Early-life adversity and risk for depression and anxiety: The role of interpersonal support.

Early-life adversity is a major risk factor for psychopathology, but not all who experience adversity develop psychopathology. The current study evaluated whether the links between child and adolescent adversity and depression and anxiety were described by general benefits and/or buffering effects of interpersonal support. Data from 456 adolescents oversampled on neuroticism over a 5-year period were examined in a series of discrete-time survival analyses to predict subsequent disorder onsets. Models examined linear, quadratic, and interactive effects of interpersonal support over time, as measured by chronic interpersonal stress interview ratings. Results did not support buffering effects of interpersonal support against either child or adolescent adversity in predicting depression or anxiety. However, there was support for the general benefits model of interpersonal support as evidenced by follow-up analyses of significant quadratic effects of interpersonal support, demonstrating that higher interpersonal support led to decreased likelihood of depression and anxiety onsets. Secondary analyses demonstrated that effects of interpersonal support remained after accounting for baseline depression and anxiety diagnoses. Further, quadratic effects were driven by social domains as opposed to familial domains when considering child adversity. Implications for interventions and randomized controlled prevention trials regarding interpersonal relationships are discussed.

Prenatal Maternal Stress and Pediatric Asthma Across Development: Adolescent Female-Specific Vulnerability.

Prenatal maternal stress (PNMS) is linked to physical sequelae in offspring, including childhood asthma. This study sought to examine the roles of objective and subjective PNMS in the development of asthma at offspring ages 5 and 15. The sample included 815 mother-child dyads from the Mater Misericordiae Mothers' Hospital-University of Queensland Study of Pregnancy. PNMS was measured via retrospective self-report during pregnancy and 3-5 days after birth. Postnatal maternal stress was measured at offspring age 5. Objective PNMS was associated with elevated asthma risk at age 5 (OR 1.21, 95% CI 1.00, 1.45, p = 0.05), albeit not above concurrent postnatal stress. Sex moderated the association between PNMS and asthma at age 15, controlling for postnatal stress. Sex stratified analyses revealed a positive association between objective PNMS and age 15 asthma in females, but not males. Results provide evidence that PNMS may impact asthma outcomes in adolescence.

HPA-axis multilocus genetic profile score moderates the association between maternal prenatal perceived stress and offspring depression in early adulthood.

Maternal stress during pregnancy can cause alterations to the fetal hypothalamus-pituitary-adrenal (HPA) axis, a phenomenon known as fetal programming that may have lasting effects on offspring outcomes, including depression. Evidence suggests that these effects may vary with respect to the offspring's genetic risk. Nonetheless, few studies have examined these effects into adulthood, when risk for depression onset is highest. The present study builds upon the extant literature by examining the interaction of maternal prenatal perceived stress (MPPS) and offspring HPA-axis polygenic risk to predict offspring depression in early adulthood. A total of 381 mother-child dyads participated in a prospective, longitudinal study that spanned from pregnancy until offspring were 20 years of age. Polygenic risk was defined by a multilocus genetic profile score (MGPS) that reflected the additive risk of three HPA-axis candidate genes. The results indicated that the interaction of MPPS and HPA-axis MGPS confers risk for offspring depression at age 20, in line with the differential susceptibility model. This interaction may be specific to prenatal stress, as maternal stress during early childhood did not interact with genetic risk to predict depression. These findings provide the first evidence that genetic variants that are associated with the HPA axis may act in a polygenic, additive fashion to moderate the association between fetal programming and adult depression.

Chronic Stress in Vocational and Intimate Partner Domains as Predictors of Depressive Symptoms After Breast Cancer Diagnosis.

