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1.
Transl Psychiatry ; 10(1): 330, 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989213

RESUMO

While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144,818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p < 1.77 × 10-5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p < 1.99 × 10-3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p < 0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

2.
Mol Psychiatry ; 2020 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-32488124

RESUMO

Humans differ substantially in how strongly they respond to similar experiences. Theory suggests that such individual differences in susceptibility to environmental influences have a genetic basis. The present study investigated the genetic architecture of Environmental Sensitivity (ES) by estimating its heritability, exploring the presence of multiple heritable components and its genetic overlap with common personality traits. ES was measured with the Highly Sensitive Child (HSC) questionnaire and heritability estimates were obtained using classic twin design methodology in a sample of 2868 adolescent twins. Results indicate that the heritability of sensitivity was 0.47, and that the genetic influences underlying sensitivity to negative experiences are relatively distinct from sensitivity to more positive aspects of the environment, supporting a multi-dimensional genetic model of ES. The correlation between sensitivity, neuroticism and extraversion was largely explained by shared genetic influences, with differences between these traits mainly attributed to unique environmental influences operating on each trait.

3.
Sleep Med ; 66: 174-183, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31901759

RESUMO

OBJECTIVE/BACKGROUND: Many patients find cognitive behavioral therapy for insomnia (CBT-I) useful. However, it is currently unknown if those with sub-threshold insomnia also benefit. Here we assessed whether CBT-I is both feasible and acceptable in participants with sub-threshold insomnia. The primary aims were to evaluate participation rates and treatment acceptability, and to establish an effect size for symptom improvement. PATIENTS/METHODS: A total of 199 female participants (Mage 20 ± 5 years) took part. Following baseline assessments, participants were randomly allocated to either a six-week digital CBT-I intervention or a six-week control group receiving puzzles. Additional assessments were performed three-weeks, six-weeks, and six-months later. RESULTS: Participation rates at each survey assessment wave did not differ between the groups (ps > 0.140), though adherence to completing each weekly task was lower in the CBT-I group, p = 0.02. Treatment acceptability was high (M (SD) = 33.61 (4.82), theoretical range 6-42). The CBT-I group showed greater improvement in insomnia symptoms at the end of the intervention compared to the control group (p = 0.013, d = 0.42), with significant variation in outcome (M = 4.69, SD = 5.41). Sub-threshold participants showed a similar pattern of results, whilst those meeting insomnia criteria showed a smaller between-group difference. CBT-I led to improvements in anxiety, paranoia and perceived stress between baseline and end of intervention. Changes in insomnia symptoms were mediated by cognitions about sleep and somatic pre-sleep arousal. CONCLUSIONS: CBT-I provides a benefit even in sub-threshold insomnia. CBT-I may be useful to tackle insomnia symptoms even when they are sub-threshold.

4.
Psychol Assess ; 31(8): 1006-1018, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31070449

RESUMO

Questionnaire measures offer a time and cost-effective alternative to full diagnostic assessments for identifying and differentiating between potential anxiety disorders and are commonly used in clinical practice. Little is known, however, about the capacity of questionnaire measures to detect specific anxiety disorders in clinically anxious preadolescent children. This study aimed to establish the ability of the Spence Children's Anxiety Scale (SCAS) subscales to identify children with specific anxiety disorders in a large clinic-referred sample (N = 1,438) of children aged 7 to 12 years. We examined the capacity of the Separation Anxiety, Social Phobia, Generalized Anxiety, and Physical Injury Fears (phobias) subscales to discriminate between children with and without the target disorder. We also identified optimal cutoff scores on subscales for accurate identification of children with the corresponding disorder, and examined the contribution of child, mother, and father reports. The Separation Anxiety subscale was able to accurately identify children with separation anxiety disorder, and this was replicated across all 3 reporters. Mother- and father-reported Social Phobia subscales also accurately identified children with social anxiety disorder, although child report was only able to accurately detect social anxiety disorder in girls. Using 2 or more reporters improved the sensitivity of the Separation Anxiety and Social Phobia subscales but reduced specificity. The Generalized Anxiety and Physical Injury Fears subscales failed to accurately identify children with the corresponding disorders. These findings have implications for the potential use of mother-, father-, and child-report SCAS subscales to detect specific disorders in preadolescent children in clinical settings. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Transtornos de Ansiedade/diagnóstico , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Inquéritos e Questionários/estatística & dados numéricos , Criança , Feminino , Humanos , Masculino , Mães , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
5.
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
6.
Am J Med Genet B Neuropsychiatr Genet ; 180(2): 150-158, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30334356

