Symptoms of major depression: Their stability, familiality, and prediction by genetic, temperamental, and childhood environmental risk factors

Background: Psychiatry has long sought to develop biological diagnostic subtypes based on symptomatic differences. This effort assumes that symptoms reflect, with good fidelity, underlying etiological processes. We address this question for major depression (MD). Methods: We examine, in twins from a population-based registry, similarity in symptom endorsement in individuals meeting criteria for last-year MD at separate interview waves and in concordant twin pairs. Among individuals with MD, we explore the impact of genetic-temperamental and child adversity risk factors on individual reported symptoms. Aggregated criteria do not separate insomnia from hypersomnia, weight gain from loss, etc. while disaggregated criteria do. Results: In twins with MD at two different waves, the mean tetrachoric correlations (+/- SEM) for aggregated and disaggregated DSM-IV A criteria were, respectively, + 0.31 +/- 0.06 and + 0.34 +/- 0.03. In monozygotic (MZ) and dizygotic (DZ) twin pairs concordant for last-year MD, the mean tetrachoric correlations for aggregated and disaggregated criteria were, respectively, + 0.33 +/- 0.07 and + 0.43 +/- 0.04, and + 0.05 +/- 0.08 and + 0.07 +/- 0.04. In individuals meeting MD criteria, neuroticism predicted the most MD symptoms (10), followed by childhood sexual abuse (8), low parental warmth (6), and genetic risk (4). Conclusions: The correlations for individual depressive symptoms over multiple episodes and within MZ twins concordant for MD are modest suggesting the important role of transient influences. The multidetermination of individual symptoms was further evidenced by their prediction by personality and exposure to early life adversities. The multiple factors influencing symptomatic presentation inMDmay contribute to our difficulties in isolating clinical depressive subtypes with distinct pathophysiologies

Developmental changes in genetic and shared environmental contributions to smoking initiation and subsequent smoking quantity in adolescence and young adulthood

Background Few studies examining the genetic architecture of cigarette smoking have focused on adolescents or examined developmental changes in additive genetic, shared environment and unique environmental influences on liability to initiate cigarette smoking and quantity of cigarettes smoked. The aim of this study is to add to the literature on liability to initiate and use cigarettes during adolescence using a nationally representative sample. Method Data for this study came from adolescent and young adult twin pairs (ages 14-33) from the National Longitudinal Study of Adolescent to Adult Health. We ran a series of developmental causal-contingent-common pathway models to examine whether additive genetic, shared and unique environmental influences on liability to the initiation of cigarette use are shared with those on smoking quantity, and whether their contributions change across development. Results We found evidence for a developmental shift in genetic and shared environmental contributions to cigarette use. Early in adolescence genetic and environmental influences work independently on liability to cigarette smoking initiation and quantity of cigarettes smoked, but liability to these behaviors becomes correlated as individuals age into young adulthood. Conclusions These findings provide insight into the causal processes underlying the liability to smoke cigarettes. With age, there is greater overlap in the genetic and environmental factors that influence the initiation of cigarette smoking and quantity of cigarettes smoked

The structure of the symptoms of major depression:Factor analysis of a lifetime worst episode of depressive symptoms in a large general population sample

Background: A range of depressive symptoms may occur during an episode of major depression (MD). Do these symptoms describe a single disorder liability or different symptom dimensions? This study investigates the structure and clinical relevance of an expanded set of depressive symptoms in a large general population sample. Methods: We studied 43,431 subjects from the Dutch Lifelines Cohort Study who participated in an online survey assessing the 9 symptom criteria of MD (DSM-IV-TR) and additional depressive symptoms during their worst lifetime episode of depressive symptoms lasting two weeks or more. Exploratory factor analyses were performed on expanded sets of 9, 14, and 24 depressive symptoms. The clinical relevance of the identified symptom dimensions was analyzed in confirmatory factor analyses including ten external validators. Results: A single dimension adequately accounted for the covariation among the 9 DSM-criteria, but multiple dimensions were needed to describe the 14 and 24 depressive symptoms. Five dimensions described the structure underlying the 24 depressive symptoms. Three cognitive affective symptom dimensions were mainly associated with risk factors for MD. Two somatic dimensions –appetite/weight problems and sleep problems—were mainly associated with BMI and age, respectively. Limitations: Respondents of our online survey tended to be more often female, older, and more highly educated than non-respondents. Conclusions: Different symptom dimensions described the structure of depressive symptoms during a lifetime worst episode in a general population sample. These symptom dimensions resembled those reported in a large clinical sample of Han-Chinese women with recurrent MD, suggesting robustness of the syndrome of MD

Cross-cultural comparison of genetic and cultural transmission of smoking initiation using an extended twin kinship model