BACKGROUND: After cancer diagnosis, depressive symptoms are elevated on average and decline over time, but substantial variability is apparent. Few studies have examined to what extent chronic stress in distinct life domains affects depressive symptoms. PURPOSE: Chronic stress in vocational and intimate partner life domains, and their interaction, were tested as predictors of depressive symptoms after breast cancer diagnosis. METHODS: Women (N = 460) completed validated interviews regarding chronic stress in specific life domains shortly after diagnosis and a measure of depressive symptoms every 6 weeks for 6 months. RESULTS: In latent growth curve modeling analyses, greater chronic stress in work (b = 2.90; p < .001) and intimate partner domains (b = 1.38, p = .02) was associated with higher depressive symptoms at study entry (intercept), and greater work stress predicted faster recovery from depressive symptoms over time (b = -0.10; p = .01). The two domains of chronic stress also interacted significantly on depressive symptoms at study entry (b = -1.54; p < .02) and over time (b = 0.14; p < .001). Greater work stress was associated with higher depressive symptoms at study entry regardless of intimate partner stress, but greater intimate partner stress was associated with higher depressive symptoms when work stress was low. The decline over 6 months in initially elevated depressive symptoms predicted by high work stress was significantly steeper when intimate partner stress was low. CONCLUSIONS: Targeting interventions to recently diagnosed breast cancer patients living with chronically stressful vocational and intimate partner life circumstances could be worthwhile.

Transdiagnostic pathways from early social stress to psychopathology: a 20-year prospective study.

BACKGROUND: Adverse family environments confer susceptibility to virtually all psychiatric problems. This study evaluated two possible models to explain this diversity of associations. Stressful family circumstances during childhood could either activate general, transdiagnostic liabilities to mental disorder or promote numerous disorder-specific liabilities. METHODS: We recruited a high-risk sample of 815 mother-offspring pairs and assessed social stressors in the family context prospectively from the perinatal period through offspring age 5. We factor analyzed offspring mental disorder diagnoses at age 20 to parse transdiagnostic and disorder-specific dimensions of psychopathology. RESULTS: Structural analyses revealed nearly equivalent prospective effects of early family stress on overarching Internalizing (ß = .30) and Externalizing (ß = .29) dimensions. In contrast, there was no evidence of disorder-specific effects. CONCLUSIONS: Social stressors early in life activate transdiagnostic, and not disorder-specific, liabilities to psychopathology. A focus on higher-order dimensions of psychopathology could accelerate etiological research and intervention efforts for stress-linked mental disorders.

Risk Factors for Depression: An Autobiographical Review.

I have been given a priceless opportunity to reflect on my career in the remarkably productive field of risk factors for depression. Psychological research on depression exploded in the early years of my work. I try to give an account of the choices and challenges, and reflect on the influences, some calculated and some serendipitous, that determined the paths I have followed. I focus mostly on the robust depression risk factors that have influenced my research, including dysfunctional cognitions, stressful life events and circumstances, parental depression, interpersonal dysfunction, and being female, and I cover some of what I did but also the influential work of others. This is a selective review of depression research in the past 40 or so years, noting some of the big developments that set the stage for the remarkable activity that continues today. In the conclusion, there is a brief statement of aspirations for future developments in our field.

Independent and relative effects of stress, depressive symptoms, and affect on college students' daily health behaviors.

Stress and depressive symptoms are associated with maladaptive health behavior practices such as unhealthy eating, sedentary behavior, insufficient sleep, and substance use. The relative and interactive effects of stress and depressive symptoms on health behavior practices are less well understood. The present study examined these processes in a daily diary study of 127 college students. Results from hierarchical generalized linear models indicated that depressive symptoms, and chronic and daily stress, but not acute stressful life events, were significantly associated with a composite score of daily maladaptive health behavior engagement (depressive symptoms b = .01, SE= .00, p < .01; chronic stress, b = .03, SE= .01, p < .01; daily stress, b = .01, SE= .01, p = .02); unexpectedly, the effect of stress on health behaviors was not moderated by depressive symptoms. Additionally, results demonstrated that the effect of depressive symptoms on health behaviors was mediated by fluctuations in daily negative affect. These results bear implications for intervention during a crucial period in the development of mental and physical health.

Parental Serotonin Transporter Polymorphism (5-HTTLPR) Moderates Associations of Stress and Child Behavior With Parenting Behavior.

