RESUMEN
Experimental paradigms measuring key psychological constructs can enhance our understanding of mechanisms underlying human psychological well-being and mental health. Delivering such paradigms remotely affords opportunities to reach larger, more representative samples than is typically possible with in-person research. The efficiency gained from remote delivery makes it easier to test replication of previously established effects in well-powered samples. There are several challenges to the successful development and delivery of remote experimental paradigms, including use of an appropriate delivery platform, identifying feasible outcome measures, and metrics of participant compliance. In this paper, we present FLARe (Fear Learning and Anxiety Response), open-source software in the form of a smartphone app and web portal for the creation and delivery of remote fear conditioning experiments. We describe the benefits and challenges associated with the creation of a remote delivery platform for fear conditioning, before presenting in detail the resultant software suite, and one instance of deploying this using the FLARe Research infrastructure. We provide examples of the application of FLARe to several research questions which illustrate the benefits of the remote approach to experiment delivery. The FLARe smartphone app and web portal are available for use by other researchers and have been designed to be user-friendly and intuitive. We hope that FLARe will be a useful tool for those interested in conducting well-powered fear conditioning studies to inform our understanding of the development and treatment of anxiety disorders.
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Aplicaciones Móviles , Humanos , Ansiedad/psicología , Miedo/psicología , Aprendizaje , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Extinción Psicológica/fisiologíaRESUMEN
BACKGROUND: This study aimed to develop, validate and compare the performance of models predicting post-treatment outcomes for depressed adults based on pre-treatment data. METHODS: Individual patient data from all six eligible randomised controlled trials were used to develop (k = 3, n = 1722) and test (k = 3, n = 918) nine models. Predictors included depressive and anxiety symptoms, social support, life events and alcohol use. Weighted sum scores were developed using coefficient weights derived from network centrality statistics (models 1-3) and factor loadings from a confirmatory factor analysis (model 4). Unweighted sum score models were tested using elastic net regularised (ENR) and ordinary least squares (OLS) regression (models 5 and 6). Individual items were then included in ENR and OLS (models 7 and 8). All models were compared to one another and to a null model (mean post-baseline Beck Depression Inventory Second Edition (BDI-II) score in the training data: model 9). Primary outcome: BDI-II scores at 3-4 months. RESULTS: Models 1-7 all outperformed the null model and model 8. Model performance was very similar across models 1-6, meaning that differential weights applied to the baseline sum scores had little impact. CONCLUSIONS: Any of the modelling techniques (models 1-7) could be used to inform prognostic predictions for depressed adults with differences in the proportions of patients reaching remission based on the predicted severity of depressive symptoms post-treatment. However, the majority of variance in prognosis remained unexplained. It may be necessary to include a broader range of biopsychosocial variables to better adjudicate between competing models, and to derive models with greater clinical utility for treatment-seeking adults with depression.
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Ansiedad , Depresión , Humanos , Adulto , Depresión/psicología , Pronóstico , Resultado del Tratamiento , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health is still being unravelled. It is important to identify which individuals are at greatest risk of worsening symptoms. This study aimed to examine changes in depression, anxiety and post-traumatic stress disorder (PTSD) symptoms using prospective and retrospective symptom change assessments, and to find and examine the effect of key risk factors. METHOD: Online questionnaires were administered to 34 465 individuals (aged 16 years or above) in April/May 2020 in the UK, recruited from existing cohorts or via social media. Around one-third (n = 12 718) of included participants had prior diagnoses of depression or anxiety and had completed pre-pandemic mental health assessments (between September 2018 and February 2020), allowing prospective investigation of symptom change. RESULTS: Prospective symptom analyses showed small decreases in depression (PHQ-9: -0.43 points) and anxiety [generalised anxiety disorder scale - 7 items (GAD)-7: -0.33 points] and increases in PTSD (PCL-6: 0.22 points). Conversely, retrospective symptom analyses demonstrated significant large increases (PHQ-9: 2.40; GAD-7 = 1.97), with 55% reported worsening mental health since the beginning of the pandemic on a global change rating. Across both prospective and retrospective measures of symptom change, worsening depression, anxiety and PTSD symptoms were associated with prior mental health diagnoses, female gender, young age and unemployed/student status. CONCLUSIONS: We highlight the effect of prior mental health diagnoses on worsening mental health during the pandemic and confirm previously reported sociodemographic risk factors. Discrepancies between prospective and retrospective measures of changes in mental health may be related to recall bias-related underestimation of prior symptom severity.
