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1.
Depress Anxiety ; 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739564

RESUMO

OBJECTIVES: We aimed to examine differences in fear conditioning between anxious and nonanxious participants in a single large sample. MATERIALS AND METHODS: We employed a remote fear conditioning task (FLARe) to collect data from participants from the Twins Early Development Study (n = 1,146; 41% anxious vs. 59% nonanxious). Differences between groups were estimated for their expectancy of an aversive outcome towards a reinforced conditional stimulus (CS+) and an unreinforced conditional stimulus (CS-) during acquisition and extinction phases. RESULTS: During acquisition, the anxious group (vs. nonanxious group) showed greater expectancy towards the CS-. During extinction, the anxious group (vs. nonanxious group) showed greater expectancy to both CSs. These comparisons yielded effect size estimates (d = 0.26-0.34) similar to those identified in previous meta-analyses. CONCLUSION: The current study demonstrates that remote fear conditioning can be used to detect differences between groups of anxious and nonanxious individuals, which appear to be consistent with previous meta-analyses including in-person studies.

2.
Clin Child Fam Psychol Rev ; 24(1): 164-181, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33464448

RESUMO

In this conceptual article, we draw upon the literature regarding cognitive and behavioural factors that underpin childhood anxiety to outline how a range of these risk markers might be targeted through adventurous play. When children play in an adventurous way, climbing trees, riding their bikes fast downhill and jumping from rocks, they experience feelings of fear and excitement, thrill and adrenaline. We propose that the positive, thrilling and playful emotions associated with this type of child-led play facilitate exposure to fear-provoking situations and, in doing so, provide opportunities for children to learn about physiological arousal, uncertainty and coping. We hypothesise that these learning opportunities will, over time, reduce children's risk for elevated anxiety by increasing children's expectations and ability to cope with anxiety, decreasing intolerance of uncertainty and preventing catastrophic misinterpretations of physiological arousal. If our conceptual model is correct, then ensuring that children have the physical and psychological space required to play in an adventurous way may help to decrease their risk for elevated or clinical anxiety.

3.
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.

4.
J Behav Ther Exp Psychiatry ; 70: 101618, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33039814

RESUMO

BACKGROUND AND OBJECTIVES: Fear conditioning paradigms use various measures to assess learned fear, including autonomic arousal responses like skin conductance, and self-reports of both associative (US-expectancies) and evaluative (affective ratings) learning. The present study uses a dimensional approach to examine associations among fear indices directly. METHODS: Seventy-three participants completed a differential fear conditioning experiment, during which a neutral stimulus (CS+) was paired with an electric shock (US), while another stimulus (CS-) was never paired with the shock (partially instructed fear acquisition). Ten minutes later, both stimuli were presented without any shocks (fear extinction). Skin conductance responses and US-expectancy ratings were recorded during each phase, while self-reported negative affect was assessed for each CS at the end of extinction. RESULTS: Results showed a positive association among US-expectancy ratings and skin conductance responses during acquisition and early extinction. US-expectancy ratings during overall extinction were positively associated with post-extinction negative affect. LIMITATIONS: The lack of affective ratings post-acquisition may have obscured associations between associative and evaluative learning indices. CONCLUSIONS: Results provide evidence for the expected correspondence among different indices of associative fear learning. Findings emphasize the need for incorporating both associative and evaluative learning measures in fear conditioning paradigms.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32704198

RESUMO

This study tested the theory that anxious fathers pose a quantitatively different environmental influence on childhood anxiety than anxious mothers. The analysed sample contained 502 linked adoption units from the Early Growth and Development Study (EGDS), a longitudinal multisite study that follows 561 adopted children (57.2% boys) and their adoptive and birth parents, who were recruited through US adoption agencies. A Bayesian latent growth model predicted child anxiety symptoms between 18 months and 4.5 years from inherited (birth parent anxiety) and rearing parent anxiety. This model revealed little evidence for a difference in the influence of maternal and paternal rearing parent anxiety on child anxiety symptoms. Contrary to theoretical predictions, anxiety in the rearing father is likely to have an equivalent influence to that of the mother on both child anxiety symptoms at 18 months old and their developmental trajectory over the preschool years.

6.
Twin Res Hum Genet ; 22(6): 514-522, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31496451

RESUMO

The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent-child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.