The serotonin transporter-linked polymorphic region (5-HTTLPR) is associated with caregiving in nonhuman animals and with affective and cognitive correlates of human parenting, yet its association with human parenting is largely unknown. Using a well-characterized sample of parents and offspring, we evaluated the association of parental 5-HTTLPR with observed positive and negative parenting behavior, as well as its biologically plausible moderation of child-related stress and disruptive child behavior as predictors of parenting. One hundred and sixty-two parents (86% mothers) and their 6- to 9-year-old children with and without attention-deficit/hyperactivity disorder were ascertained using multiple methods including structured interviews, rating scales, and observed parent-child interaction, yielding strong measures of key constructs. Controlling for multiple youth-level (e.g., sex, 5-HTTLPR genotype, disruptive behavior) and parent-level (e.g., demographics, depression, attention-deficit/hyperactivity disorder) factors, parents with an S allele exhibited significantly less observed positive parenting than those with the LL genotype. Significant Gene × Environment interactions were also observed: Child-related stress was negatively associated with observed parental negativity among SS/SL genotype parents but not LL genotype parents; next, observed disruptive child behavior was positively associated with parental negativity for both genotypes, but the effect was strongest in SS/SL parents. These preliminary findings suggest that parental 5-HTTLPR is uniquely associated with positive and negative parenting behavior, with more specific patterns according to child-related stress and disruptive child behavior. We consider implications for future research evaluating genetic influences on parenting as well as considerations for designing and delivering parenting-based interventions.

Association of Maternal Depressive Symptoms and Offspring Physical Health in Low-Income Families.

Objectives The present study sought to examine the association between maternal depressive symptoms and characteristics of offspring physical health, including health status, health behaviors, and healthcare utilization, among low-income families. Maternal engagement was explored as a mediator of observed effects. Methods Cross-sectional survey data from a community sample of 4589 low-income women and their preschool-age children participating in the WIC program in Los Angeles County were analyzed using logistic, Poisson, and zero-inflated negative binomial regression. Mediation was tested via conditional process analyses. Results After controlling for the effects of demographic characteristics including maternal health insurance coverage, employment status, education, and preferred language, children of depressed women (N = 1025) were significantly more likely than children of non-depressed women (N = 3564) to receive a "poor" or "fair" maternal rating of general health (OR 2.34), eat fewer vegetables (IRR: 0.94) more sweets (IRR: 1.20) and sugary drinks daily (IRR: 1.32), and consume fast food more often (OR 1.21). These children were also less likely to have health insurance (OR 1.59) and more likely to receive medical care from a public medical clinic or hospital emergency room (OR 1.30). Reduced maternal engagement partially mediated associations between maternal depressive symptoms and several child health outcomes including poor diet, health insurance coverage, and use of public medical services. Conclusions for Practice Maternal depressive symptoms are associated with poor health among preschool-age children in low-income families. Prevention, screening, and treatment efforts aimed at reducing the prevalence of maternal depression may positively affect young children's health.

Chronic and episodic stress predict physical symptom bother following breast cancer diagnosis.

Breast cancer patients often experience adverse physical side effects of medical treatments. According to the biobehavioral model of cancer stress and disease, life stress during diagnosis and treatment may negatively influence the trajectory of women's physical health-related adjustment to breast cancer. This longitudinal study examined chronic and episodic stress as predictors of bothersome physical symptoms during the year after breast cancer diagnosis. Women diagnosed with breast cancer in the previous 4 months (N = 460) completed a life stress interview for contextual assessment of chronic and episodic stress severity at study entry and 9 months later. Physical symptom bother (e.g., pain, fatigue) was measured at study entry, every 6 weeks through 6 months, and at nine and 12 months. In multilevel structural equation modeling (MSEM) analyses, both chronic stress and episodic stress occurring shortly after diagnosis predicted greater physical symptom bother over the study period. Episodic stress reported to have occurred prior to diagnosis did not predict symptom bother in MSEM analyses, and the interaction between chronic and episodic stress on symptom bother was not significant. Results suggest that ongoing chronic stress and episodic stress occurring shortly after breast cancer diagnosis are important predictors of bothersome symptoms during and after cancer treatment. Screening for chronic stress and recent stressful life events in the months following diagnosis may help to identify breast cancer patients at risk for persistent and bothersome physical symptoms. Interventions to prevent or ameliorate treatment-related physical symptoms may confer added benefit by addressing ongoing non-cancer-related stress in women's lives.

The Effects of Childhood and Adolescent Adversity on Substance Use Disorders and Poor Health in Early Adulthood.

