We derived and tested a short form of the Center for Epidemiologic Studies Depression Scale (CES-D) for reliability and validity among a sample of well older adults in a large Health Maintenance Organization. The 10-item screening questionnaire, the CESD-10, showed good predictive accuracy when compared to the full-length 20-item version of the CES-D (kappa =.97, P <.001). Cutoff scores for depressive symptoms were > or = 16 for the full-length questionnaire and > or = 10 for the 10-item version. We discuss other potential cutoff values. The CESD-10 showed an expected positive correlation with poorer health status scores (r =.37) and a strong negative correlation with positive affect (r = -.63). Retest correlations for the CESD-10 were comparable to those in other studies (r =.71). We administered the CESD-10 again after 12 months, and scores were stable with strong correlation of r =.59.

We aimed to investigate the rates of positive screening for depression, anxiety, stress, and suicide risk in adults with seizures [i.e., well-matched groups of patients with focal epilepsy vs. idiopathic generalized epilepsy (IGE) vs. functional seizures (FS)].This was a cross sectional study. Patients, 19-55 years of age, with a diagnosis of IGE, focal epilepsy or FS were investigated at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from September 2022 until January 2023 and during their follow-up visits. We used the validated Farsi version of DASS-21 (Depression-Anxiety-Stress Scale) to investigate and screen for depression, anxiety, and stress in these patients. We also used the Beck Scale for Suicide Ideation (BSSI).Forty patients with focal epilepsy, 40 persons with IGE, and 40 individuals with FS were included. Depression and anxiety were more prevalent among patients with FS compared with those with epilepsy. The rate of stress among patients with FS was not significantly different compared with that in patients with epilepsy. The suicide risks were not significantly different between the groups either.Patients with FS are at high risk for psychiatric comorbidities that is comparable or even worse than that in patients with epilepsy. Specific validated scales to screen for psychiatric comorbidities and suicide risk should be integral components of the evaluation and treatment of all patients with seizures.© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.

The present study investigated a possible interaction between a functional polymorphism in the MAOA gene promoter (MAOA-VNTR) and childhood maltreatment in the prediction of adolescent male and female delinquency. A cohort of 1,825 high school students, 17-18 years old, completed an anonymous questionnaire during class hours which included questions on childhood maltreatment, sexual abuse, and delinquency. Saliva samples were collected for DNA isolation, and analyzed for the MAOA-VNTR polymorphism. Self-reported maltreatment was a strong risk factor for adolescent delinquent behavior. The MAOA genotype also showed a significant main effect when controlled for maltreatment. Boys with a short variant and girls with one or two long variants of the polymorphism showed a higher risk for delinquency when exposed to maltreatment. Our results confirm previous findings of an interaction between the MAOA-VNTR polymorphism and self-reported maltreatment. Results for boys and girls differ according to MAOA-VNTR genotype and direction of phenotypic expression.

The efficacy of interventions might be underestimated or even go undetected as a main effect when it is hidden in gene-by-environment (G×E) interactions. This review moves beyond the problems thwarting correlational G×E research to propose genetic differential susceptibility experiments. G×E experiments can test the bright side as well as the dark side of the moderating role of genotypes traditionally considered to represent vulnerability to negative conditions. The differential susceptibility model predicts that carriers of these risk genotypes profit most from interventions changing the environment for the better. The evolutionary background of G×E and differential susceptibility is discussed, and statistical methods for the analysis of differential susceptibility (versus diathesis stress) are reviewed. Then, based on results from 22 randomized G×E experiments, meta-analytic evidence for the differential susceptibility model is presented. Intervention effects are much stronger in the susceptible genotypes than in the nonsusceptible genotypes. The final sections suggest possibilities to broaden the G component in the G×E equation by including genetic pathways, and to broaden the E component by including methylation level and gene expression as promising ways to probe the concept of the environment more deeply and address the perennial issue of what works for whom.

This study investigated young adolescents' perceptions of their peers' prosocial behaviours. In eight focus groups, 53 11- to 13-year olds described specific prosocial acts of their peers. Results suggest that traditional research has not addressed the diversity of prosocial behaviours that youth enact, nor emphasized behaviours that are salient to young adolescents. Such behaviours included standing up for others, encouraging others, helping others develop skills, including others who are left out, and being humorous. Facilitating emotional regulation of others emerged as an important component of prosocial behaviour. These data can help guide future research on prosocial development to include a broader array of authentic behaviours of young adolescents.

Previously, sequence variation in the glucocorticoid (GR) and mineralocorticoid (MR) receptor genes (NR3C1 and NR3C2, respectively) have been found to be associated with physiological stress responses to social stress tests in small samples of adult men and oral contraceptives (OC) using women. Associations between single nucleotide polymorphisms (SNPs) in the GR (23EK-rs6190, 9beta-rs6198, BclI-rs4142324) and the MR gene (I180V-rs5522 and -2G/C (rs2070951) with cortisol and heart rate responses to a performance-related social stress task (public speaking and mental arithmetic) were examined in a large sample (n = 553) of adolescents (15-17 years). To make comparisons with previous findings, associations were tested in boys (n = 277), free-cycling (FC) girls (n = 183) and OC users (n = 93). None of the previously reported associations in adults could be replicated in this large adolescent sample. Explanations for non-replication are discussed.

Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effects on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller hippocampal and anterior cingulate volumes, increased amygdala function, and decreased medial prefrontal/anterior cingulate function. In addition, patients with PTSD show increased cortisol and norepinephrine responses to stress. Treatments that are efficacious for PTSD show a promotion of neurogenesis in animal studies, as well as promotion of memory and increased hippocampal volume in PTSD.

This study examined adolescents' feelings of being caught between parents to see whether this construct helps to explain (1) variability in their postdivorce adjustment and (2) associations between family/child characteristics and adolescent adjustment. Adolescents 10 to 18 years old (N = 522) were interviewed by telephone 4 1/2 years after their parents' separation. Feeling caught between parents was related to high parental conflict and hostility and low parental cooperation. Being close to both parents was associated with low feelings of being caught. The relation between time spent with each parent and feeling caught depended on the coparenting relationship. Adolescents in dual residence were especially likely to feel caught when parents were in high conflict, and especially unlikely to feel caught when parents cooperated. Feeling caught was related to poor adjustment outcomes. Parental conflict was only related to adjustment outcomes indirectly, through adolescents' feelings of being caught.

Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (h) estimates were ~10%, and both traits were highly genetically correlated (LDSC r> 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.

We summarized peer-reviewed literature on aggressive episodes perpetrated by adult patients admitted to general hospital units, especially psychiatry or emergency services. We examined the main factors associated with aggressive behaviors in the hospital setting, with a special focus on the European experience.A number of variables, including individual, historical, and contextual variables, are significant risk factors for aggression among hospitalized people. Drug abuse can be considered a trans-dimensional variable which deserves particular attention. Although mental health disorders represent a significant component in the risk of aggression, there are many factors including drug abuse, past history of physically aggressive behavior, childhood abuse, social and cultural patterns, relational factors, and contextual variables that can increase the risk of overt aggressive behavior in the general hospital. This review highlights the need to undertake initiatives aimed to enhance understanding, prevention, and management of violence in general hospital settings across Europe.

<p>Third-party punishment (TPP) plays an important role in both improving cooperation and maintaining social norms. However, Cognitive Evaluation Theory suggests that TPP may also negatively affect cooperation, because TPP reduces the internal motivation of cooperative behaviors. Therefore, the influence of TPP on cooperation may have two different manifestations depending on the specific kind of activated social norms &mdash; descriptive norms (what most people actually do) or injunctive norms (what people should do). This study used two experiments to examine the influence of TPP on cooperation. Experiment 1 analyzed the effects of the two different social norms on cooperation without TPP. The subjects (120 university students) participated in a two-round Dictator Game, which used a 2 (high/low descriptive norms) by 2 (high/low injunctive norms) between-subjects design. Experiment 2 (with 300 university students) examined the influence of different TPP frequencies on cooperation. The subjects participated in a four-round Dictator Game with a third-party member who could punish both the dictator and the receiver in Round 2 and 3. In Round 3, the subjects were informed the frequency of TPP (a between-subjects factor), which were controlled by the experimenter on 10 levels ranging from 0% to 90%. The result showed that descriptive norms had a more significant influence in comparison to injunctive norms, and there was a significant interaction between the two types of norms. Descriptive norms played a more important role on cooperation when there was no punisher, whereas injunctive norms' effect on cooperation was stronger when there was a punisher. The results also implied that a low frequency of TPP could successfully increase the level of cooperation, even when the punishment sanction was removed. We also found that higher frequency of TPP reduced the internal motivation on cooperation. An explanation of these effects was that TPP could not only remind subjects of the injunctive norms but also the existence of norm violation. When the perception of norm violation increased with higher frequency of TPP, the perception of descriptive norms decreases and so do cooperative behaviors.</p>

Social initiative and behavioral control represent two major dimensions of children's social competence. Cultural norms and values with respect to these dimensions may affect the exhibition, meaning, and development of specific social behaviors such as sociability, shyness-inhibition, cooperation-compliance, and aggression-defiance, as well as the quality and function of social relationships. The culturally guided social interaction processes including evaluations and responses likely serve as an important mediator of cultural influence on children's social behaviors, relationships, and developmental patterns. In this article, we review research on children's social functioning and peer relationships in different cultures from an integrative contextual-developmental perspective. We also review research on the implications of the macro-level social and cultural changes that are happening in many societies for socialization and development of social competence.

