Parenting Stress as a Mediator Between Childhood ADHD and Early Adult Female Outcomes

The purpose of this study is to examine the mediating role of parenting stress (both parental distress and stress due to dysfunctional interactions in the mother–daughter relationship [PSDI]) in the link between childhood attention-deficit/hyperactivity disorder (ADHD) status and several important young adult outcomes. The diverse sample comprised 140 girls with ADHD and 88 age- and ethnicity-matched comparisons, evaluated at ages 6–12 years and followed prospectively for five years (M age = 14.2) and 10 years (M age = 19.6). The PSDI experienced by a mother during her daughter's adolescence mediated the link between her daughter's childhood ADHD status and adult externalizing and internalizing symptoms. PSDI also mediated the link between ADHD status and young adult nonsuicidal self-injury and had an indirect effect in the relation between childhood ADHD and young adult depressive symptoms. The mediating role of PSDI with respect to internalizing symptoms and depressive symptoms remained in place even when covarying adolescent internalizing/depressive symptoms. Parenting stress, particularly related to maternal perceptions of dysfunctional interactions with adolescent daughters, serves as a key mediator in the association between childhood ADHD status and important domains of young adult functioning. Minimizing parenting stress and dysfunctional mother–daughter interactions during adolescence might reduce the risk of adverse adult outcomes for girls with ADHD.     

Reduced severity of posttraumatic stress disorder associated with Val allele of Val66Met polymorphism at brain‐derived neurotrophic factor gene among Chinese adolescents after Wenchuan earthquake

The aim of the present study was to longitudinally investigate the association of BDNF Val66Met with PTSD symptoms in Chinese Han adolescents who experienced the 2008 Wenchuan earthquake. Variants of BDNF Val66Met were identified by polymerase chain reaction‐restriction fragment length polymorphism analyses and verified by DNA sequencing. PTSD symptoms were assessed by the PTSD Checklist–Civilian Version (PCL‐C) among high school students at 6, 12, and 18 months after the earthquake. No differences of PTSD prevalence and PCL‐C scores were found between the Val/Val homozygotes and the Met allele carriers at 6, 12, and 18 months after the earthquake regardless of gender. Decreased PTSD prevalence was observed at 12 and 18 months when compared with that at 6 months after the earthquake regardless of gender and the genotype. Meanwhile, PCL‐C scores were decreased consecutively in the female subjects regardless of the genotypes. However, the scores at 18 months were lower when compared with those at 12 months in the male Val/Val homozygotes, but not in the male Met allele carriers. In addition, differences were found for the predictors of PCL‐C scores and PTSD prevalence between the Val/Val homozygotes and the Met allele carriers during follow‐up. These findings suggest that the association of BDNF Val66Met with PTSD is longitudinally different in Chinese Han adolescents after the 2008 Wenchuan earthquake. The Val allele may be associated with reduced PTSD severity in male adolescents in the later stage of PTSD rehabilitation during follow‐up.     

Age at onset of psychotic disorder: Cannabis,BDNF Val66Met,and sex‐specific models of gene–environment interaction

Discovering modifiable predictors for age at onset may help to identify predictors of transition to psychotic disorder in the “at‐risk mental state.” Inconsistent effects of sex, BDNF Val66Met (rs6265), and cannabis use on age of onset were previously reported. BDNF Val66Met and cannabis use before illness onset were retrospectively assessed in a sample of 585 patients with schizophrenia and their association with age at onset was evaluated. Cannabis use was significantly associated with earlier age at onset of psychotic disorder (AOP; average difference 2.7 years, P < 0.001), showing dose–response effects with higher frequency and earlier age at first use. There was a weak association between BDNF Val66Met genotype and AOP (difference 1.2 years; P = 0.050). No evidence was found for BDNF × cannabis interaction (interaction χ²(1) = 0.65, P = 0.420). However, a significant BDNF × cannabis × sex interaction was found (interaction χ²(1) = 4.99, P = 0.026). In female patients, cannabis use was associated with earlier AOP in BDNF Met‐carriers (difference 7 years), but not in Val/Val‐genotypes. In male patients, cannabis use was associated with earlier AOP irrespective of BDNF Val66Met genotype (difference 1.3 years). BDNF Val66Met genotype in the absence of cannabis use did not influence AOP, neither in female or male patients with psychotic disorder. Complex interactions between cannabis and BDNF may shape age at onset in female individuals at risk of psychotic disorder. No compelling evidence was found that BDNF genotype is associated with age at onset of psychotic disorder in the absence of cannabis use. © 2011 Wiley‐Liss, Inc.     