RESUMO

Differential DNA methylation of the hypothalamic-pituitary-adrenal axis related gene FKBP5 has recently been shown to be associated with varying response to environmental influences and may play a role in how well people respond to psychological treatments. Participants (n = 111) received exposure-based cognitive behavioural therapy (CBT) for agoraphobia with or without panic disorder, or specific phobias. Percentage DNA methylation levels were measured for the promoter region and intron 7 of FKBP5. The association between percentage reduction in clinical severity and change in DNA methylation was tested using linear mixed models. The effect of genotype (rs1360780) was tested by the inclusion of an interaction term. The association between change in DNA methylation and FKBP5 expression was examined. Change in percentage DNA methylation at one CpG site of intron 7 was associated with percentage reduction in severity (ß = -4.26, p = 3.90 × 10-4 ), where a decrease in DNA methylation was associated with greater response to therapy. An interaction was detected between rs1360780 and changes in DNA methylation in the promoter region of FKBP5 on treatment outcome (p = .045) but did not survive correction for multiple testing. Changes in DNA methylation were not associated with FKBP5 expression. Decreasing DNA methylation at one CpG site of intron 7 of FKBP5 was strongly associated with decreasing anxiety severity following exposure-based CBT. In addition, there was suggestive evidence that allele-specific methylation at the promoter region may also be associated with treatment response. The results of this study add to the growing literature demonstrating the role of biological processes such as DNA methylation in response to environmental influences.


Assuntos
Agorafobia/genética , Terapia Implosiva/métodos , Proteínas de Ligação a Tacrolimo/genética , Adulto , Idoso , Agorafobia/terapia , Terapia Cognitivo-Comportamental/métodos , Metilação de DNA/genética , Epigênese Genética/genética , Feminino , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Íntrons/genética , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Proteínas de Ligação a Tacrolimo/metabolismo , Resultado do Tratamento
7.
J Child Psychol Psychiatry ; 59(7): 763-772, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29520926

RESUMO

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


Assuntos
Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Avaliação de Processos e Resultados em Cuidados de Saúde , Pais , Psicoterapia de Grupo/métodos , Ansiedade de Separação/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fobia Social/terapia , Transtornos Fóbicos/terapia , Indução de Remissão , Índice de Gravidade de Doença
8.
Semin Cell Dev Biol ; 77: 133-143, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29051054

RESUMO

Empirical studies suggest that psychiatric disorders result from a complex interplay between genetic and environmental factors. Most evidence for such gene-environment interaction (GxE) is based on single candidate gene studies conducted from a Diathesis-Stress perspective. Recognizing the short-comings of candidate gene studies, GxE research has begun to focus on genome-wide and polygenic approaches as well as drawing on different theoretical concepts underlying GxE, such as Differential Susceptibility. After reviewing evidence from candidate GxE studies and presenting alternative theoretical frameworks underpinning GxE research, more recent approaches and findings from whole genome approaches are presented. Finally, we suggest how future GxE studies may unpick the complex interplay between genes and environments in psychiatric disorders.


Assuntos
Interação Gene-Ambiente , Predisposição Genética para Doença/genética , Transtornos Mentais/genética , Estresse Psicológico/genética , Estresse Psicológico/psicologia , Transtorno da Personalidade Antissocial/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Catecol O-Metiltransferase/genética , Depressão/genética , Meio Ambiente , Humanos , Monoaminoxidase/genética , Receptores de Dopamina D4/genética , Esquizofrenia/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética
9.
BMC Psychol ; 5(1): 41, 2017 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-29284537