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COVID-19 , Trastornos por Estrés Postraumático , Femenino , Humanos , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/psicología , COVID-19/epidemiología , Pandemias , Depresión/psicología , Estudios Retrospectivos , Estudios Prospectivos , SARS-CoV-2 , Ansiedad/psicología , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Anxiety disorders are highly prevalent with an early age of onset. Understanding the aetiology of disorder emergence and recovery is important for establishing preventative measures and optimising treatment. Experimental approaches can serve as a useful model for disorder and recovery relevant processes. One such model is fear conditioning. We conducted a remote fear conditioning paradigm in monozygotic and dizygotic twins to determine the degree and extent of overlap between genetic and environmental influences on fear acquisition and extinction. METHODS: In total, 1937 twins aged 22-25 years, including 538 complete pairs from the Twins Early Development Study took part in a fear conditioning experiment delivered remotely via the Fear Learning and Anxiety Response (FLARe) smartphone app. In the fear acquisition phase, participants were exposed to two neutral shape stimuli, one of which was repeatedly paired with a loud aversive noise, while the other was never paired with anything aversive. In the extinction phase, the shapes were repeatedly presented again, this time without the aversive noise. Outcomes were participant ratings of how much they expected the aversive noise to occur when they saw either shape, throughout each phase. RESULTS: Twin analyses indicated a significant contribution of genetic effects to the initial acquisition and consolidation of fear, and the extinction of fear (15, 30 and 15%, respectively) with the remainder of variance due to the non-shared environment. Multivariate analyses revealed that the development of fear and fear extinction show moderate genetic overlap (genetic correlations 0.4-0.5). CONCLUSIONS: Fear acquisition and extinction are heritable, and share some, but not all of the same genetic influences.
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Extinción Psicológica , Miedo , Humanos , Miedo/fisiología , Extinción Psicológica/fisiología , Condicionamiento Clásico/fisiología , Ansiedad , Gemelos Dicigóticos/genéticaRESUMEN
AIMS: To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care. METHODS: Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3-4, 6-8,
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Antidepresivos , Depresión , Adulto , Antidepresivos/uso terapéutico , Ansiedad , Depresión/diagnóstico , Depresión/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estado Civil , PronósticoRESUMEN
BACKGROUND: Anxiety sensitivity, the tendency to fear the symptoms of anxiety, is a key risk factor for the development anxiety disorders. Although obsessive-compulsive disorder was previously classified as an anxiety disorder, the prospective relationship between anxiety sensitivity and obsessive-compulsive symptoms (OCS) has been largely overlooked. Furthermore, a lack of genetically informative studies means the aetiology of the link between anxiety sensitivity and OCS remains unclear. METHODS: Adolescent twins and siblings (N = 1,579) from the G1219 study completed self-report questionnaires two years apart assessing anxiety sensitivity, OCS, anxiety and depression. Linear regression models tested prospective associations between anxiety sensitivity and OCS, with and without adjustment for anxiety and depressive symptoms. A phenotypic cross-lagged model assessed bidirectional influences between anxiety sensitivity and OCS over time, and a genetic version of this model examined the aetiology of these associations. RESULTS: Anxiety sensitivity was prospectively associated with changes in OCS, even after controlling for comorbid anxiety and depressive symptoms. The longitudinal relationship between anxiety sensitivity and OCS was bidirectional, and these associations were predominantly accounted for by nonshared environmental influences. CONCLUSIONS: Our findings are consistent with the notion that anxiety sensitivity is a risk factor for OCS during adolescence, but also suggest that experiencing OCS confers risk for heightened anxiety sensitivity. The reciprocal links between OCS and anxiety sensitivity over time are likely to be largely mediated by nonshared environmental experiences, as opposed to common genes. Our findings raise the possibility that interventions aimed at ameliorating anxiety sensitivity could reduce risk for OCS, and vice versa.