In this investigation, gene-environment interaction effects in predicting resilience in adaptive functioning among maltreated and nonmaltreated low-income children (N = 595) were examined. A multicomponent index of resilient functioning was derived and levels of resilient functioning were identified. Variants in four genes (serotonin transporter linked polymorphic region, corticotropin releasing hormone receptor 1, dopamine receptor D4-521C/T, and oxytocin receptor) were investigated. In a series of analyses of covariance, child maltreatment demonstrated a strong negative main effect on children's resilient functioning, whereas no main effects for any of the genotypes of the respective genes were found. However, gene-environment interactions involving genotypes of each of the respective genes and maltreatment status were obtained. For each respective gene, among children with a specific genotype, the relative advantage in resilient functioning of nonmaltreated compared to maltreated children was stronger than was the case for nonmaltreated and maltreated children with other genotypes of the respective gene. Across the four genes, a composite of the genotypes that more strongly differentiated resilient functioning between nonmaltreated and maltreated children provided further evidence of genetic variations influencing resilient functioning in nonmaltreated children, whereas genetic variation had a negligible effect on promoting resilience among maltreated children. Additional effects were observed for children based on the number of subtypes of maltreatment children experienced, as well as for abuse and neglect subgroups. Finally, maltreated and nonmaltreated children with high levels of resilience differed in their average number of differentiating genotypes. These results suggest that differential resilient outcomes are based on the interaction between genes and developmental experiences.

Gene-by-environment interaction (G×E) studies in psychiatry have typically been conducted using a candidate G×E (cG×E) approach, analogous to the candidate gene association approach used to test genetic main effects. Such cG×E research has received widespread attention and acclaim, yet cG×E findings remain controversial. The authors examined whether the many positive cG×E findings reported in the psychiatric literature were robust or if, in aggregate, cG×E findings were consistent with the existence of publication bias, low statistical power, and a high false discovery rate.The authors conducted analyses on data extracted from all published studies (103 studies) from the first decade (2000-2009) of cG×E research in psychiatry.Ninety-six percent of novel cG×E studies were significant compared with 27% of replication attempts. These findings are consistent with the existence of publication bias among novel cG×E studies, making cG×E hypotheses appear more robust than they actually are. There also appears to be publication bias among replication attempts because positive replication attempts had smaller average sample sizes than negative ones. Power calculations using observed sample sizes suggest that cG×E studies are underpowered. Low power along with the likely low prior probability of a given cG×E hypothesis being true suggests that most or even all positive cG×E findings represent type I errors.In this new era of big data and small effects, a recalibration of views about groundbreaking findings is necessary. Well-powered direct replications deserve more attention than novel cG×E findings and indirect replications.

The development of social behavior could be affected by stressful parenting. The mineralocorticoid receptor, one of the two main receptors for the stress hormone cortisol, plays a vital role in adequate responses to stress. Therefore, the effects of stressful parenting on social development (i.e., empathic concern, perspective taking and prosocial behavior) may be moderated by functional genetic variation in mineralocorticoid receptor haplotypes (a combination of alleles). A group of 343 adolescents (44.3% females) was followed from the age of 13 until 24 years. Growth curve analyses showed lower levels of prosocial behaviors and a slower increase in empathic concern and perspective taking in adolescents who reported more stressful parenting. In contrast, relatively higher levels of prosocial behavior, empathic concern and perspective taking were present in combination with stress resilient mineralocorticoid receptor haplotypes. Despite sex differences in social development with earlier social development for girls, no consistent sex differences were found with regard to mineralocorticoid receptor haplotypes. The current study showed that genetic variation in mineralocorticoid receptor impacts the social development during adolescence and young adulthood.

Stress responses are controlled by the hypothalamus pituitary adrenal (HPA)-axis and maladaptive stress responses are associated with the onset and maintenance of stress-related disorders such as major depressive disorder (MDD). Genes that play a role in the HPA-axis regulation may likely contribute to the relation between relevant neurobiological substrates and stress-related disorders. Therefore, we performed gene-wide analyses for 30 a priori literature-based genes involved in HPA-axis regulation in 2014 subjects (34% male; mean age: 42.5) to study the relations with lifetime MDD diagnosis, cortisol awakening response, and dexamethasone suppression test (DST) levels (subsample N=1472) and hippocampal and amygdala volume (3T MR images; subsample N=225). Additionally, gene by childhood maltreatment (CM) interactions were investigated. Gene-wide significant results were found for dexamethasone suppression (CYP11A1, CYP17A1, POU1F1, AKR1D1), hippocampal volume (CYP17A1, CYP11A1, HSD3B2, PROP1, AVPRA1, SRD5A1), amygdala volume (POMC, CRH, HSD3B2), and lifetime MDD diagnosis (FKBP5 and CRH), all permutation p-values<0.05. Interactions with CM were found for several genes; the strongest interactions were found for NR3C2, where the minor allele of SNP rs17581262 was related to smaller hippocampal volume, smaller amygdala volume, higher DST levels, and higher odds of MDD diagnosis only in participants with CM. As hypothesized, several HPA-axis genes are associated with stress-related endophenotypes including cortisol response and reduced brain volumes. Furthermore, we found a pleiotropic interaction between CM and the mineralocorticoid receptor gene, suggesting that this gene plays an important moderating role in stress and stress-related disorders.