RESUMO

BACKGROUND: Optimal psychological development is dependent upon a complex interplay between individual and situational factors. Investigating the development of these factors in adolescence will help to improve understanding of emotional vulnerability and resilience. The CogBIAS longitudinal study (CogBIAS-L-S) aims to combine cognitive and genetic approaches to investigate risk and protective factors associated with the development of mood and impulsivity-related outcomes in an adolescent sample. METHODS: CogBIAS-L-S is a three-wave longitudinal study of typically developing adolescents conducted over 4 years, with data collection at age 12, 14 and 16. At each wave participants will undergo multiple assessments including a range of selective cognitive processing tasks (e.g. attention bias, interpretation bias, memory bias) and psychological self-report measures (e.g. anxiety, depression, resilience). Saliva samples will also be collected at the baseline assessment for genetic analyses. Multilevel statistical analyses will be performed to investigate the developmental trajectory of cognitive biases on psychological functioning, as well as the influence of genetic moderation on these relationships. DISCUSSION: CogBIAS-L-S represents the first longitudinal study to assess multiple cognitive biases across adolescent development and the largest study of its kind to collect genetic data. It therefore provides a unique opportunity to understand how genes and the environment influence the development and maintenance of cognitive biases and provide insight into risk and protective factors that may be key targets for intervention.


Assuntos
Cognição , Variação Genética , Psicologia do Adolescente , Adolescente , Ansiedade/genética , Criança , Depressão/genética , Depressão/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Memória
10.
BMJ Open ; 7(11): e017177, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29196479

RESUMO

INTRODUCTION: Cognitive-behavioural therapy for insomnia (CBT-I) leads to insomnia symptom improvements in a substantial proportion of patients. However, not everyone responds well to this treatment, and it is unclear what determines individual differences in response. The broader aim of this work is to examine to what extent response to CBT-I is due to genetic and environmental factors. The purpose of this pilot study is to examine feasibility of a design to test hypotheses focusing on an unselected sample, that is, without selection on insomnia complaints, in order to plan a larger behavioural genetics study where most participants will likely not have an insomnia disorder. METHODS AND ANALYSIS: A two parallel-group randomised controlled trial is being conducted across three London universities. Female students (minimum age 18 years) enrolled on a psychology programme at one of the three sites were invited to participate. The target number of participants to be recruited is 240. Following baseline assessments, participants were randomly allocated to either the treatment group, where they received weekly sessions of digital CBT-I for 6 weeks, or the control group, where they completed an online puzzle each week for 6 weeks. Follow-up assessments have taken place mid-intervention (3 weeks) and end of intervention (6 weeks). A 6-month follow-up assessment will also occur. Primary outcomes will be assessed using descriptive statistics and effect size estimates for intervention effects. Secondary outcomes will be analysed using multivariate generalised estimating equation models. ETHICS AND DISSEMINATION: The study received ethical approval from the Research Ethics and Integrity subcommittee, Goldsmiths, University of London (application reference: EA 1305). DNA sample collection for the BioResource received ethical approval from the NRES Committee South Central-Oxford (reference number: 15/SC/0388). The results of this work shall be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03062891; Results.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Distúrbios do Início e da Manutenção do Sono/terapia , Adulto , DNA/análise , Feminino , Humanos , Internet , Projetos Piloto , Projetos de Pesquisa , Inquéritos e Questionários , Terapia Assistida por Computador , Resultado do Tratamento , Adulto Jovem
11.
Dev Psychopathol ; 29(5): 1921-1933, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29162193

RESUMO

While environmental adversity has been shown to increase risk for psychopathology, individuals differ in their sensitivity to these effects. Both genes and childhood experiences are thought to influence sensitivity to the environment, and these factors may operate synergistically such that the effects of childhood experiences on later sensitivity are greater in individuals who are more genetically sensitive. In line with this hypothesis, several recent studies have reported a significant three-way interaction (Gene × Environment × Environment) between two candidate genes and childhood and adult environment on adult psychopathology. We aimed to replicate and extend these findings in a large, prospective multiwave longitudinal study using a polygenic score of environmental sensitivity and objectively measured childhood and adult material environmental quality. We found evidence for both Environment × Environment and Gene × Environment × Environment effects on psychological distress. Children with a poor-quality material environment were more sensitive to the negative effects of a poor environment as adults, reporting significantly higher psychological distress scores. These effects were further moderated by a polygenic score of environmental sensitivity. Genetically sensitive children were more vulnerable to adversity as adults, if they had experienced a poor childhood environment but were significantly less vulnerable if their childhood environment was positive. These findings are in line with the differential susceptibility hypothesis and suggest that a life course approach is necessary to elucidate the role of Gene × Environment in the development of mental illnesses.


