Objective:Irritability has been proposed to underlie the developmental link between oppositional problems and depression. Little is known, however, about the genetic and environmental influences on ...irritability and its overlap with depression. Drawing on the notion of “generalist genes” (genes of general effect that underlie phenotypic overlap between disorders), the authors test the hypothesis that the association between irritability and depression is accounted for by genetic factors.
Method:Data from the G1219 study, a U.K. twin/sibling sample (N=2,651), were used in a cross-sectional and longitudinal design. The irritable and headstrong/hurtful dimensions of oppositional behavior were derived using factor analysis. Regression was used to estimate the association between depression and delinquency. Multivariate genetic analyses were used to estimate the genetic overlaps between the two components of oppositionality (irritability and headstrong/hurtful behaviors) and depression and delinquency.
Results:Irritability showed a significantly stronger phenotypic relationship with depression than with delinquency, whereas headstrong/hurtful behaviors were more strongly related to delinquency than to depression. In multivariate genetic analyses, the genetic correlation between irritability and depression (rA=0.70, 95% CI=0.59–0.82) was significantly higher than that between irritability and delinquency (rA=0.57, 95% CI=0.45–0.69); conversely, the genetic correlation between headstrong/hurtful behaviors and delinquency (rA=0.80, 95% CI=0.72–0.86) was significantly higher than that between headstrong/hurtful behaviors and depression (rA=0.46, 95% CI=0.36–0.57). In longitudinal models, the phenotypic association between irritability at wave 2 and depression at wave 3 was accounted for by the genetic association between irritability and depression at wave 2.
Conclusions:These findings are consistent with the theory that genes with general effects underlie the relationship between irritability and depression.
Diathesis‐stress models conceptualise individual differences in propensity for psychopathology as an interaction between environmental risk factors and intra‐individual vulnerabilities. In contrast, ...the differential susceptibility theory and related frameworks view intra‐individual differences as variations in sensitivity to the environments rather than merely vulnerability to them. Specifically, they suggest that more sensitive individuals are more affected by the quality of their context, whether positive or negative, than others who are less sensitive. Empirical research over the last two decades has found support for this notion in that greater sensitivity is associated with a greater risk of psychopathology in adverse contexts, but also with lower risk in positive environments. However, despite growing academic and public interest in this field, it is currently unclear to what extent the differential susceptibility model is relevant, or applicable, to clinical practice. The purpose of this review is to focus on the differential susceptibility theory as an alternative explanation of individual differences in mental health and examine its relevance in the treatment of mental health problems in young people. We provide an overview of differential susceptibility and related theories, and current relevant research in the field. We identify potential implications of differential susceptibility models for understanding and treating mental health problems in young people, whilst also highlighting important gaps in research that limit their application at present. Finally, we suggest directions for future research that will assist in the translation of differential susceptibility theories into clinical practice.
Objective:The transmission of anxiety within families is well recognized, but the underlying processes are poorly understood. Twin studies of adolescent anxiety demonstrate both genetic and ...environmental influence, and multiple aspects of parenting are associated with offspring anxiety. To date, the children-of-twins design has not been used to evaluate the relative contributions of genetic transmission compared with direct transmission of anxiety from parents to their offspring.Method:Anxiety and neuroticism measures were completed by 385 monozygotic and 486 dizygotic same-sex twin families (37% male twin pair families) from the Twin and Offspring Study in Sweden. Structural equation models tested for the presence of both genetic and environmental transmission from one generation to the next.Results:For both anxiety and neuroticism, the models provide support for significant direct environmental transmission from parents to their adolescent offspring. In contrast, there was no evidence of significant genetic transmission.Conclusions:The association between parental and offspring anxiety largely arises because of a direct association between parents and their children independent of genetic confounds. The lack of genetic transmission may reflect there being different genetic effects on these traits in adolescence and adulthood. Direct environmental transmission is in line with developmental theories of anxiety suggesting that children and adolescents learn anxious behaviors from their parents through a number of pathways such as modeling. Future analyses should combine children-of-twins data with child twin data in order to examine whether this direct effect solely represents parental influences on the offspring or whether it also includes child/adolescent anxiety evoking parental anxiety.