Prosocial behavior is an important aspect of normal social and psychological development. Adult and child twin studies typically estimate the heritability of prosocial behavior to be between 30 and 50%, although relatively little is known about genetic and environmental influences upon prosocial behavior in adolescence. We therefore examined reports of prosocial behavior in a large longitudinal family study of 1160 adolescent twin pairs (aged between 13 and 19 years). Prosocial behavior was assessed at two time points by self-report and at the second time point by additional parent-ratings using the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). Adolescent females were reported to be significantly more prosocial than males (p <.001). Univariate analyses primarily showed moderate heritability and large nonshared environmental influences. There was a moderate genetic correlation between self- and parent-reported prosocial behaviour, suggesting that both types of rater were tapping into genetically overlapping constructs. Longitudinal analyses revealed that continuity was largely explained by genes. Unique environmental influences were predominantly time-specific and were the major source of individual differences.

Stress is a part of every life to varying degrees, but individuals differ in their stress vulnerability. Stress is usefully viewed from a biological perspective; accordingly, it involves activation of neurobiological systems that preserve viability through change or allostasis. Although they are necessary for survival, frequent neurobiological stress responses increase the risk of physical and mental health problems, perhaps particularly when experienced during periods of rapid brain development. Recently, advances in noninvasive measurement techniques have resulted in a burgeoning of human developmental stress research. Here we review the anatomy and physiology of stress responding, discuss the relevant animal literature, and briefly outline what is currently known about the psychobiology of stress in human development, the critical role of social regulation of stress neurobiology, and the importance of individual differences as a lens through which to approach questions about stress experiences during development and child outcomes.

Researchers often hypothesize moderated effects, in which the effect of an independent variable on an outcome variable depends on the value of a moderator variable. Such an effect reveals itself statistically as an interaction between the independent and moderator variables in a model of the outcome variable. When an interaction is found, it is important to probe the interaction, for theories and hypotheses often predict not just interaction but a specific pattern of effects of the focal independent variable as a function of the moderator. This article describes the familiar pick-a-point approach and the much less familiar Johnson-Neyman technique for probing interactions in linear models and introduces macros for SPSS and SAS to simplify the computations and facilitate the probing of interactions in ordinary least squares and logistic regression. A script version of the SPSS macro is also available for users who prefer a point-and-click user interface rather than command syntax.

Childhood trauma is a potent risk factor for developing depression in adulthood, particularly in response to additional stress. We here summarize results from a series of clinical studies suggesting that childhood trauma in humans is associated with sensitization of the neuroendocrine stress response, glucocorticoid resistance, increased central corticotropin-releasing factor (CRF) activity, immune activation, and reduced hippocampal volume, closely paralleling several of the neuroendocrine features of depression. Neuroendocrine changes secondary to early-life stress likely reflect risk to develop depression in response to stress, potentially due to failure of a connected neural circuitry implicated in emotional, neuroendocrine and autonomic control to compensate in response to challenge. However, not all of depression is related to childhood trauma and our results suggest the existence of biologically distinguishable subtypes of depression as a function of childhood trauma that are also responsive to differential treatment. Other risk factors, such as female gender and genetic dispositions, interfere with components of the stress response and further increase vulnerability for depression. Similar associations apply to a spectrum of other psychiatric and medical disorders that frequently coincide with depression and are aggravated by stress. Taken together, this line of evidence demonstrates that psychoneuroendocrine research may ultimately promote optimized clinical care and help prevent the adverse outcomes of childhood trauma.

基于生态系统理论和动机?意志整合模型, 采用问卷法以930名青少年(年龄 = 15.24 ± 1.66岁)及其父母为研究对象, 构建一个有调节的中介模型, 从家长与孩子双视角分析孩子体验到的亲子关系和父母教育卷入对青少年抑郁、自伤和自杀意念的影响路径。结果显示：(1)相比低亲子关系?低教育卷入一致的个体, 高亲子关系?高教育卷入的青少年有着更低水平的挫败感, 且相比于低亲子关系?高教育卷入的青少年, 有着高亲子关系?低教育卷入的个体表现出更低水平的挫败感; (2)挫败感在亲子关系?教育卷入与青少年抑郁、自伤和自杀意念之间起部分中介作用; (3)人生意义感调节该中介模型后半段, 即挫败感对青少年抑郁、自伤和自杀意念的影响, 具体表现为随着人生意义感的增加, 挫败感对抑郁、自伤和自杀意念的影响逐渐减小。研究从家庭关系中家长与孩子双视角, 揭示了挫败感和人生意义感的中介与调节作用, 为青少年抑郁、自伤和自杀意念的发生机制提供更多解释路径。