Hydrogen peroxide-induced Ca2+ responses in CNS pericytes

A single nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene Val66Met has been associated with depression. However, the relationship between this SNP and depression has been mixed, especially when comparing studies of child and adult depression. We examined whether Val66Met would predict depression differentially in mothers versus their daughters. We also examined whether rumination, the tendency to brood and repetitively think about negative information, might serve as a mediator in the path between genotype and depressive symptoms. Participants included 200 individuals (100 mother-daughter pairs) from a high-risk population. The BDNF Val66Met polymorphism was examined in DNA samples from the mothers and daughters, and measures of depressive symptoms and rumination were also obtained. Among the young adolescent girls (ages 10-14), the Val/Val genotype was associated with more depressive symptoms and higher rumination scores compared to the Val/Met genotype. Furthermore, rumination mediated the relationship between genotype and depressive symptoms. However, in the mothers with adult-onset depression the Val/Met genotype was associated with more depressive symptoms, and rumination again mediated the relationship between genotype and depression. Rumination may be an endophenotype in the pathway from the BDNF Val66Met polymorphism to depression. Future work should further explore this mechanism and pursue explanations for its effects at different times in development.     

Links Between the Mother–Adolescent and Father–Adolescent Relationships and Adolescent Depression: A Genetically Informed Study

This study examined the unique roles of support and conflict in the relationship with the mother and the father in predicting changes in adolescents’ depressive symptoms over a 1-year period. Potential moderating effects of genetic factors (Gene × Environment interaction) and sex were also investigated. This study utilized a design of twins raised in the same family, based on a sample of 121 monozygotic and 88 dizygotic same-sex twin pairs (418 individuals; 52.2% girls) assessed in Grade 8 (M = 14.09, SD = .29) and in Grade 9 (M = 15.07, SD = .26). Depressive symptoms and the parent–adolescent relationship quality were measured with self-report questionnaires. Multilevel regressions revealed that a lack of support in the father–adolescent relationship predicted increased depressive symptoms among all adolescents, whereas conflict in the father–adolescent relationship predicted increased depressive symptoms more strongly as adolescents’ genetic vulnerability for depressive symptoms increased. Moreover, a high level of support in the relationship with the mother predicted increased depressive symptoms in boys—but not girls—with a high genetic risk for such problems. In line with a diathesis-stress model of psychopathology, these findings suggest that relationship quality with both parents might impact girls’ and boys’ depressive symptoms but that these associations depend to some extent on adolescents’ genetic vulnerabilities.     

Chronic running-wheel exercise from adolescence leads to increased anxiety and depression-like phenotypes in adulthood in rats: Effects on stress markers and interaction with BDNF Val66Met genotype

Exercise has been shown to be beneficial in reducing symptoms of affective disorders and to increase the expression of brain-derived neurotrophic factor (BDNF). The BDNF Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety and depression. Male and female Val66Met rats were given access to running wheels from 3 weeks of age and compared to sedentary controls. Anxiety- and depression-like behaviors were measured in adulthood using the elevated plus maze (EPM), open field (OF), and forced swim test (FST). Expression of BDNF and a number of stress-related genes, the glucocorticoid receptor (Nr3c1), serum/glucocorticoid-regulated kinase 1 (Sgk1), and FK506 binding protein 51 (Fkbp5) in the hippocampus were also measured. Rats given access to running wheels developed high levels of voluntary exercise, decreased open-arm time on the EPM and center-field time in the OF, reduced overall exploratory activity in the open field, and increased immobility time in the FST with no differences between genotypes. Chronic exercise induced a significant increase in Bdnf mRNA and BDNF protein levels in the hippocampus with some of these effects being genotype specific. Exercise decreased the expression of Nr3c1 and Sgk1, but increased the expression of Fkbp5. These results suggest that chronic running-wheel exercise from adolescence increased anxiety and depression-like phenotypes in adulthood, independent of BDNF Val66Met genotype. Further studies are required to confirm that increased indices of anxiety-like behavior are independent from reduced overall locomotor activity.     