Background
Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture ...between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self‐, parent‐ and teacher‐rated measures in childhood and adolescence.
Methods
The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p.
Results
Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%–60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%–78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%–0.9%).
Conclusions
Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far‐reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems.
IMPORTANCE The DSM-5 classifies mood and anxiety disorders as separate conditions. However, some studies in adults find a unidimensional internalizing factor that underpins anxiety and depression, ...while others support a bidimensional model where symptoms segregate into distress (depression and generalized anxiety) and fear factors (phobia subscales). However, little is known about the phenotypic and genetic structure of internalizing psychopathology in children and adolescents. OBJECTIVE To investigate the phenotypic associations between depression and anxiety disorder symptom subscales and to test the genetic structures underlying these symptoms (DSM-5–related, unidimensional and bidimensional) across 3 developmental stages: childhood, adolescence, and early adulthood. DESIGN, SETTING, AND PARTICIPANTS Two population-based prospective longitudinal twin/sibling studies conducted in the United Kingdom. The child sample included 578 twins (mean age, approximately 8 and 10 years at waves 1 and 2, respectively). The adolescent and early adulthood sample included 2619 twins/siblings at 3 waves (mean age, 15, 17, and 20 years at each wave). MAIN OUTCOMES AND MEASURES Self-report symptoms of depression and anxiety disorders. RESULTS Phenotypically, when controlling for other anxiety subscales, depression symptoms were only associated with generalized anxiety disorder symptoms in childhood (r = 0.20-0.21); this association broadened to panic and social phobia symptoms in adolescence (r = 0.17-0.24 and r = 0.14-0.16, respectively) and all anxiety subscales in young adulthood (r = 0.06-0.19). The genetic associations were in line with phenotypic results. In childhood, anxiety subscales were influenced by a single genetic factor that did not contribute to genetic variance in depression symptoms, suggesting largely independent genetic influences on anxiety and depression. In adolescence, genetic influences were significantly shared between depression and all anxiety subscales in agreement with DSM-5 conceptualization. In young adulthood, a genetic internalizing factor influencing depression and all anxiety subscales emerged, alongside a small significant genetic fear factor. CONCLUSIONS AND RELEVANCE These results provide preliminary evidence for different phenotypic and genetic structures of internalizing disorder symptoms in childhood, adolescence, and young adulthood, with depression and anxiety becoming more associated from adolescence. The results inform molecular genetics research and transdiagnostic treatment approaches. The findings affirm the need to continue examining the classification of mood and anxiety disorders in diagnostic systems.
Background Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Although numerous ...studies have looked at genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored. Methods Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties. There were 18 pairs of MZ twins identified in which one member scored consistently higher (group mean within the clinically significant range) on self-rated depression than the other. We assessed genome-wide patterns of DNA methylation in twin buccal cell DNA using the Infinium HumanMethylation450 BeadChip from Illumina. Quality control and data preprocessing was undertaken using the wateRmelon package. Differentially methylated probes (DMPs) were identified using an analysis strategy taking into account both the significance and the magnitude of DNA methylation differences. The top differentially methylated DMP was successfully validated by bisulfite-pyrosequencing, and identified DMPs were tested in postmortem brain samples obtained from patients with major depressive disorder ( n = 14) and matched control subjects ( n = 15). Results Two reproducible depression-associated DMPs were identified, including the top-ranked DMP that was located within STK32C , which encodes a serine/threonine kinase, of unknown function. Conclusions Our data indicate that DNA methylation differences are apparent in MZ twins discordant for adolescent depression and that some of the disease-associated variation observed in buccal cell DNA is mirrored in adult brain tissue obtained from individuals with clinical depression.