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

Childhood maltreatment has been shown to have a stronger etiological relation to depression onset in adolescence than in adulthood. We propose that a maltreatment history may more strongly sensitize individuals to the depressogenic effects of proximal stressful life events in adolescence compared to adulthood. In an amalgamated sample of 176 unipolar depressed adolescents (age 12-17) and emerging adults (age 18-29), we examined the moderating role of age group on the relation of childhood maltreatment to sensitization to stressors that occurred just prior to episode onset. Among adolescents, but not among adults, those with a maltreatment history reported a lower severity level of life events prior to episode onset than reported by those without such a history. Further, this relation was specific to emotional abuse, and not physical or sexual abuse. We suggest that the pathological mechanisms associated with translating childhood maltreatment to depression may differ across developmental periods. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Although the quality of the attachment relationship is often cited as an important determinant of development, the extent of impact of this environmental influence in shaping behavioral outcomes has been a matter of considerable debate. This may, in part, be because of the variability in methodologies used for assessing attachment across infancy, childhood, and adolescence, including behavioral, representational, and questionnaire measures of attachment. Previous meta-analyses of the relations between attachment and internalizing and externalizing problems have focused on the behavioral measures of attachment used primarily in infancy. The current meta-analysis is a comprehensive examination of the literature on attachment and behavioral problems in children aged 3-18 years, focusing on the representational and questionnaire measures most commonly used in this age range. When secure attachment was compared with insecure attachment, modest associations with internalizing behavior (165 studies; 48,224 families; d =.58; 95% confidence interval [CI] [.52-.64]) were found. Multivariate moderator analyses were used to disentangle the unique influence of each significant univariate moderator more precisely, and results revealed that effect sizes decreased as the child aged, and were larger in studies in which the participants were ethnically White, where the child was the problem informant, and when the internalizing measure was depressive symptoms. Attachment and externalizing behavior were also associated (116 studies; 24,689 families; d =.49; 95% CI [42-.56]), and effect sizes were larger in ethnically White samples, and in those where the child was the problem informant. Avoidant, ambivalent, and disorganized attachment classifications were associated with internalizing behavior, but only disorganized attachment was associated with externalizing behavior.(c) 2016 APA, all rights reserved).

This review discusses neurobiological studies of oppositional defiant disorder and conduct disorder within the conceptual framework of three interrelated mental domains: punishment processing, reward processing, and cognitive control. First, impaired fear conditioning, reduced cortisol reactivity to stress, amygdala hyporeactivity to negative stimuli, and altered serotonin and noradrenaline neurotransmission suggest low punishment sensitivity, which may compromise the ability of children and adolescents to make associations between inappropriate behaviors and forthcoming punishments. Second, sympathetic nervous system hyporeactivity to incentives, low basal heart rate associated with sensation seeking, orbitofrontal cortex hyporeactiviy to reward, and altered dopamine functioning suggest a hyposensitivity to reward. The associated unpleasant emotional state may make children and adolescents prone to sensation-seeking behavior such as rule breaking, delinquency, and substance abuse. Third, impairments in executive functions, especially when motivational factors are involved, as well as structural deficits and impaired functioning of the paralimbic system encompassing the orbitofrontal and cingulate cortex, suggest impaired cognitive control over emotional behavior. In the discussion we argue that more insight into the neurobiology of oppositional defiance disorder and conduct disorder may be obtained by studying these disorders separately and by paying attention to the heterogeneity of symptoms within each disorder.

Childhood adversity (CA) is associated with adult mental disorders, but the mechanisms underlying this association remain inadequately understood. Stress sensitization, whereby CA increases vulnerability to mental disorders following adult stressful life events, has been proposed as a potential mechanism. We provide a test of the stress sensitization hypothesis in a national sample.We investigated whether the association between past-year stressful life events and the 12-month prevalence of major depression, post-traumatic stress disorder (PTSD), other anxiety disorders, and perceived stress varies according to exposure to CA. We used data from the National Epidemiological Survey of Alcohol and Related Conditions (NESARC) (n=34 653).Past-year stressful life events were associated with an increased risk of major depression, PTSD, anxiety disorders, and perceived stress. However, the magnitude of the increased risk varied according to respondents' history of CA. For example, past-year major stressors were associated with a 27.3% increase in the 12-month risk of depression among individuals with 3 CAs and a 14.8% increased risk among individuals without CAs. Stress sensitization effects were present for depression, PTSD, and other anxiety disorders in women and men, although gender differences were found in the threshold of past-year stress needed to trigger such effects. Stress sensitization was most evident among individuals with 3 CAs.CA is associated with increased vulnerability to the deleterious mental health effects of adult stressors in both men and women. High levels of CA may represent a general diathesis for multiple types of psychopathology that persists throughout the life course.

Depression has been linked to increased cortisol reactivity and differences in limbic brain volumes, yet the mechanisms underlying these alterations are unclear. One main hypothesis is that stress causes these effects. This is supported by animal studies showing that chronic stress or glucocorticoid administration can lead to alterations in hippocampal and amygdala structures. Relatedly, life stress is cited as one of the major risk factors for depression and candidate gene studies have related variation in stress-system genes to increased prevalence and severity of depression. The present study tested the hypothesis that genetic profile scores combining variance across 10 single nucleotide polymorphisms from four stress-system genes (CRHR1, NR3C2, NR3C1, and FKBP5) and early life stress would predict increases in cortisol levels during laboratory stressors in 120 preschool-age children (3-5 years old), as well as hippocampal and amygdala volumes assessed with MRI in these same children at school age (7-12 years old). We found that stress-system genetic profile scores positively predicted cortisol levels while the number of stressful/traumatic life events experienced by 3-5 years old negatively predicted cortisol levels. The interaction of genetic profile scores and early life stress predicted left hippocampal and left amygdala volumes. Cortisol partially mediated the effects of genetic variation and life stress on limbic brain volumes, particularly on left amygdala volume. These results suggest that stress-related genetic and early environmental factors contribute to variation in stress cortisol reactivity and limbic brain volumes in children, phenotypes associated with depression in adulthood.