Effect of BDNF Val66Met Polymorphism on Normal Variability of Executive Functions

Associations of BDNF Val66Met polymorphism with such components of executive functions as verbal fluency, working memory, attention set shifting, and response inhibition were evaluated. A total of 401 healthy volunteers were genotyped. The effect of polymorphism on working memory during the counting test was detected. The test performance in heterozygotic carriers was much worse than in homozygotic ones. Individuals with the MetMet genotype demonstrated the best results, presumably due to molecular mechanisms compensating for the neuropeptide secretion deficiency.     

Brain‐derived neurotrophic factor Val66Met polymorphism and early life adversity affect hippocampal volume

The interaction between adverse life events during childhood and genetic factors is associated with a higher risk to develop major depressive disorder (MDD). One of the polymorphisms found to be associated with MDD is the Val66MET polymorphism of brain‐derived neurotrophic factor (BDNF). The aim of our two‐center study was to determine how the BDNF Val66Met polymorphism and childhood adversity affect the volumetric measures of the hippocampus in healthy individuals and people with MDD. In this two‐center study, 62 adult patients with MDD and 71 healthy matched controls underwent high‐resolution magnetic resonance imaging. We used manual tracing of the bilateral hippocampal structure with help of the software BRAINS2, assessed childhood adversity using the Childhood Trauma Questionnaire and genotyped Val66Met BDNF SNP (rs6265). MDD patients had smaller hippocampal volumes, both in the left and right hemispheres (F = 5.4, P = 0.022). We also found a significant interaction between BDNF allele and history of childhood adversity (F = 6.1, P = 0.015): Met allele carriers in our samples showed significantly smaller hippocampal volumes when they did have a history of childhood adversity, both in patients and controls. Our results highlight how relevant stress–gene interactions are for hippocampal volume reductions. Subjects exposed to early life adversity developed smaller hippocampal volumes when they carry the Met‐allele of the BDNF polymorphism. © 2013 Wiley Periodicals, Inc.     

Is BDNF‐Val66Met polymorphism associated with psychotic experiences and psychotic disorder outcome? Evidence from a 6 years prospective population‐based cohort study

There is little research on genetic risk for the extended psychosis phenotype ranging from psychotic experiences (PEs) to psychotic disorders (PDs). In this general population‐based prospective cohort study, the longitudinal associations between BDNF‐Val66Met polymorphism and the different levels of the extended psychosis phenotype were investigated. Addresses were contacted in a multistage clustered probability sampling frame covering 11 districts and 302 neighborhoods at baseline (n = 4011). A nested case‐control study (n = 366) recruited individuals with PEs and PDs as well as individuals with no psychotic symptoms. In this subgroup, blood sampling for genetic analysis and assessment of environmental exposures were carried out, followed by clinical re‐appraisal at follow‐up 6 years later (n = 254). The BDNF‐Val66Met polymorphism was significantly associated with the extended psychosis phenotype. The pattern of the association was that the BDNF‐Val66Met polymorphism impacted in a dose‐response but extra‐linear fashion, with stronger impact at the PD end of the extended psychosis phenotype. Associations were still significant after adjusting for sociodemographic factors and environmental exposures including life events, childhood adversity, socioeconomic status, urbanicity, and cannabis use. The BDNF‐Val66Met polymorphism may index susceptibility to expression of psychosis along a spectrum.     

Parenting as a Moderator of the Effects of Maternal Depressive Symptoms on Preadolescent Adjustment

The purpose of this study was to examine whether parenting moderated the association between maternal depressive symptoms and initial levels and growth of preadolescent internalizing and externalizing symptoms. This study used a community sample of preadolescent children (N = 214; 8–12 years old at Time 1), measuring maternal depressive symptoms and parenting at Time 1, and preadolescent internalizing and externalizing symptoms at each year for 3 years. After modeling latent growth curves of internalizing and externalizing symptoms, growth factors were conditioned on maternal depressive symptoms, positive (acceptance and consistent discipline) and negative (rejection and physical punishment) parenting, and the interactions of depression and parenting. Maternal rejection moderated the relation of maternal depression with internalizing symptoms, such that high rejection exacerbated the effects of maternal depressive symptoms on initial levels of preadolescent internalizing problems. There were no significant interactions predicting externalizing problems. The findings highlight how specific parenting behaviors may alter the way in which maternal depressive symptoms confer risk for behavior problems.     