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Ansiedad/genética , Susceptibilidad a Enfermedades , Ambiente , Trastorno Obsesivo Compulsivo/genética , Gemelos/genética , Gemelos/psicología , Adolescente , Ansiedad/epidemiología , Niño , Comorbilidad , Humanos , Estudios Longitudinales , Trastorno Obsesivo Compulsivo/epidemiología , Hermanos/psicología , Adulto JovenRESUMEN
Genome-wide studies often exclude family members, even though they are a valuable source of information. We identified parent-offspring pairs, siblings and couples in the UK Biobank and implemented a family-based DNA-derived heritability method to capture additional genetic effects and multiple sources of environmental influence on neuroticism and years of education. Compared to estimates from unrelated individuals, total heritability increased from 10 to 27% and from 17 to 56% for neuroticism and education respectively by including family-based genetic effects. We detected no family environmental influences on neuroticism. The couple similarity variance component explained 35% of the variation in years of education, probably reflecting assortative mating. Overall, our genetic and environmental estimates closely replicate previous findings from an independent sample. However, more research is required to dissect contributions to the additional heritability by rare and structural genetic effects, assortative mating, and residual environmental confounding. The latter is especially relevant for years of education, a highly socially contingent variable, for which our heritability estimate is at the upper end of twin estimates in the literature. Family-based genetic effects could be harnessed to improve polygenic prediction.
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Educación/tendencias , Neuroticismo/fisiología , Adulto , Anciano , Bancos de Muestras Biológicas , Ambiente , Familia , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Herencia Multifactorial , Linaje , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Hermanos , Gemelos , Reino UnidoRESUMEN
Fear conditioning models key processes related to the development, maintenance and treatment of anxiety disorders and is associated with group differences in anxiety. However, laboratory administration of tasks is time and cost intensive, precluding assessment in large samplesnecessary for the analysis of individual differences. This study introduces a newly developed smartphone app that delivers a fear conditioning paradigm remotely using a loud human scream as an aversive stimulus. Three groups of participants (total nâ¯=â¯152) took part in three studies involving a differential fear conditioning experiment to assess the reliability and validity of a smartphone administered fear conditioning paradigm. This comprised of fear acquisition, generalisation, extinction, and renewal phases during which online US-expectancy ratings were collected during every trial with evaluative ratings of negative affect at three time points. We show that smartphone app delivery of a fear conditioning paradigm results in a pattern of fear learning comparable to traditional laboratory delivery and is able to detect individual differences in performance that show comparable associations with anxiety to the prior group differences literature.