Assuntos
Transtornos do Comportamento Infantil/epidemiologia , Desenvolvimento Infantil , Filho de Pais Incapacitados/psicologia , Doenças em Gêmeos/epidemiologia , Sistema de Registros/estatística & dados numéricos , Gêmeos/psicologia , Adolescente , Adulto , Criança , Transtornos do Comportamento Infantil/genética , Transtornos do Comportamento Infantil/psicologia , Filho de Pais Incapacitados/estatística & dados numéricos , Pré-Escolar , Doenças em Gêmeos/genética , Doenças em Gêmeos/psicologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Saúde Mental , Relações Pais-Filho , Poder Familiar/psicologia , Estudos Prospectivos , Temperamento , Gêmeos/genética , Reino Unido/epidemiologia , Adulto Jovem
7.
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
8.
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
9.
J Abnorm Child Psychol ; 47(9): 1521-1532, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30891678

RESUMO

The transition from primary to secondary school is often associated with a period of heightened anxiety and worry. For most children, any feelings of anxiety subside relatively quickly but for a small minority, emotional difficulties can continue into the first year of secondary school and beyond. This study recruited 109 children and measured their anxiety symptoms and school concerns toward the end of primary school and again at the end of their first term of secondary school. We investigated for the first time whether pre-transition measures of attentional and interpretation bias, and the magnitude of change in attentional bias toward and away from threat stimuli were associated with pre- and post-transition measures of anxiety and school concerns, and the change in these measures over time. Over 50% of the current sample exceeded clinical levels of anxiety at pre-transition. However, anxiety symptoms and school concerns had significantly reduced by post-transition. Higher levels of pre-transition anxiety or school concerns, and a greater magnitude of change in attentional bias towards threat stimuli predicted a larger reduction in anxiety symptoms and school concerns across the transition period. A greater interpretation bias toward threat was associated with higher pre-transition anxiety symptoms and school concerns but not post-transition scores, or the change in these scores. While many children experience heightened anxiety prior to school transition, this appears to be largely temporary and self-resolves. Nonetheless, the current findings highlight the importance of monitoring children's anxiety and concerns, and related cognitive processes during this important transition period.


Assuntos
Ansiedade/fisiopatologia , Viés de Atenção/fisiologia , Instituições Acadêmicas , Estudantes , Pensamento/fisiologia , Criança , Feminino , Humanos , Masculino
10.
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
11.
Mol Med ; 24(1): 7, 2018 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30134813

RESUMO

BACKGROUND: In order to retrieve episodic past events, the missing information needs to be reconstructed using information stored in semantic memory. Failures in these reconstructive processes are expressed as false memories. KIBRA single nucleotide polymorphism (rs17070145) has been linked to episodic memory performance as well as an increased risk of Alzheimer's disease and post-traumatic stress disorder (PTSD). METHODS: Here, the role of KIBRA rs17070145 polymorphism (male and female CC vs. CT/TT carriers) in reconstructive episodic memory in the Deese-Roediger-McDermott (DRM) paradigm was investigated in N = 219 healthy individuals. RESULTS: Female participants outperformed males in the free recall condition. Furthermore, a trend towards a gender x genotype interaction was found for false recognition rates. Female CT/TT carriers exhibited a lower proportion of false recognition rates for associated critical lures as compared to male CT/TT. Additionally, an association between KIBRA rs17070145 genotype, familiarity and recollection based recognition performance was found. In trials with correct recognition of listed items CT/TT carriers showed more "remember", but fewer "know" responses as compared to CC carriers. DISCUSSION AND CONCLUSION: Our findings suggest that the T-allele of KIBRA rs17070145 supports recollection based episodic memory retrieval and contributes to memory accuracy in a gender dependent manner. Findings are discussed in the context of the specific contribution of KIBRA related SNPs to reconstructive episodic memory and its implications for cognitive and emotional symptoms in dementia and PTSD.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/genética , Memória Episódica , Fosfoproteínas/genética , Adulto , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Adulto Jovem
12.
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
13.
Eur Arch Psychiatry Clin Neurosci ; 268(3): 261-268, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28364268