Body Image Dissatisfaction and Anxiety Trajectories During Adolescence

The primary goal of this study was to examine the associations between baseline body image dissatisfaction (BID) and subsequent anxiety trajectories in a diverse, community sample of adolescent girls and boys. Participants were 581 adolescents (baseline age: M = 16.1, SD = 0.7; 58% female; 65% non-Hispanic White) from U.S. public high schools. Self-report questionnaires were administered during school at 3 annual assessment waves. Latent growth curve modeling examined the association between baseline BID and growth factors of anxiety disorder symptom trajectories. Covariates included baseline gender, age, race/ethnicity, parental education attainment, body mass index standard scores, and depressive symptoms. Higher BID at baseline was significantly associated with higher initial symptoms of generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD), and significant school avoidance (SSA; ps = .001–.04) but was unrelated to initial separation anxiety disorder (SEP) symptoms (p = .27). Higher baseline BID also was associated with attenuated decreases in SAD symptoms across time (p = .001). Among adolescents with low baseline anxiety symptoms only, higher BID was associated with more attenuated decreases in SAD symptoms (p = .01) and greater increases in PD symptoms (p = .02). BID was unrelated to changes in GAD, SEP, and SSA symptoms (ps = .11–.94). Findings suggest that BID is associated with concurrent symptoms of multiple anxiety disorders and may have a prospective link to SAD and PD symptoms during adolescence. As such, assessing body image issues may be important to assess when identifying adolescents at risk for exacerbated SAD and PD symptoms.     

Longitudinal pathways from early maternal depression to children’s dysregulated representations: a moderated mediation analysis of harsh parenting and gender

There is some evidence linking maternal depression, harsh parenting, and children’s internal representations of attachment, yet, longitudinal examinations of these relationships and differences in the developmental pathways between boys and girls are lacking. Moderated mediation growth curves were employed to examine harsh parenting as a mechanism underlying the link between maternal depression and children’s dysregulated representations using a nationally-representative, economically-vulnerable sample of mothers and their children (n = 575; 49% boys, 51% girls). Dysregulation representations were measured using the MacArthur Story Stem Battery at five years of age (M = 5.14, SD = 0.29). Harsh parenting mediated the association between early maternal depression and dysregulated representations for girls. Though initial harsh parenting was a significant mediator for boys, a stronger direct effect of maternal depression to dysregulated representations emerged over time. Results are discussed in terms of their implications for intervention efforts aimed at promoting early supportive parenting.     

Hippocampal volume and sensitivity to maternal aggressive behavior: a prospective study of adolescent depressive symptoms

It has been suggested that biological factors confer increased sensitivity to environmental influences on depressive symptoms during adolescence, a crucial time for the onset of depressive disorders. Given the critical role of the hippocampus in sensitivity to stress and processing of contextual aspects of the environment, investigation of its role in determining sensitivity to environmental context seems warranted. This study prospectively examined hippocampal volume as a measure of sensitivity to the influence of aggressive maternal behavior on change in depressive symptoms from early to midadolescence. The interaction between aggressive maternal behavior and hippocampal volume was found to predict change in depressive symptoms. Significant sex differences also emerged, whereby only for girls were larger bilateral hippocampal volumes more sensitive to the effects of maternal aggressive behavior, particularly with respect to experiencing the protective effects of low levels of maternal aggressiveness. These findings help elucidate the complex relationships between brain structure, environmental factors such as maternal parenting style, and sensitivity to (i.e., risk for, and protection from) the emergence of depression during this life stage. Given that family context risk factors are modifiable, our findings suggest the potential utility of targeted parenting interventions for the prevention and treatment of adolescent depressive disorder.     

Examining the Pathologic Adaptation Model of Community Violence Exposure in Male Adolescents of Color

The current study examined a model of desensitization to community violence exposure—the pathologic adaptation model—in male adolescents of color. The current study included 285 African American (61%) and Latino (39%) male adolescents (W1 M age = 12.41) from the Chicago Youth Development Study to examine the longitudinal associations between community violence exposure, depressive symptoms, and violent behavior. Consistent with the pathologic adaptation model, results indicated a linear, positive association between community violence exposure in middle adolescence and violent behavior in late adolescence, as well as a curvilinear association between community violence exposure in middle adolescence and depressive symptoms in late adolescence, suggesting emotional desensitization. Further, these effects were specific to cognitive-affective symptoms of depression and not somatic symptoms. Emotional desensitization outcomes, as assessed by depressive symptoms, can occur in male adolescents of color exposed to community violence and these effects extend from middle adolescence to late adolescence.     