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Condicionamiento Clásico , Miedo , Aplicaciones Móviles/estadística & datos numéricos , Teléfono Inteligente , Estimulación Acústica , Adulto , Afecto , Ansiedad/psicología , Extinción Psicológica , Femenino , Generalización Psicológica , Humanos , Individualidad , Masculino , Estimulación Luminosa , Reproducibilidad de los Resultados , Factores de Tiempo , Adulto JovenRESUMEN
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural-geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
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Envejecimiento/genética , Estatura/genética , Índice de Masa Corporal , Bases de Datos Factuales , Interacción Gen-Ambiente , Gemelos Dicigóticos/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores SocioeconómicosRESUMEN
BACKGROUND: Punitive parenting and stressful life events are associated with obsessive-compulsive symptoms (OCS). However, the lack of longitudinal, genetically-informative studies means it remains unclear whether these factors represent environmentally-mediated risks for the development of OCS. METHODS: Twins and siblings from the Genesis1219 study completed self-report questionnaires two years apart (Time 1: N = 2616, mean age = 15.0; Time 2: N = 1579, mean age = 17.0 years) assessing OCS, maternal and paternal punitive parenting, and dependent stressful life events. Multiple regression models tested cross-sectional and longitudinal associations between the putative environmental risk factors and obsessive-compulsive symptoms using: (a) individual scores; and (b) monozygotic twin difference scores. The aetiologies of significant phenotypic associations between putative risk factors and OCS were further examined using multivariate genetic models. RESULTS: At a phenotypic level, maternal and paternal punitive parenting and stressful life events were all associated with OCS both cross-sectionally and longitudinally. However, only stressful life events predicted the subsequent development of OCS, after controlling for earlier symptoms. Genetic models indicated that the association between life events and change in OCS symptoms was due to both genetic (48%) and environmental (52%) influences. Overall, life events associated with change in OCS accounted for 1.2% of variation in OCS at Time 2. CONCLUSIONS: Stressful life events, but not punitive parenting, predict OCS change during adolescence at a phenotypic level. This association exists above and beyond genetic confounding, consistent with the hypothesis that stressful life events play a causal role in the development of obsessive-compulsive symptoms.
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Enfermedades en Gemelos/epidemiología , Trastorno Obsesivo Compulsivo/epidemiología , Hermanos/psicología , Estrés Psicológico/epidemiología , Gemelos/estadística & datos numéricos , Adolescente , Adulto , Comorbilidad , Estudios Transversales , Enfermedades en Gemelos/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastorno Obsesivo Compulsivo/psicología , Responsabilidad Parental , Factores de Riesgo , Autoinforme , Estrés Psicológico/psicología , Encuestas y Cuestionarios , Gemelos/psicologíaRESUMEN
BACKGROUND: Associations between parenting and child outcomes are often interpreted as reflecting causal, social influences. However, such associations may be confounded by genes common to children and their biological parents. To the extent that these shared genes influence behaviours in both generations, a passive genetic mechanism may explain links between them. Here we aim to quantify the relative importance of passive genetic v. social mechanisms in the intergenerational association between parent-offspring relationship quality and offspring internalizing problems in adolescence. METHODS: We used a Children-of-Twins (CoT) design with data from the parent-based Twin and Offspring Study of Sweden (TOSS) sample [909 adult twin pairs and their offspring; offspring mean age 15.75 (2.42) years], and the child-based Swedish Twin Study of CHild and Adolescent Development (TCHAD) sample [1120 adolescent twin pairs; mean age 13.67 (0.47) years]. A composite of parent-report measures (closeness, conflict, disagreements, expressions of affection) indexed parent-offspring relationship quality in TOSS, and offspring self-reported internalizing symptoms were assessed using the Child Behavior Checklist (CBCL) in both samples. RESULTS: A social transmission mechanism explained the intergenerational association [r = 0.21 (0.16-0.25)] in our best-fitting model. A passive genetic transmission pathway was not found to be significant, indicating that parental genetic influences on parent-offspring relationship quality and offspring genetic influences on their internalizing problems were non-overlapping. CONCLUSION: These results indicate that this intergenerational association is a product of social interactions between children and parents, within which bidirectional effects are highly plausible. Results from genetically informative studies of parenting-related effects should be used to help refine early parenting interventions aimed at reducing risk for psychopathology.