The current study is the first to examine the relation of childhood abuse and neglect history to theory of mind decoding accuracy as moderated by depression. Fifty-five young adults with current or lifetime unipolar depression diagnosis and 70 never-depressed young adults completed the 'Reading the Mind in the Eyes task,' (RMET). Childhood emotional abuse, physical abuse, and neglect were assessed with a gold-standard contextual interview with standardized, independent ratings. Poorer RMET accuracy was associated with a history of emotional abuse in the depressed group and a history of physical abuse in the non-depressed group. In contrast, across both groups, those with a history of neglect showed significantly enhanced theory of mind decoding accuracy compared to those without. Further, differential accuracy across positive, negative, and neutral valenced stimuli in the RMET was observed in each model. These findings indicate that distinct theory of mind performance results from early experiences of threat versus deprivation, and suggest that early intervention may be most successful in preventing negative interpersonal outcomes of maltreatment by focusing on remediating theory of mind deficits resulting from abuse, and tempering heightened sensitivity in those exposed to neglect.Copyright © 2018 Elsevier B.V. All rights reserved.

This report describes the state of the art in distinguishing data generated by differential susceptibility from diathesis-stress models. We discuss several limitations of existing practices for probing interaction effects and offer solutions that are designed to better differentiate differential susceptibility from diathesis-stress models and quantify their corresponding implications. In addition, we demonstrate the utility of these methods by revisiting published evidence suggesting that temperamental difficulty serves as a marker of enhanced susceptibility to early maternal caregiving across a range of outcome domains in the NICHD Study of Early Child Care and Youth Development. We find that, with the exception of mother reports of psychopathology, there is consistent evidence in the Study of Early Child Care and Youth Development that the predictive significance of early sensitivity is moderated by difficult temperament over time. However, differential susceptibility effects emerged primarily for teacher reports of academic skills, social competence, and symptomatology. In contrast, effects more consistent with the diathesis-stress model were obtained for mother reports of social skills and objective tests of academic skills. We conclude by discussing the value of the application of this work to the next wave of Gene × Environment studies focused on early caregiving experiences.

A number of studies have demonstrated that stress is involved in all aspects of smoking behavior, including initiation, maintenance and relapse. The mineralocorticoid (MR) and glucocorticoid (GR) receptors are expressed in several brain areas and play a key role in negative feedback of the hypothalamic-pituitary-adrenal (HPA) axis. As nicotine increases the activation of the HPA axis, we wondered if functional SNPs (single nucleotide polymorphisms) in MR and GR coding genes (NR3C2 rs5522 and NR3C1 rs6198, respectively) may be involved in smoking susceptibility. The sample included 627 volunteers, of which 514 were never-smokers and 113 lifetime smokers. We report an interaction effect between rs5522 and rs6198 SNPs. The odds ratio (OR) for the presence of the NR3C2 rs5522 Val allele in NR3C1 rs6198 G carriers was 0.18 (P = 0.007), while in rs6198 G noncarriers the OR was 1.83 (P = 0.027). We also found main effects of the NR3C1 rs6198 G allele on number of cigarettes smoked per day (P = 0.027) and in total score of the Fagerström Test for Nicotine Dependence (P = 0.007). These findings are consistent with a possible link between NR3C2 and NR3C1 polymorphisms and smoking behavior and provide a first partial replication for a nominally significant GWAS finding between NR3C2 and tobacco smoking.

Several studies provide evidence for a relationship between childhood abuse and suicidality across the lifespan. To examine this association in the context of the Interpersonal Psychological Theory of Suicide (IPTS), we investigated whether its constructs thwarted belongingness, perceived burdensomeness and capability for suicide are potential mediators.Eighty-four German psychiatric inpatients with unipolar depression (M = 37.6 years, 69% female) and current or lifetime suicidal ideation were included. For the assessment we used the Childhood Trauma Screener (CTS), the Rasch-based Screening for Depression (DESC-I), the Interpersonal Needs Questionnaire (INQ), the German Capability for Suicide Questionnaire (GCSQ), the Beck Scale for Suicide Ideation (BSS) and the Suicide Behaviors Questionnaire-Revised (SBQ-R). Simple and multiple mediator analyses were applied.Most patients (70%) had experienced childhood abuse. Emotional abuse showed an indirect association with suicidal ideation via thwarted belongingness and perceived burdensomeness, whereas physical and sexual abuse were indirectly related to suicide risk via capability for suicide.The small sample size and the cross-sectional design are limiting factors of the present study.Childhood abuse is a common experience of inpatients with unipolar depression. This study showed its indirect effects on suicidal ideation and risk for suicide, mediated by the constructs of the IPTS. Further research should investigate this issue in other populations and clinicians should be aware of the devastating effects of childhood abuse.Copyright © 2018. Published by Elsevier B.V.

Research suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene-environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis-related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14-17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene-environment interactions individually accounted for 5%-8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene-environmental interactions linked to affective outcomes among adolescents.