Assuntos
Interação Gene-Ambiente , Transtornos Mentais/genética , Meio Social , Estresse Psicológico/genética , Adolescente , Adulto , Criança , Emprego , Feminino , Habitação , Humanos , Estudos Longitudinais , Masculino , Transtornos Mentais/psicologia , Pessoa de Meia-Idade , Herança Multifatorial , Estudos Prospectivos , Fatores de Risco , Classe Social , Estresse Psicológico/psicologia , Reino Unido , Adulto Jovem
12.
Am J Med Genet B Neuropsychiatr Genet ; 174(7): 701-711, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28608620

RESUMO

Emotion recognition is disrupted in many mental health disorders, which may reflect shared genetic aetiology between this trait and these disorders. We explored genetic influences on emotion recognition and the relationship between these influences and mental health phenotypes. Eight-year-old participants (n = 4,097) from the Avon Longitudinal Study of Parents and Children (ALSPAC) completed the Diagnostic Analysis of Non-Verbal Accuracy (DANVA) faces test. Genome-wide genotype data was available from the Illumina HumanHap550 Quad microarray. Genome-wide association studies were performed to assess associations with recognition of individual emotions and emotion in general. Exploratory polygenic risk scoring was performed using published genomic data for schizophrenia, bipolar disorder, depression, autism spectrum disorder, anorexia, and anxiety disorders. No individual genetic variants were identified at conventional levels of significance in any analysis although several loci were associated at a level suggestive of significance. SNP-chip heritability analyses did not identify a heritable component of variance for any phenotype. Polygenic scores were not associated with any phenotype. The effect sizes of variants influencing emotion recognition are likely to be small. Previous studies of emotion identification have yielded non-zero estimates of SNP-heritability. This discrepancy is likely due to differences in the measurement and analysis of the phenotype.


Assuntos
Emoções/fisiologia , Reconhecimento Facial/fisiologia , Marcadores Genéticos , Estudo de Associação Genômica Ampla , Herança Multifatorial , Transtornos do Neurodesenvolvimento/genética , Polimorfismo de Nucleotídeo Único , Criança , Expressão Facial , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Estudos Longitudinais , Masculino , Fenótipo , Prognóstico , Estudos Prospectivos
13.
Am J Med Genet B Neuropsychiatr Genet ; 174(2): 144-155, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27346075

RESUMO

Extinction learning is an important mechanism in the successful psychological treatment of anxiety. Individual differences in response and relapse following Cognitive Behavior Therapy may in part be explained by variability in the ease with which fears are extinguished or the vulnerability of these fears to re-emerge. Given the role of the endocannabinoid system in fear extinction, this study investigates whether genetic variation in the endocannabinoid system explains individual differences in response to CBT. Children (N = 1,309) with a primary anxiety disorder diagnosis were recruited. We investigated the relationship between variation in the CNR1, CNR2, and FAAH genes and change in primary anxiety disorder severity between pre- and post-treatment and during the follow-up period in the full sample and a subset with fear-based anxiety disorder diagnoses. Change in symptom severity during active treatment was nominally associated (P < 0.05) with two SNPs. During the follow-up period, five SNPs were nominally associated with a poorer treatment response (rs806365 [CNR1]; rs2501431 [CNR2]; rs2070956 [CNR2]; rs7769940 [CNR1]; rs2209172 [FAAH]) and one with a more favorable response (rs6928813 [CNR1]). Within the fear-based subset, the effect of rs806365 survived multiple testing corrections (P < 0.0016). We found very limited evidence for an association between variants in endocannabinoid system genes and treatment response once multiple testing corrections were applied. Larger, more homogenous cohorts are needed to allow the identification of variants of small but statistically significant effect and to estimate effect sizes for these variants with greater precision in order to determine their potential clinical utility. © 2016 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Published by Wiley Periodicals, Inc.


