Most participants believed their child was healthy and half were unconcerned about their child's weight. Most parents reported having a safe place to play and access to a playground, although gender differences were found. Access to an outside play area was related to amount of active play activities. Children watched an average of 1.7 hours per day of television. Health professionals must partner with parents to address childhood obesity.


Assuntos
Nível de Saúde , Hispano-Americanos/psicologia , Obesidade/psicologia , Pais/psicologia , Jogos e Brinquedos , Pré-Escolar , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Obesidade/etnologia , Pobreza
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