DNA methylation is a chemical modification of DNA that confers, upon identical sequences, different identities that are reflected in different gene expression programming. DNA methylation has a well-established role in cellular differentiation by providing a mechanism for one genome to express multiple phenotypes in a multicellular organism. Recent data point however to the possibility that in addition to the innate process of cellular differentiation, DNA methylation can serve as a genome adaptation mechanism, adapting genome function to changing environmental contexts including social environments. A critical time point for this process is early life when cues from the social and physical environments define lifelong trajectories of physical and mental health. DNA methylation and additional epigenetic modifications could therefore serve as molecular links between 'nurture' and 'nature'. Data that are consistent with this new role for DNA methylation as a mechanism for conferring an 'environment' specific identity to DNA will be discussed.© 2012 John Wiley & Sons A/S.

The main aim of the current study was to investigate whether 2 gene expression in the postmortem brain of rs7208505 genotype are altered in suicide victims from a Mexican population.In this study, we report a genetic analysis of expression levels of the 2 gene in the prefrontal cortex of the postmortem brain of suicidal subjects ( = 22) compared to subjects who died of causes other than suicide ( = 22) in a Mexican population using RT-qPCR assays. Additionally, we genotyped the rs7208505 polymorphism in suicide victims ( = 98) and controls ( = 88) and we evaluate the association of genotypes for the SNP rs7208505 with expression level of 2.The results showed that the expression of the 2 gene was significantly higher in suicide victims compared to control subjects ( = 0.044). Interestingly, we observed a greater proportion of allele A of the rs7208505 in suicide victims than controls. Even though there was no association between the SNP with suicide in the study population we found a significative association of the expression level from 2 with the allele A of the rs7208505 and suicide.The evidence suggests that the expression of 2 in the prefrontal cortex may be a critical factor in the etiology of suicidal behavior.

The MR is an important regulator of the hypothalamic-pituitary-adrenal (HPA) axis and a prime target for corticosteroids. There is increasing evidence from both clinical and preclinical studies that the MR has different effects on behavior and mood in males and females. To investigate the hypothesis that the MR sex-dependently influences the relation between childhood maltreatment and depression, we investigated three common and functional MR haplotypes (GA, CA, and CG haplotype, based on rs5522 and rs2070951) in a population-based cohort (N = 665) and an independent clinical cohort from the Netherlands Study of Depression and Anxiety (NESDA) (N = 1639). The CA haplotype sex-dependently moderated the relation between childhood maltreatment and depressive symptoms both in the population-based sample (sex × maltreatment × haplotype: β = -4.07, P = 0.029) and in the clinical sample (sex × maltreatment × haplotype, β = -2.40, P = 0.011). Specifically, female individuals in the population-based sample were protected (β = -4.58, P = 2.0 e(-5)), whereas males in the clinical sample were at increased risk (β = 2.54, P = 0.0022). In line with these results, female GA haplotype carriers displayed increased vulnerability in the population-based sample (β = 4.58, P = 7.5 e(-5)) whereas male CG-carriers showed increased resilience in the clinical sample (β = -2.71, P = 0.016). Consistently, we found a decreased lifetime MDD risk for male GA haplotype carriers following childhood maltreatment but an increased risk for male CA haplotype carriers in the clinical sample. In both samples, sex-dependent effects were observed for GA-GA diplotype carriers. In summary, sex plays an important role in determining whether functional genetic variation in MR is beneficial or detrimental, with an apparent female advantage for the CA haplotype but male advantage for the GA and CG haplotype. These sex-dependent effects of MR on depression susceptibility following childhood maltreatment are relevant in light of the increased prevalence of mood disorders in women and point to a sex-specific role of MR in the etiology of depression following childhood maltreatment.Copyright © 2015 Elsevier Ltd. All rights reserved.

Behavioral genetic research supports polygenic models of depression in which many genetic variations each contribute a small amount of risk, and prevailing diathesis-stress models suggest gene-environment interactions (G×E). Multilocus profile scores of additive risk offer an approach that is consistent with polygenic models of depression risk. In a first demonstration of this approach in a G×E predicting depression, we created an additive multilocus profile score from 5 serotonin system polymorphisms (1 each in the genes HTR1A, HTR2A, HTR2C, and 2 in TPH2). Analyses focused on 2 forms of interpersonal stress as environmental risk factors. Using 5 years of longitudinal diagnostic and life stress interviews from 387 emerging young adults in the Youth Emotion Project, survival analyses show that this multilocus profile score interacts with major interpersonal stressful life events to predict major depressive episode onsets (hazard ratio [HR] = 1.815, p =.007). Simultaneously, there was a significant protective effect of the profile score without a recent event (HR = 0.83, p =.030). The G×E effect with interpersonal chronic stress was not significant (HR = 1.15, p =.165). Finally, effect sizes for genetic factors examined ignoring stress suggested such an approach could lead to overlooking or misinterpreting genetic effects. Both the G×E effect and the protective simple main effect were replicated in a sample of early adolescent girls (N = 105). We discuss potential benefits of the multilocus genetic profile score approach and caveats for future research.(c) 2015 APA, all rights reserved).