RESUMO

Dopamine D2 receptors (DRD2) have been strongly implicated in reward processing of natural stimuli and drugs. Using the approach-avoidance task (AAT), we recently demonstrated that smokers show an increased approach-bias toward smoking-related cues but not toward naturally rewarding stimuli. Here, we examined the contribution of the DRD2 Taq1B polymorphism to smokers' and non-smokers' responsivity toward smoking versus naturally rewarding stimuli in the AAT. Smokers carrying the minor B1 allele of the DRD2 Taq1B polymorphism showed reduced approach behavior for food-related pictures compared to non-smokers with the same allele. In the group of smokers, a higher approach-bias toward smoking-related compared to food-related pictures was found in carriers of the B1 allele. This pattern was not evident in smokers homozygous for the B2 allele. In addition, smokers with the B1 allele reported fewer attempts to quit smoking relative to smokers homozygous for the B2 allele. This is the first study demonstrating that behavioral shifts in response to smoking relative to natural rewards in smokers are mediated by the DRD2 Taq1B polymorphism. Our results indicate a reduced natural-reward brain reactivity in smokers with a genetically determined decrease in dopaminergic activity (i.e., reduction of DRD2 availability). It remains to be determined whether this pattern might be related to a different outcome after psychological cessation interventions, i.e., AAT modification paradigms, in smokers.


Assuntos
Aprendizagem da Esquiva/fisiologia , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Dopamina D2/genética , Recompensa , Fumar/genética , Adulto , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Autorrelato , Fumar/psicologia , Adulto Jovem
14.
Dev Psychol ; 54(1): 51-70, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28933890

RESUMO

A large number of studies document that children differ in the degree they are shaped by their developmental context with some being more sensitive to environmental influences than others. Multiple theories suggest that Environmental Sensitivity is a common trait predicting the response to negative as well as positive exposures. However, most research to date has relied on more or less proximal markers of Environmental Sensitivity. In this paper we introduce a new questionnaire-the Highly Sensitive Child (HSC) scale-as a promising self-report measure of Environmental Sensitivity. After describing the development of the short 12-item HSC scale for children and adolescents, we report on the psychometric properties of the scale, including confirmatory factor analysis and test-retest reliability. After considering bivariate and multivariate associations with well-established temperament and personality traits, we apply Latent Class Analysis to test for the existence of hypothesized sensitivity groups. Analyses are conducted across 5 studies featuring 4 different U.K.-based samples ranging in age from 8-19 years and with a total sample size of N = 3,581. Results suggest the 12-item HSC scale is a psychometrically robust measure that performs well in both children and adolescents. Besides being relatively independent from other common traits, the Latent Class Analysis suggests that there are 3 distinct groups with different levels of Environmental Sensitivity-low (approx. 25-35%), medium (approx. 41-47%), and high (20-35%). Finally, we provide exploratory cut-off scores for the categorization of children into these different groups which may be useful for both researchers and practitioners. (PsycINFO Database Record


Assuntos
Testes de Personalidade , Autorrelato , Temperamento , Adolescente , Criança , Meio Ambiente , Análise Fatorial , Feminino , Humanos , Inibição Psicológica , Masculino , Modelos Psicológicos , Análise Multivariada , Análise de Componente Principal , Psicologia do Adolescente , Psicologia da Criança , Psicometria , Reprodutibilidade dos Testes , Seio Sagital Superior , Adulto Jovem
15.
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
16.
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
17.
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
18.
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
19.
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
20.
J Abnorm Child Psychol ; 44(7): 1243-52, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26747448

RESUMO

This paper explores whether the increased vulnerability of children of anxious parents to develop anxiety disorders may be partially explained by these children having increased cognitive biases towards threat compared with children of non-anxious parents. Parents completed questionnaires about their child's anxiety symptoms. Children aged 5-9 (n = 85) participated in two cognitive bias tasks: 1) an emotion recognition task, and 2) an ambiguous situations questionnaire. For the emotion recognition task, there were no significant differences between at-risk children and children of non-anxious parents in their cognitive bias scores for reaction times or for accuracy in identifying angry or happy facial expressions. In addition, there were no significant differences between at-risk children and children of non-anxious parents in the number of threat interpretations made for the ambiguous situations questionnaire. It is possible that these cognitive biases only become present subsequent to the development of an anxiety disorder, or only in older at-risk children.


Assuntos
Transtornos de Ansiedade/psicologia , Cognição , Emoções , Ansiedade/psicologia , Transtornos de Ansiedade/etiologia , Criança , Pré-Escolar , Ajustamento Emocional , Feminino , Humanos , Entrevista Psicológica , Masculino , Escalas de Graduação Psiquiátrica , Fatores de Risco
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