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Interacción Gen-Ambiente , Genética Conductual , Relaciones Padres-Hijo , Padres/psicología , Gemelos/psicología , Adolescente , Adulto , Hijo de Padres Discapacitados/psicología , Hijo de Padres Discapacitados/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Psicopatología , Autoinforme , SueciaRESUMEN
Although gene-environment correlation is recognized and investigated by family studies and recently by SNP-heritability studies, the possibility that genetic effects on traits capture environmental risk factors or protective factors has been neglected by polygenic prediction models. We investigated covariation between trait-associated polygenic variation identified by genome-wide association studies (GWASs) and specific environmental exposures, controlling for overall genetic relatedness using a genomic relatedness matrix restricted maximum-likelihood model. In a UK-representative sample (n = 6,710), we find widespread covariation between offspring trait-associated polygenic variation and parental behavior and characteristics relevant to children's developmental outcomes-independently of population stratification. For instance, offspring genetic risk for schizophrenia was associated with paternal age (R2 = 0.002; P = 1e-04), and offspring education-associated variation was associated with variance in breastfeeding (R2 = 0.021; P = 7e-30), maternal smoking during pregnancy (R2 = 0.008; P = 5e-13), parental smacking (R2 = 0.01; P = 4e-15), household income (R2 = 0.032; P = 1e-22), watching television (R2 = 0.034; P = 5e-47), and maternal education (R2 = 0.065; P = 3e-96). Education-associated polygenic variation also captured covariation between environmental exposures and children's inattention/hyperactivity, conduct problems, and educational achievement. The finding that genetic variation identified by trait GWASs partially captures environmental risk factors or protective factors has direct implications for risk prediction models and the interpretation of GWAS findings.
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Exposición a Riesgos Ambientales , Herencia Multifactorial , Polimorfismo de Nucleótido Simple , Adulto , Niño , Interacción Gen-Ambiente , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Factores de RiesgoRESUMEN
Exposure-based psychological treatments for anxiety have high efficacy. However, a substantial proportion of patients do not respond to therapy. Research examining the potential biological underpinnings of therapy response is still in its infancy, and most studies have focussed on candidate genes. To our knowledge, this study represents the first investigation of genome-wide expression profiles with respect to treatment outcome. Participants (n=102) with panic disorder or specific phobia received exposure-based cognitive behavioural therapy. Treatment outcome was defined as percentage reduction from baseline in clinician-rated severity of their primary anxiety diagnosis at post treatment and 6 month follow-up. Gene expression was determined from whole blood samples at three time points using the Illumina HT-12v4 BeadChip microarray. Linear regression models tested the association between treatment outcome and changes in gene expression from pre-treatment to post treatment, and pre-treatment to follow-up. Network analysis was conducted using weighted gene co-expression network analysis, and change in the detected modules from pre-treatment to post treatment and follow-up was tested for association with treatment outcome. No changes in gene expression were significantly associated with treatment outcomes when correcting for multiple testing (q<0.05), although a small number of genes showed a suggestive association with treatment outcome (q<0.5, n=20). Network analysis showed no association between treatment outcome and change in gene expression for any module. We report suggestive evidence for the role of a small number of genes in treatment outcome. Although preliminary, these findings contribute to a growing body of research suggesting that response to psychological therapies may be associated with changes at a biological level.
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Trastornos de Ansiedad/genética , Trastornos de Ansiedad/terapia , Terapia Implosiva , Transcriptoma , Adulto , Anciano , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research.
RESUMEN
BACKGROUND: Maladaptive cognitive biases such as negative attributional style and hopelessness have been implicated in the development and maintenance of depression. According to the hopelessness theory of depression, hopelessness mediates the association between attributional style and depression. The aetiological processes underpinning this influential theory remain unknown. The current study investigated genetic and environmental influences on hopelessness and its concurrent and longitudinal associations with attributional style and depression across adolescence and emerging adulthood. Furthermore, given high co-morbidity between depression and anxiety, the study investigated whether these maladaptive cognitions constitute transdiagnostic cognitive content common to both internalizing symptoms. METHOD: A total of 2619 twins/siblings reported attributional style (mean age 15 and 17 years), hopelessness (mean age 17 years), and depression and anxiety symptoms (mean age 17 and 20 years). RESULTS: Partial correlations revealed that attributional style and hopelessness were uniquely associated with depression but not anxiety symptoms. Hopelessness partially mediated the relationship between attributional style and depression. Hopelessness was moderately heritable (A = 0.37, 95% confidence interval 0.28-0.47), with remaining variance accounted for by non-shared environmental influences. Independent pathway models indicated that a set of common genetic influences largely accounted for the association between attributional style, hopelessness and depression symptoms, both concurrently and across development. CONCLUSIONS: The results provide novel evidence that associations between attributional style, hopelessness and depression symptoms are largely due to shared genetic liability, suggesting developmentally stable biological pathways underpinning the hopelessness theory of depression. Both attributional style and hopelessness constituted unique cognitive content in depression. The results inform molecular genetics research and cognitive treatment approaches.