Joint Contributions of Negative Emotionality,Positive Emotionality,and Effortful Control on Depressive Symptoms in Youth

From a clinical developmental perspective, temperament has been shown to confer vulnerability to depression among youth. High negative emotionality (NE), low positive emotionality (PE), and low effortful control (EC) have repeatedly been independently associated with youth depressive symptoms. However, far less research has examined the joint contributions of NE, PE, and EC on such symptoms. The present study builds upon previous research by examining how NE, PE, and EC jointly predict change in depressive symptoms over time among 211 youngsters (7–14 years, M = 10.7, SD = 1.81) who participated in an 8-month prospective study. Self-reported temperament and symptoms were assessed at baseline; self-reported symptoms were measured again at follow-up. Results suggest that all 3 temperamental traits need to be considered jointly in predicting change in depressive symptoms. Furthermore, results provide further support for the “best two out of three” principle. Surprisingly, results reveal that high EC might be maladaptive in the context of high emotional reactivity. Last, results show that the combination of high NE and low EC could be a possible pathway to the development of symptoms. The current study clarified how NE, PE, and EC may jointly confer risk—or protection for developing depressive symptoms during adolescence. The results highlight the need of taking into account all three temperamental traits in order to provide a more nuanced understanding of the risk for developing depressive symptoms at an early stage, as well as to provide customized care targeting temperamental vulnerability in depressed youth.     

Associations Between Anxious and Depressive Symptoms and the Recognition of Vocal Socioemotional Expressions in Youth

The current study examined the associations between internalizing symptoms and adolescents’ recognition of vocal socioemotional expressions produced by youth. Fifty-seven youth (8–17 years old, M = 12.62, SD = 2.66; 29 anxious, 28 nonanxious; 32 female, 25 male) were asked to identify the intended expression in auditory recordings of youth’s portrayals of basic emotions and social attitudes. Recognition accuracy increased with age, suggesting that the ability to recognize vocal affect continues to develop into adolescence. Anxiety symptoms were not associated with recognition ability, but youth’s depressive symptoms were related to poorer identification of anger and happiness. Youth experiencing symptoms of depression may be likely to misinterpret vocal expressions of happiness and anger.     

Depressive Symptoms and Alcohol Use are Genetically and Environmentally Correlated Across Adolescence

Depressive symptoms and alcohol use are frequently positively associated during adolescence. This study aimed to assess the heritability of each phenotype across adolescence; to assess potential shared liabilities; to examine changes in the nature of shared liabilities across adolescence; and to investigate potential causal relationships between depressive symptoms and alcohol use. We studied a longitudinally assessed sample of adolescent Finnish twins (N = 1,282) to test hypotheses about genetic and environmental influences on these phenotypes within and across ages, using data from assessments at ages 12, 14, and 17.5 years. The heritability of depressive symptoms is consistent across adolescence (~40–50%), with contributions from common and unique environmental factors. The heritability of alcohol use varies across time (a² = .25–.44), and age 14 alcohol use is heavily influenced by shared environmental factors. Genetic attenuation and innovation were observed across waves. Modest to moderate genetic (r_A = .26–.59) and environmental (r_C = .30–.63) correlations between phenotypes exist at all ages, but decrease over time. Tests for causal relationships between traits differed across ages and sexes. Intrapair MZ difference tests provided evidence for reciprocal causation in girls at ages 14 and 17.5. Formal causal models suggested significant causal relationships between the variables in both boys and girls. The association between depressive symptoms and alcohol use during adolescence is likely due to a combination of shared genetic and environmental influences and causal influences. These influences are also temporally dynamic, complicating efforts to understand factors contributing to the relationship between these outcomes.     