Childhood and adolescent adversity have been shown to predict later mental and physical health outcomes. Understanding which aspects and developmental timings of adversity are important, and the mechanisms by which they have their impact may help guide intervention approaches. A large subset of adolescents (N = 457; Female 68.9 %) from the 10-year longitudinal Youth Emotion Project was examined to better understand the associations among childhood/adolescent adversity, substance use disorder, and later health quality. Adolescent (but not childhood) adversities were associated with poorer health in late adolescence/early adulthood, adolescent adversities were associated with subsequent onset of substance use disorder, and adolescent adversities continued to be associated with poorer health in late adolescence/early adulthood after accounting for the variance explained by substance use disorder onset. These associations were observed after statistically accounting for emotional disorders and socioeconomic status. Specific domains of adversity uniquely predicted substance use disorder and poorer health outcomes. In contrast with current recent research, our findings suggest the association between childhood/adolescent adversity and poorer health outcomes in late adolescence and emerging adulthood are not entirely accounted for by substance use disorder, suggesting efforts to curtail family-based adolescent adversity may have downstream health benefits.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord.

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.

Chronic and Episodic Stress in Children of Depressed Mothers.

The goal of this study was to examine chronic and episodic stress in children of mothers with and without a history of major depressive disorder (MDD) during the children's lives. Participants were 255 mothers selected according to their history of MDD (present vs. absent during child's life) and their children (age 8-14; 53% girls, 81% Caucasian). Mothers' and children's histories of MDD were assessed using diagnostic interviews, and their depressive symptoms were assessed via self-report measures. Children's levels of chronic and episodic stress were assessed using a semistructured contextual threat interview. Children of mothers with a history of recurrent MDD, compared to single MDD or no depression, experienced more chronic stress within several domains including peers, mother-child relations, and other family member relations as well as greater episodic dependent interpersonal stress. Each of these group differences was maintained after excluding children with a history of MDD themselves and controlling for their current depressive symptoms. However, only the group difference in chronic peer stress was maintained when controlling for mothers' current depression. The results suggest that children exposed to recurrent maternal MDD experience higher levels of both chronic and episodic stress, at least some of which they contribute to themselves (dependent interpersonal stress) and which is at least partially independent of the effects of children's depression. In addition, much of this stress is associated primarily with current depression in the mother, though it appears that chronic peer stress may remain elevated even after the remission of maternal depression.

The Impact of Asynchronous Pubertal Development on Depressive Symptoms in Adolescence and Emerging Adulthood Among Females.

Puberty is accompanied by numerous psychological and interpersonal challenges, including a dramatic rise in the prevalence of depression among girls. Pubertal timing has been identified as a potent predictor of depressive symptoms among females, but less is known about other features of puberty. The present study sought to address this gap in the literature by examining the effect of pubertal synchrony, the degree to which morphological indicators of puberty develop concurrently, on depressive symptoms in adolescence and emerging adulthood in a longitudinal sample. Among 355 female participants, asynchronous development at age 13 was associated with increased depressive symptoms at age 20, but not age 15. Additional analyses indicated that pubertal timing moderated the association between synchrony and depressive symptoms at age 20, such that girls who exhibited asynchronous development had the highest levels of depressive symptoms when they matured later than peers. Results provide initial empirical support for the role of pubertal synchrony in the development of depression among females and are discussed with regard to the biopsychosocial processes that may connect features of puberty with the long-term development of psychopathology.

Depressive episodes, symptoms, and trajectories in women recently diagnosed with breast cancer.

Depression carries serious psychosocial, physical, and economic consequences for cancer survivors. Study goals were to characterize patterns and predictors of depressive symptoms and major depressive episodes in recently diagnosed breast cancer patients. Consecutively recruited women (N = 460) completed a validated interview (CIDI) and questionnaire measure (CES-D) of depression within 4 months after invasive breast cancer diagnosis and at six additional assessments across 12 months. Outcomes were major depressive episodes, continuous symptom scores, and latent symptom trajectory classes. Across 12 months, 16.6 % of women met criteria for a major depressive episode. Unemployment predicted depressive episodes after other correlates were controlled. Distinct trajectory classes were apparent: an estimated 38 % of women had chronically elevated symptoms (High trajectory), 20 % recovered from elevated symptoms (Recovery), and 43 % had lower symptoms (Low and Very Low trajectories). Although 96 % of episodes occurred in the High or Recovery classes, 66 % of women in the High trajectory did not have an episode. Women in the Low (vs High) trajectory were more likely to be older, retired, more affluent, and have fewer comorbid diseases and briefer oncologic treatment. Women in the Recovery trajectory (vs High) were more likely to be married and more affluent and have fewer comorbid diseases. Assuming available therapeutic resources, assessment of both depressive symptoms and episodes over several months after diagnosis is important. Identification of patients at risk for persistently high depressive symptoms (e.g., younger, longer treatment course) opens targeted opportunities to prevent and promote rapid recovery from depression.

Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and IL1ß in youth.

AIMS: Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1ß (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. METHODS: Participants were 444 Australian youth (mean age=20.12) whose exposure to chronic stress in the past 6months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. RESULTS: In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1ß, previously associated with higher IL-1ß expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. CONCLUSION: Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to individual differences in depressive symptomatology following interpersonal stress exposure.

Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

A developmental pathway from early life stress to inflammation: the role of negative health behaviors.

Early life stressors are associated with elevated inflammation, a key physiological risk factor for disease. However, the mechanisms by which early stress leads to inflammation remain largely unknown. Using a longitudinal data set, we examined smoking, alcohol consumption, and body mass index (BMI) as health-behavior pathways by which early adversity might lead to inflammation during young adulthood. Contemporaneously measured early adversity predicted increased BMI and smoking but not alcohol consumption, and these effects were partially accounted for by chronic stress in young adulthood. Higher BMI in turn predicted higher levels of soluble tumor necrosis factor receptor type II (sTNF-RII) and C-reactive protein (CRP), and smoking predicted elevated sTNF-RII. These findings establish that early adversity contributes to inflammation in part through ongoing stress and maladaptive health behavior. Given that maladaptive health behaviors portend inflammation in young adulthood, they serve as promising targets for interventions designed to prevent the negative consequences of early adversity.

Does relational dysfunction mediate the association between anxiety disorders and later depression? Testing an interpersonal model of comorbidity.

BACKGROUND: Anxiety disorders tend to precede onset of comorbid depression. Several researchers have suggested a causal role for anxiety in promoting depressive episodes, but few studies have identified specific mechanisms. The current study proposes an interpersonal model of comorbidity, where anxiety disorders disrupt interpersonal functioning, which in turn elevates risk for depression. METHODS: At age 15 (T1), 815 adolescents oversampled for maternal depression completed diagnostic interviews, social chronic stress interviews, and self-report measures. At age 20 (T2), participants repeated all measures and reported on self-perceived interpersonal problems. At approximately age 23 (T3), a subset of participants (n = 475) completed a self-report depressive symptoms measure. RESULTS: Consistent with other samples, anxiety disorders largely preceded depressive disorders. Low sociability and interpersonal oversensitivity mediated the association between T1 social anxiety disorder and later depression (including T2 depressive diagnosis and T3 depressive symptoms), controlling for baseline. Interpersonal oversensitivity and social chronic stress similarly mediated the association between generalized anxiety disorder before age 15 and later depression. CONCLUSIONS: Interpersonal dysfunction may be one mechanism through which anxiety disorders promote later depression, contributing to high comorbidity rates.

Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by polymorphisms in serotonin transporter and corticotropin releasing hormone receptor genes in a 20-year longitudinal study.

Previous research supports gene-environment interactions for polymorphisms in the corticotropin hormone receptor 1 gene (CRHR1) and the serotonin transporter gene linked polymorphic region (5-HTTLPR) in predicting depression, but it has rarely considered genetic influences on stress sensitization processes, whereby early adversities (EA) increase depressive reactivity to proximal stressors later in life. The current study tested a gene-environment-environment interaction (G × E × E; specifically, gene-EA-proximal stress interaction) model of depression in a 20-year longitudinal study. Participants were assessed prospectively for EA up to age 5 and recent chronic stress and depressive symptoms at age 20 and genotyped for CRHR1 single nucleotide polymorphism rs110402 and 5-HTTLPR. EA predicted stronger associations between recent chronic stress and depression, and the effect was moderated by genes. CRHR1 A alleles and 5-HTTLPR short alleles were associated with greater stress sensitization (i.e., greater depressive reactivity to chronic stress for those also exposed to high levels of EA). The results are consistent with the notion that EA exposure results in neurobiological and cognitive-emotional consequences (e.g., altered hypothalamic-pituitary-adrenal axis functioning), leading to emotional distress in the face of recent stressors among those with certain genetic characteristics, although further research is needed to explore explanatory mechanisms.