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Ansiedad , Depresión , Esperanza , Pesimismo , Hermanos , Adolescente , Adulto , Ansiedad/epidemiología , Ansiedad/etiología , Ansiedad/genética , Ansiedad/psicología , Depresión/epidemiología , Depresión/etiología , Depresión/genética , Depresión/psicología , Femenino , Humanos , Londres/epidemiología , Estudios Longitudinales , Masculino , Hermanos/psicología , Adulto JovenRESUMEN
BACKGROUND: Depression and anxiety persist within and across diagnostic boundaries. The manner in which common v. disorder-specific genetic and environmental influences operate across development to maintain internalizing disorders and their co-morbidity is unclear. This paper investigates the stability and change of etiological influences on depression, panic, generalized, separation and social anxiety symptoms, and their co-occurrence, across adolescence and young adulthood. METHOD: A total of 2619 twins/siblings prospectively reported symptoms of depression and anxiety at mean ages 15, 17 and 20 years. RESULTS: Each symptom scale showed a similar pattern of moderate continuity across development, largely underpinned by genetic stability. New genetic influences contributing to change in the developmental course of the symptoms emerged at each time point. All symptom scales correlated moderately with one another over time. Genetic influences, both stable and time-specific, overlapped considerably between the scales. Non-shared environmental influences were largely time- and symptom-specific, but some contributed moderately to the stability of depression and anxiety symptom scales. These stable, longitudinal environmental influences were highly correlated between the symptoms. CONCLUSIONS: The results highlight both stable and dynamic etiology of depression and anxiety symptom scales. They provide preliminary evidence that stable as well as newly emerging genes contribute to the co-morbidity between depression and anxiety across adolescence and young adulthood. Conversely, environmental influences are largely time-specific and contribute to change in symptoms over time. The results inform molecular genetics research and transdiagnostic treatment and prevention approaches.
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Trastornos de Ansiedad/etiología , Trastorno Depresivo/etiología , Interacción Gen-Ambiente , Adolescente , Adulto , Trastornos de Ansiedad/genética , Ansiedad de Separación/etiología , Ansiedad de Separación/genética , Trastorno Depresivo/genética , Femenino , Humanos , Masculino , Trastorno de Pánico/etiología , Trastorno de Pánico/genética , Trastornos Fóbicos/etiología , Trastornos Fóbicos/genética , Hermanos , Adulto JovenRESUMEN
BACKGROUND: Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. METHOD: We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. RESULTS: Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. CONCLUSIONS: We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.
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Hijo de Padres Discapacitados/psicología , Trastorno Depresivo/psicología , Control Interno-Externo , Relaciones Padres-Hijo , Padres/psicología , Adolescente , Adopción , Adulto , Niño , Hijo de Padres Discapacitados/estadística & datos numéricos , Estudios Transversales , Trastorno Depresivo/genética , Femenino , Predisposición Genética a la Enfermedad/genética , Predisposición Genética a la Enfermedad/psicología , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Psicopatología , Autoinforme , Suecia , Gemelos/psicología , Estados Unidos , Adulto JovenRESUMEN
BACKGROUND: Little is known about the factors influencing the stability of obsessive-compulsive behaviour (OCB) from childhood to adolescence. The current study aimed to investigate: (1) the stability of paediatric OCB over a 12-year period; (2) the extent to which genetic and environmental factors influence stability; and (3) the extent to which these influences are stable or dynamic across development. METHOD: The sample included 14 743 twins from a population-based study. Parental ratings of severity of OCB were collected at ages 4, 7, 9 and 16 years. RESULTS: OCB was found to be moderately stable over time. The genetic influence on OCB at each age was moderate, with significant effects also of non-shared environment. Genetic factors exerted a substantial influence on OCB persistence, explaining 59-80% of the stability over time. The results indicated genetic continuity, whereby genetic influences at each age continue to affect the expression of OCB at subsequent ages. However, we also found evidence for genetic attenuation in that genetic influences at one age decline in their influence over time, and genetic innovation whereby new genes 'come on line' at each age. Non-shared environment influenced stability of OCB to a lesser extent and effects were largely unique to each age and displayed negligible influences on OCB at later time points. CONCLUSIONS: OCB appears to be moderately stable across development, and stability is largely driven by genetic factors. However, the genetic effects are not entirely constant, but rather the genetic influence on OCB appears to be a developmentally dynamic process.