Abstract
Considerable evidence supports the role of present-moment attention, a central feature of mindfulness, in subjective wellbeing maintenance and enhancement. Yet it is not clear why such a ...relation exists. This study examined the genetic and environmental contributions of present-moment attention to subjective wellbeing. Consistent with the “generalist genes hypothesis” and prior evidence, we hypothesized that presence and subjective wellbeing would show a substantial genetic correlation and smaller environmental correlation. Using a large epidemiological sample of healthy 16-year-old twins in the United Kingdom (N = 1136 monozygotic (MZ) and dizygotic (DZ) twin pairs), genetic overlap was found between presence and the cognitive component of subjective wellbeing (life satisfaction), and to a lesser extent, the affective component of subjective wellbeing (operationalized as happiness). The non-shared environmental overlap between these constructs was substantial. This study provides the first evidence known to us showing that present-centered attention, a primary component of mindfulness, has both genetic and environmental overlap with subjective wellbeing. The findings have implications for understanding mechanisms by which presence is associated with positive emotions and life satisfaction, and suggest, pending additional research, that mindfulness-based interventions to enhance wellbeing may be best suited to those with a genetic propensity toward mindful presence.
Emotional symptoms, such as anxiety and depressive symptoms, are common during adolescence, often persist over time, and can precede the emergence of severe anxiety and depressive disorders. Studies ...suggest that a vicious cycle of reciprocal influences between emotional symptoms and interpersonal difficulties may explain why some adolescents suffer from persisting emotional symptoms. However, the role of different types of interpersonal difficulties, such as social isolation and peer victimisation, in these reciprocal associations is still unclear. In addition, the lack of longitudinal twin studies conducted on emotional symptoms during adolescence means that the genetic and environmental contributions to these relationships during adolescence remain unknown.
Participants (N = 15,869) from the Twins Early Development Study completed self-reports of emotional symptoms, social isolation and peer victimisation at 12, 16 and 21 years old. A phenotypic cross-lagged model examined reciprocal associations between variables over time, and a genetic extension of this model examined the aetiology of the relationships between variables at each timepoint.
First, emotional symptoms were reciprocally and independently associated with both social isolation and peer victimisation over time, indicating that different forms of interpersonal difficulties uniquely contributed to emotional symptoms during adolescence and vice versa. Second, early peer victimisation predicted later emotional symptoms via social isolation in mid-adolescence, indicating that social isolation may constitute an intermediate pathway through which peer victimisation predicts longer-term emotional symptoms. Finally, individual differences in emotional symptoms were mostly accounted for by non-shared environmental factors at each timepoint, and both gene-environment and individual-specific environmental mechanisms were involved in the relationships between emotional symptoms and interpersonal difficulties.
Our study highlights the necessity to intervene early in adolescence to prevent the escalation of emotional symptoms over time and to consider social isolation and peer victimisation as important risk factors for the long-term persistence of emotional symptoms.
Anxiety disorders constitute the largest group of mental disorders in most western societies and are a leading cause of disability. The essential features of anxiety disorders are excessive and ...enduring fear, anxiety or avoidance of perceived threats, and can also include panic attacks. Although the neurobiology of individual anxiety disorders is largely unknown, some generalizations have been identified for most disorders, such as alterations in the limbic system, dysfunction of the hypothalamic-pituitary-adrenal axis and genetic factors. In addition, general risk factors for anxiety disorders include female sex and a family history of anxiety, although disorder-specific risk factors have also been identified. The diagnostic criteria for anxiety disorders varies for the individual disorders, but are generally similar across the two most common classification systems: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the International Classification of Diseases, Tenth Edition (ICD-10). Despite their public health significance, the vast majority of anxiety disorders remain undetected and untreated by health care systems, even in economically advanced countries. If untreated, these disorders are usually chronic with waxing and waning symptoms. Impairments associated with anxiety disorders range from limitations in role functioning to severe disabilities, such as the patient being unable to leave their home.
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