Background: Considerable evidence from twin and adoption studies indicates that genetic and shared environmental factors play a role in the initiation of smoking behavior. Although twin and adoption designs are powerful to detect genetic and environmental influences, they do not provide information on the processes of assortative mating and parent–offspring transmission and their contribution to the variability explained by genetic and/or environmental factors. Methods: We examined the role of genetic and environmental factors in individual differences for smoking initiation (SI) using an extended kinship design. This design allows the simultaneous testing of additive and non-additive genetic, shared and individual-specific environmental factors, as well as sex differences in the expression of genes and environment in the presence of assortative mating and combined genetic and cultural transmission, while also estimating the regression of the prevalence of SI on age. A dichotomous lifetime ‘ever’ smoking measure was obtained from twins and relatives in the ‘Virginia 30,000’ sample and the ‘Australian 25,000’. Results: Results demonstrate that both genetic and environmental factors play a significant role in the liability to SI. Major influences on individual differences appeared to be additive genetic and unique environmental effects, with smaller contributions from assortative mating, shared sibling environment, twin environment, cultural transmission, and resulting genotype-environment covariance. Age regression of the prevalence of SI was significant. The finding of negative cultural transmission without dominance led us to investigate more closely two possible mechanisms for the lower parent–offspring correlations compared to the sibling and DZ twin correlations in subsets of the data: (1) age × gene interaction, and (2) social homogamy. Neither of the mechanism provided a significantly better explanation of the data. Conclusions: This study showed significant heritability, partly due to assortment, and significant effects of primarily non-parental shared environment on liability to SI

The Genetic and Environmental Sources of Resemblance Between Normative Personality and Personality Disorder Traits

Recent work has suggested a high level of congruence between normative personality, most typically represented by the big five factors, and abnormal personality traits. In 2,293 Norwegian adult twins ascertained from a population-based registry, the authors evaluated the degree of sharing of genetic and environmental influences on normative personality, assessed by the Big Five Inventory (BFI), and personality disorder traits (PDTs), assessed by the Personality Inventory for DSM-S-Norwegian Brief Form (PID-5NBF). For four of the five BFI dimensions, the strongest genetic correlation was observed with the expected PID-5-NBF dimension (e.g., neuroticism with negative affectivity [+], conscientiousness with disinhibition [-]). However, neuroticism, conscientiousness, and agreeableness had substantial genetic correlations with other PID-S-NBF dimensions (e.g., neuroticism with compulsivity [+], agreeableness with detachment [-]). Openness had no substantial genetic correlations with any PID-5-NBF dimension. The proportion of genetic risk factors shared in aggregate between the BFI traits and the PID-5-NBF dimensions was quite high for conscientiousness and neuroticism, relatively robust for extraversion and agreeableness, but quite low for openness. Of the six PID-S-NBF dimensions, three (negative affectivity, detachment, and disinhibition) shared, in aggregate, most of their genetic risk factors with normative personality traits. Genetic factors underlying psychoticism, antagonism, and compulsivity were shared to a lesser extent, suggesting that they are influenced by etiological factors not well indexed by the BFI

Genetic and Environmental Structure of DSM-IV Criteria for Antisocial Personality Disorder: A Twin Study

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40–67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct

Quantifying skip-out information loss when assessing major depression symptoms

Stress and Psychopatholog

Data mining algorithm predicts a range of adverse outcomes in major depression

Background: Course of illness in major depression (MD) is highly varied, which might lead to both under- and overtreatment if clinicians adhere to a 'one-size-fits-all' approach. Novel opportunities in data mining could lead to prediction models that can assist clinicians in treatment decisions tailored to the individual patient. This study assesses the performance of a previously developed data mining algorithm to predict future episodes of MD based on clinical information in new data. Methods: We applied a prediction model utilizing baseline clinical characteristics in subjects who reported lifetime MD to two independent test samples (total n = 4226). We assessed the model's performance to predict future episodes of MD, anxiety disorders, and disability during follow-up (1–9 years after baseline). In addition, we compared its prediction performance with well-known risk factors for a severe course of illness. Results: Our model consistently predicted future episodes of MD in both test samples (AUC 0.68–0.73, modest prediction). Equally accurately, it predicted episodes of generalized anxiety disorder, panic disorder and disability (AUC 0.65–0.78). Our model predicted these outcomes more accurately than risk factors for a severe course of illness such as family history of MD and lifetime traumas. Limitations: Prediction accuracy might be different for specific subgroups, such as hospitalized patients or patients with a different cultural background. Conclusions: Our prediction model consistently predicted a range of adverse outcomes in MD across two independent test samples derived from studies in different subpopulations, countries, using different measurement procedures. This replication study holds promise for application in clinical practice

Genetic Risks to Nicotine Dependence Predict Negative Mood and Affect in Current Non-Smokers

Nicotine is the psychoactive agent involved in nicotine dependence. However, nicotine as a drug and its effects on human psychology are largely under-investigated in genetic studies. In this study, we recruited 208 current non-smokers to evaluate the effect of nicotine and its relationship to genetic risks to nicotine dependence. Exploratory and confirmatory factor analyses, as well as measurement invariance testing, were conducted to evaluate the latent factor structures of the POMS, PANAS and DEN questionnaires across 3 nicotine doses. Structural models were used to examine the effects of nicotine and their relationship to genetic risks of nicotine dependence. We found that nicotine administration led to the change of both measurement construct and factor means, indicating the causal effect of nicotine on the psychological responses. The genotypes of rs588765 predicted the scores of the DEN Confused and Dizzy factors (p = 0.0003 and 0.001 respectively) and rs16969968 and rs588765 were associated with the PANAS Nervous factor (p = 0.006 and 0.007 respectively). Our study suggested that genetic risk of nicotine dependence is associated with acute psychological responses. The integration of psychometric analyses and dose effects could be a powerful approach for genetic study of nicotine dependence