Association between BDNF Polymorphism and Depressive Symptoms in Patients Newly Diagnosed with Type 2 Diabetes Mellitus

PurposeLittle is known about the relationship between brain-derived neurotrophic factor (BDNF) gene polymorphisms and psychiatric symptoms in diabetes patients. We investigated the effects of BDNF Val/66/Met polymorphism, glucose status, psychological susceptibility, and resilience on anxiety and depression symptoms in patients newly diagnosed with type 2 diabetes mellitus (T2DM).Materials and MethodsWe examined biochemical factors and BDNF polymorphism in 89 patients who were newly diagnosed with T2DM. Psychiatric symptoms were investigated with the Hospital Anxiety and Depression Scale (HADS), and the Connor-Davidson Resilience Scale (CD-RISC) and Impact of Event Scale (IES) were used to assess psychological resilience and susceptibility to psychological distress, respectively. Logistic regression analyses were conducted to investigate factors associated with psychiatric symptoms.ResultsWe determined that 62 patients (70%) were Met-carriers. No significant differences were found between the Val/Val homozygous and Met-carrier groups regarding age, sex, body mass index, and clinical factors related to glycemic control and lipid profiles. HADS-anxiety and HADS-depression scores and IES factor scores were higher in the Met-carrier than the Val/Val homozygous group. Hemoglobin A1c (HbA1c) level was significantly inversely correlated with the severity of depressive symptoms. Resilience factors showed significant inverse correlations, and IES factors showed positive correlations with depressive symptom severity. In the logistic regression analysis model, depressive symptoms were significantly associated with HbA1c and BDNF polymorphism, whereas only the hyperarousal factor of the IES scale was associated with anxiety.ConclusionDepressive symptoms are associated with the presence of the Met-carriers and lower HbA1c in patients newly diagnosed with T2DM.     

The Relation of Childhood Maltreatment to Psychotic Symptoms in Adolescents and Young Adults With Depression

This study examined the relation between a history of maltreatment and the presence of psychotic symptoms in a community sample of adolescents and young adults with major depressive disorder. One hundred and twenty-nine depressed adolescents and young adults (M = 16.02 years, 77% female, 92% White) were recruited through community advertisement and clinician referral. Clinical diagnoses and psychotic symptoms (i.e., hallucinations and delusions) were assessed using a structured diagnostic interview. Childhood maltreatment was assessed using a contextual interview and standardized rating system. Logistic regression analyses examined the relation between childhood maltreatment and psychotic symptoms. As hypothesized, individuals with psychotic symptoms were significantly more likely to report a history of severe sexual maltreatment than those without psychotic symptoms (Wald = 5.44, odds ratio = 3.86, p = .020), 95% confidence interval [1.24, 12.01]. Further, those with psychotic symptoms were more likely to report being the victims of more than one type of maltreatment than those without, χ²(2) = 6.66, p = .036 (? = .23; 40% vs. 16%). Results held upon adjusting for overall level of depression symptoms. A history of severe sexual maltreatment is related to a severe presentation of major depressive disorder even in the initial onset of the syndrome in adolescence and young adulthood. These findings underscore the importance of early assessment of both depression and maltreatment history to implement interventions that have the potential to prevent the emergence of psychotic psychopathology in young people at risk.     

Changes in PTSD and Depression During Prolonged Exposure and Client-Centered Therapy for PTSD in Adolescents

Depressive symptoms are common among individuals with posttraumatic stress disorder (PTSD). Prolonged exposure therapy (PE) for PTSD has been found to alleviate both PTSD and depressive symptoms, but relatively little is known about the pattern of PTSD and depressive symptom change during treatment. This study aimed to investigate the relationship between changes in PTSD and depression during PE for adolescent (PE-A) and client-centered therapy (CCT). The moderating role of PE-A versus CCT and the possible differences across symptom clusters of PTSD were also examined. Participants were 61 female adolescents with sexual-assault-related PTSD randomized to PE-A (n = 31) or CCT (n = 30). Participants completed the Beck Depression Inventory and the Child PTSD Symptom Scale at pre-, mid-, and posttreatment and before each treatment session. Multilevel mediation analysis indicated a reciprocal but asymmetrical relationship between changes in PTSD and depression during treatment in the overall sample. Moderated mediation analysis showed that the reciprocal relation was observed only during PE-A. Reductions in PTSD led to reductions in depression to a greater extent (48.7%), 95% confidence interval [30.2, 67.2], than vice versa (22.0%), [10.6, 33.4]. For participants receiving CCT, reduction in PTSD led to reductions in depression (31.6%), [11.8, 51.4], but not vice versa (7.4%), [?7.1, 21.9]. The reciprocal relationship between PTSD and depression was also observed across different symptoms clusters of PTSD. Our findings suggest that changes in PTSD led to changes in depressive symptoms to a greater extent than vice versa across PE-A and CCT.