There are three representative theory models about gene-environment interaction: diathesis-stress model, differential susceptibility model and vantage sensitivity model. Diathesis-stress model advocates that one who stays near ink gets stained black, vantage sensitivity model, however, suggests that one who stays near vermilion gets stained red, and differential susceptibility model is eclectic. To verify the above-mentioned model has been one of the focuses of research on gene-environment interaction. The grouping regression analysis and hierarchical regression analysis are the traditional methods to test these three models, and the region of significance and the re-parameterized regression model are the newly emerging ones. Future research could focus on the issues of domain-specificity, the ethnic difference, developmental change and the underlying mechanism of the gene-environment interaction. The measurement and method to examine the interaction between gene and environment also remain improved.

素质?压力模型、不同易感性模型和优势敏感性模型是当前有关基因?环境交互作用的三种代表性理论模型。素质?压力模型认为&ldquo;近墨者黑&rdquo;或&ldquo;出淤泥而不染&rdquo;, 优势反应敏感性模型认为&ldquo;近朱者赤&rdquo;, 而不同易感性模型则兼收并蓄, 认为某些个体近墨则黑, 近朱则赤。检验上述模型的现实有效性是当前基因?环境交互作用研究领域的热点问题之一。概观而言, 分组回归和分层回归是常用的传统检验方法, 显著性区域分析法和新参数回归模型法则是新近兴起的。未来研究需要进一步探索三种模型的领域特殊性、种族差异等问题, 检验这些模型的方法也有待改善。

采用环境×基因×环境(E×G×E)研究设计, 以637名青少年为被试, 考察了负性生活事件、COMT基因Val158Met多态性和父母教养行为对青少年早期抑郁的影响。结果发现：负性生活事件对青少年早期抑郁具有显著正向预测作用, 且COMT基因Val158Met多态性和父亲积极教养行为在其中起调节作用, 但该调节作用仅存在于男青少年群体中：在携带Val/Val基因型的男青少年中, 当父亲积极教养行为水平较低时, 青少年的抑郁水平随负性生活事件的增多而显著上升, 当父亲积极教养行为水平较高时, 负性生活事件对抑郁无显著预测作用; 在携带Met等位基因的男青少年中, 上述交互作用不显著。

We systematically examined the factor structure and criterion validity across the full scale and 10 short forms of the Center for Epidemiological Studies Depression Scale (CES-D) with Chinese youth. Participants were 5,434 Chinese adolescents in Grades 7 to 12 who completed the full CES-D; 612 of them further completed a structured diagnostic interview with the major depressive disorder (MDD) module of the Kiddie Schedule for Affective Disorder and Schizophrenia for School-age Children. Using a split-sample approach, a series of 4-, 3-, 2-, and 1-factor models were tested using exploratory structural equation modeling and cross-validated using confirmatory factor analysis; the dimensionality was also evaluated by parallel analysis in conjunction with the scree test and aided by factor mixture analysis. The results indicated that a single-factor model of depression with a wording method factor fitted the data well, and was the optimal structure underlying the scores of the full and shortened CES-D. Additionally, receiver operating characteristic curve analyses for MDD case detection showed that the CES-D full-scale scores accurately detected MDD youth (area under the curve [AUC] =.84). Furthermore, the short-form scores produced comparable AUCs with the full scale (.82 to.85), as well as similar levels of sensitivity and specificity when using optimal cutoffs. These findings suggest that depression among Chinese adolescents can be adequately measured and screened for by a single-factor structure underlying the CES-D scores, and that the short forms provide a viable alternative to the full instrument. (PsycINFO Database Record(c) 2018 APA, all rights reserved).

The binding protein FKBP5 is an important modulator of the function of the glucocorticoid receptor, the main receptor of the stress hormone system. This turns the FKBP5 gene into a key candidate for gene-environment interactions, which are considered critical for pathogenesis of stress-related disorders. The authors explored gene-environment interactions between FKBP5 gene variants and adverse life events in predicting the first occurrence of a major depressive episode.The analyses were based on 884 Caucasians in a 10-year prospective community study. At baseline, they were 14-24 years old and did not fulfill criteria for a major depressive episode. The DSM-IV-based Munich Composite International Diagnostic Interview was used to assess adverse life events preceding baseline and major depressive episodes during follow-up. On the basis of previous findings, five single-nucleotide polymorphisms (SNPs) within the FKBP5 gene were selected for genotyping.While the authors did not observe genetic main effects, they found interactions between the five SNPs and traumatic (but not separation) events, with the strongest effect for severe trauma. The effect of trauma on incident major depressive episodes was evident among subjects homozygous for the minor alleles but not subjects with other genotypes. The findings were replicated in the U.K. Environmental Risk Longitudinal Twin Study.These hypothesis-driven results suggest that an interaction between FKBP5 genotype and trauma is involved in the onset of depression. Subjects homozygous for the minor alleles of the investigated FKBP5 SNPs seem to be particularly sensitive to effects of trauma exposure in terms of triggering depression onset.