Assuntos
Transtornos de Ansiedade/genética , Endocanabinoides/genética , Adolescente , Amidoidrolases/genética , Amidoidrolases/metabolismo , Ansiedade/genética , Criança , Terapia Cognitivo-Comportamental/métodos , Endocanabinoides/metabolismo , Medo/psicologia , Feminino , Variação Genética/genética , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Receptor CB1 de Canabinoide/genética , Receptor CB1 de Canabinoide/metabolismo , Receptor CB2 de Canabinoide/genética , Receptor CB2 de Canabinoide/metabolismo , Resultado do Tratamento
14.
World J Biol Psychiatry ; 18(3): 215-226, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27376411

RESUMO

OBJECTIVES: Exposure-based cognitive behavioural therapy (eCBT) is an effective treatment for anxiety disorders. Response varies between individuals. Gene expression integrates genetic and environmental influences. We analysed the effect of gene expression and genetic markers separately and together on treatment response. METHODS: Adult participants (n ≤ 181) diagnosed with panic disorder or a specific phobia underwent eCBT as part of standard care. Percentage decrease in the Clinical Global Impression severity rating was assessed across treatment, and between baseline and a 6-month follow-up. Associations with treatment response were assessed using expression data from 3,233 probes, and expression profiles clustered in a data- and literature-driven manner. A total of 3,343,497 genetic variants were used to predict treatment response alone and combined in polygenic risk scores. Genotype and expression data were combined in expression quantitative trait loci (eQTL) analyses. RESULTS: Expression levels were not associated with either treatment phenotype in any analysis. A total of 1,492 eQTLs were identified with q < 0.05, but interactions between genetic variants and treatment response did not affect expression levels significantly. Genetic variants did not significantly predict treatment response alone or in polygenic risk scores. CONCLUSIONS: We assessed gene expression alone and alongside genetic variants. No associations with treatment outcome were identified. Future studies require larger sample sizes to discover associations.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Terapia Implosiva/métodos , Transtorno de Pânico/genética , Transtorno de Pânico/terapia , Transtornos Fóbicos/genética , Transtornos Fóbicos/terapia , Adulto , Feminino , Expressão Gênica , Marcadores Genéticos , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Alemanha , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Resultado do Tratamento
15.
Psychother Psychosom ; 85(3): 146-58, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27043157

RESUMO

BACKGROUND: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to cognitive behavioural therapy (CBT) in children with anxiety disorders. METHODS: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1,026 monozygotic twin pairs was examined as a function of the pairs' genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders. RESULTS: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9, 55.5 and 41.6%, respectively). CONCLUSIONS: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments but also benefit more from the most intensive types of treatment.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/métodos , Estudo de Associação Genômica Ampla , Herança Multifatorial , Poder Familiar , Criança , Feminino , Predisposição Genética para Doença , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Saúde Mental
16.
Br J Psychiatry ; 209(3): 236-43, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26989097

RESUMO

BACKGROUND: Anxiety disorders are common, and cognitive-behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. AIMS: To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). METHOD: Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. RESULTS: No variants passed a genome-wide significance threshold (P = 5 × 10(-8)) in either analysis. Four variants met criteria for suggestive significance (P<5 × 10(-6)) in association with response post-treatment, and three variants in the 6-month follow-up analysis. CONCLUSIONS: This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.


Assuntos
Transtornos de Ansiedade/genética , Terapia Cognitivo-Comportamental , Estudo de Associação Genômica Ampla , Adolescente , Transtornos de Ansiedade/terapia , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética , Resultado do Tratamento
17.
Schizophr Bull ; 42(4): 907-15, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26884548