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Desarrollo del Adolescente/fisiología , Desarrollo Infantil/fisiología , Enfermedades en Gemelos/genética , Trastorno Obsesivo Compulsivo/genética , Adolescente , Niño , Preescolar , Enfermedades en Gemelos/epidemiología , Enfermedades en Gemelos/etiología , Inglaterra/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastorno Obsesivo Compulsivo/epidemiología , Trastorno Obsesivo Compulsivo/etiología , Índice de Severidad de la Enfermedad , Gales/epidemiologíaRESUMEN
Anxiety disorders that are the most commonly occurring psychiatric disorders in childhood, are associated with a range of social and educational impairments and often continue into adulthood. Cognitive behaviour therapy (CBT) is an effective treatment option for the majority of cases, although up to 35-45% of children do not achieve remission. Recent research suggests that some genetic variants may be associated with a more beneficial response to psychological therapy. Epigenetic mechanisms such as DNA methylation work at the interface between genetic and environmental influences. Furthermore, epigenetic alterations at the serotonin transporter (SERT) promoter region have been associated with environmental influences such as stressful life experiences. In this study, we measured DNA methylation upstream of SERT in 116 children with an anxiety disorder, before and after receiving CBT. Change during treatment in percentage DNA methylation was significantly different in treatment responders vs nonresponders. This effect was driven by one CpG site in particular, at which responders increased in methylation, whereas nonresponders showed a decrease in DNA methylation. This is the first study to demonstrate differences in SERT methylation change in association with response to a purely psychological therapy. These findings confirm that biological changes occur alongside changes in symptomatology following a psychological therapy such as CBT.
Asunto(s)
Trastornos de Ansiedad/genética , Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual , Metilación de ADN/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Adolescente , Niño , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: The classification of anxiety and depressive disorders has long been debated and has important clinical implications. The present study combined a genetically sensitive design and multiple time points to investigate cognitive content specificity in anxiety and depressive disorder symptoms across anxiety sensitivity dimensions, a cognitive distortion implicated in both disorders. METHOD: Phenotypic and genetic correlations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were examined at five waves of data collection within childhood, adolescence and early adulthood in two representative twin studies (n pairs = 300 and 1372). RESULTS: The physical concerns dimension of anxiety sensitivity (fear of bodily symptoms) was significantly associated with anxiety but not depression at all waves. Genetic influences on physical concerns overlapped substantially more with anxiety than depression. Conversely, mental concerns (worry regarding cognitive control) were phenotypically more strongly associated with depression than anxiety. Social concerns (fear of publicly observable symptoms of anxiety) were associated with both anxiety and depression in adolescence. Genetic influences on mental and social concerns were shared to a similar extent with both anxiety and depression. CONCLUSIONS: Phenotypic patterns of cognitive specificity and broader genetic associations between anxiety sensitivity dimensions, anxiety and depressive disorder symptoms were similar at all waves. Both disorder-specific and shared cognitive concerns were identified, suggesting it is appropriate to classify anxiety and depression as distinct but related disorders and confirming the clinical perspective that cognitive therapy is most likely to benefit by targeting cognitive concerns relating specifically to the individual's presenting symptoms across development.