RESUMO

There is controversy whether associations between psychosis and violence are due to coexisting substance misuse and factors increasing risk in nonpsychotic persons. Recent studies in clinical samples have implicated independent effects of paranoid delusions. Research findings suggest that individual psychotic-like-experiences on the psychosis continuum in the general population are associated with violence; it remains unclear whether this association is due to psychiatric comorbidity. We pooled data from 7 UK general population surveys (n = 23 444) and conducted a meta-analysis of individual subject data. Further meta-analyses were performed to identify heterogeneity. Main exposure variables: 5 psychotic-like-experiences and a categorical measure of psychosis. Comorbidity was established through standardized self-report instruments. Information was collected on violence, severity, victims. Paranoid ideation was associated with violence (AOR 2.26, 95% CI 1.75-2.91), severity and frequency, even when controlling for effects of other psychotic-like-experiences. Associations were not explained by comorbid conditions, including substance dependence. Psychotic disorder was associated with violence and injury to the perpetrator but associations were explained by paranoid ideation. Individual associations between hypomania, thought insertion, hallucinations, and violence were nonsignificant after adjustments, and significantly associated only when comorbid with antisocial personality disorder. Strange experiences were only associated with intimate partner violence. Paranoid ideation on a psychosis-continuum in the general population was associated with violence. All other associations were explained by comorbidity. Further investigation should determine whether paranoid ideation among persons in the community require preventive interventions, similar to those presenting to mental health services. Nevertheless, risks are considerably increased for psychotic-like-experiences with co-occurring antisocial personality disorder.


Assuntos
Transtornos Paranoides/epidemiologia , Transtornos Psicóticos/epidemiologia , Violência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Comorbidade , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Violência por Parceiro Íntimo/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Reino Unido/epidemiologia , Adulto Jovem
18.
Child Abuse Negl ; 52: 70-84, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26803688

RESUMO

Childhood maltreatment is associated with multiple adverse outcomes in adulthood including poor mental health and violence. We investigated direct and indirect pathways from childhood maltreatment to adult violence perpetration and the explanatory role of psychiatric morbidity. Analyses were based on a population survey of 2,928 young men 21-34 years in Great Britain in 2011, with boost surveys of black and minority ethnic groups and lower social grades. Respondents completed questionnaires measuring psychiatric diagnoses using standardized screening instruments, including antisocial personality disorder (ASPD), drug and alcohol dependence and psychosis. Maltreatment exposures included childhood physical abuse, neglect, witnessing domestic violence and being bullied. Adult violence outcomes included: any violence, violence toward strangers and intimate partners (IPV), victim injury and minor violence. Witnessing domestic violence showed the strongest risk for adult violence (AOR 2.70, 95% CI 2.00, 3.65) through a direct pathway, with psychotic symptoms and ASPD as partial mediators. Childhood physical abuse was associated with IPV (AOR 2.33, 95% CI 1.25, 4.35), mediated by ASPD and alcohol dependence. Neglect was associated with violence toward strangers (AOR 1.73, 95% CI 1.03, 2.91), mediated by ASPD. Prevention of violence in adulthood following childhood physical abuse and neglect requires treatment interventions for associated alcohol dependence, psychosis, and ASPD. However, witnessing family violence in childhood had strongest and direct effects on the pathway to adult violence, with important implications for primary prevention. In this context, prevention strategies should prioritize and focus on early childhood exposure to violence in the family home.


Assuntos
Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Violência/psicologia , Adolescente , Adulto , Bullying , Criança , Maus-Tratos Infantis/psicologia , Estudos Transversais , Violência Doméstica/psicologia , Exposição à Violência/psicologia , Humanos , Masculino , Estudos Retrospectivos , Reino Unido , Adulto Jovem
19.
Br J Psychiatry ; 208(2): 182-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26294368

RESUMO

BACKGROUND: We previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome. AIMS: To replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829). METHOD: Logistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed. RESULTS: There was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes. CONCLUSIONS: The association between 5HTTLPR genotype and CBT outcome did not replicate. Short-allele homozygotes showed more positive treatment outcomes, but with small, non-significant effects. Future studies would benefit from utilising whole genome approaches and large, homogenous samples.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental , Interação Gene-Ambiente , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adolescente , Alelos , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Escalas de Graduação Psiquiátrica , Indução de Remissão , Resultado do Tratamento
20.
Depress Anxiety ; 32(12): 861-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26647360

RESUMO

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). METHODS: Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). RESULTS: Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. CONCLUSIONS: Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.


Assuntos
Transtornos de Ansiedade/genética , Terapia Cognitivo-Comportamental , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Receptores de Glucocorticoides/genética , Proteínas de Ligação a Tacrolimo/genética , Adolescente , Alelos , Transtornos de Ansiedade/terapia , Criança , Pré-Escolar , Metilação de DNA/genética , Epigênese Genética/genética , Epigenômica , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Resultado do Tratamento
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