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What distinguishes vulnerability and resilience to posttraumatic stress disorder (PTSD) remains unclear. Levering traumatic experiences reporting, genetic data, and electronic health records (EHR), we investigated and predicted the clinical comorbidities (co-phenome) of PTSD vulnerability and resilience in the UK Biobank (UKB) and All of Us Research Program (AoU), respectively. In 60,354 trauma-exposed UKB participants, we defined PTSD vulnerability and resilience considering PTSD symptoms, trauma burden, and polygenic risk scores. EHR-based phenome-wide association studies (PheWAS) were conducted to dissect the co-phenomes of PTSD vulnerability and resilience. Significant diagnostic endpoints were applied as weights, yielding a phenotypic risk score (PheRS) to conduct PheWAS of PTSD vulnerability and resilience PheRS in up to 95,761 AoU participants. EHR-based PheWAS revealed three significant phenotypes positively associated with PTSD vulnerability (top association "Sleep disorders") and five outcomes inversely associated with PTSD resilience (top association "Irritable Bowel Syndrome"). In the AoU cohort, PheRS analysis showed a partial inverse relationship between vulnerability and resilience with distinct comorbid associations. While PheRS vulnerability associations were linked to multiple phenotypes, PheRS resilience showed inverse relationships with eye conditions. Our study unveils phenotypic differences in PTSD vulnerability and resilience, highlighting that these concepts are not simply the absence and presence of PTSD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Polimanti received a research grant from Alkermes for the present study. Drs. Polimanti and Gelernter received honorariums for editorial work in the journal Complex Psychiatry. The other authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Suicide is a leading cause of death worldwide. Whereas some studies have suggested that a direct measure of common genetic liability for suicide attempts (SA), captured by a polygenic risk score for SA (SA-PRS), explains risk independent of parental history, further confirmation would be useful. Even more unsettled is the extent to which SA-PRS is associated with lifetime non-suicidal self-injury (NSSI)., Methods: We used summary statistics from the largest available GWAS study of SA to generate SA-PRS for two non-overlapping cohorts of soldiers of European ancestry. These were tested in multivariable models that included parental major depressive disorder (MDD) and parental SA., Results: In the first cohort, 417 (6.3 %) of 6573 soldiers reported lifetime SA and 1195 (18.2 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.26, 95%CI:1.13-1.39, p < 0.001] per standardized unit SA-PRS]. In the second cohort, 204 (4.2 %) of 4900 soldiers reported lifetime SA, and 299 (6.1 %) reported lifetime NSSI. In a multivariable model that included parental history of MDD and parental history of SA, SA-PRS remained significantly associated with lifetime SA [aOR = 1.20, 95%CI:1.04-1.38, p = 0.014]. A combined analysis of both cohorts yielded similar results. In neither cohort or in the combined analysis was SA-PRS significantly associated with NSSI., Conclusions: PRS for SA conveys information about likelihood of lifetime SA (but not NSSI, demonstrating specificity), independent of self-reported parental history of MDD and parental history of SA., Limitations: At present, the magnitude of effects is small and would not be immediately useful for clinical decision-making or risk-stratified prevention initiatives, but this may be expected to improve with further iterations. Also critical will be the extension of these findings to more diverse populations., Competing Interests: Declaration of competing interest Dr. Kessler has in the past three years received support for his epidemiological studies from Sanofi Aventis; and was a consultant for Datastat, Inc., Sage Pharmaceuticals, and Takeda. Dr. Stein has in the past three years been a paid consultant for Aptinyx, BigHealth, Biogen, Bionomics, Boehringer-Ingelheim, Cerevel Therapeutics, EmpowerPharm, Engrail Therapeutics, Genentech/Roche, GW Pharma, Janssen, Jazz Pharmaceuticals, Otsuka, Oxeia Biopharmaceuticals, PureTech Health, and Sage Therapeutics. Dr. Smoller is a member of the Scientific Advisory Board of Sensorium Therapeutics (with equity), and has received grant support from Biogen, Inc., is PI of a collaborative study of the genetics of depression and bipolar disorder sponsored by 23andMe for which 23andMe provides analysis time as in-kind support but no payments. The remaining authors have no disclosures., (Published by Elsevier B.V.)

Background: Many servicemembers experience difficulties transitioning from military to civilian life. We examined whether changes in mental health observed during active duty were associated with indices of post-military adjustment., Methods: Survey data from the multi-wave Army STARRS Pre/Post Deployment Study (PPDS; conducted 2012-2014) were linked to follow-up data from wave 1 of the STARRS Longitudinal Study (STARRS-LS1; conducted 2016-2018). Empirical Bayes estimates of intercepts and slopes of posttraumatic stress, problematic anger, and depressive symptoms during the PPDS were extracted from mixed-effects growth models and evaluated as predictors of life stress among 1080 participants who had separated or retired from the Army at STARRS-LS1; and of job satisfaction among 586 veterans who were employed at STARRS-LS1., Results: Higher average levels and larger increases in posttraumatic stress, anger, and depression over the deployment period were each associated with increased stress and (in the case of anger and depression) reduced job satisfaction. Posttraumatic stress and anger slopes were associated with overall stress (b = 5.60, p < 0.01 and b = 15.64, p = 0.04, respectively) and relationship stress (b = 5.50, p = 0.01 and b = 22.86, p = 0.01, respectively) beyond the average levels of those symptoms., Limitations: Some transition-related difficulties may have resolved before outcome assessment; some measures were not previously validated., Conclusions: Larger increases in posttraumatic stress and anger over a deployment period were associated with increased stress after leaving the Army, even after controlling for average symptom levels during the same period. Monitoring changes in mental health during active duty may help identify personnel who need additional support to facilitate the military-to-civilian transition., Competing Interests: Declaration of competing interest In the past 3 years, Dr. Kessler was a consultant for Cambridge Health Alliance, Canandaigua VA Medical Center, Holmusk, Partners Healthcare, Inc., RallyPoint Networks, Inc., and Sage Therapeutics. He has stock options in Cerebral Inc., Mirah, PYM, and Roga Sciences. In the past 3 years, Dr. Stein has received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sumitomo Pharma, and Roche/Genentech. Dr. Stein has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He has also received research support from NIH, Department of Veterans Affairs, and the Department of Defense. He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America. The other authors have no known conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Potentially traumatic events (PTEs) are common and associated with detrimental outcomes over the life-course. Previous studies exploring the causes and consequences of PTE-exposure profiles are often from high-income settings and fail to explore the implications of sample selection (i.e., population-representative versus PTE-restricted)., Methods: Among individuals in the Nepal Chitwan Valley Family Study, latent class analyses (LCA) were performed on 11 self-reported PTEs collected by the Nepali version of the World Mental Health Consortium's Composite International Diagnostic Interview 3.0 from 2016 to 2018, in a population-representative sample (N = 10,714), including a PTE-restricted subsample (N = 9183). Multinomial logistic regressions explored relationships between sociodemographic factors and class membership. Logistic regressions assessed relationships between class membership and psychiatric outcomes., Results: On average, individuals were exposed to 2 PTEs in their lifetime. A five-class solution showed optimal fit for both samples; however, specific classes were distinct. No single sociodemographic factor was universally associated with PTE class membership in the population-representative sample; while several factors (e.g., age, age at incident PTE, education, marital status, and migration) were consistently associated with class membership in the PTE-subsample. PTE class membership differentiated psychiatric outcomes in the population-representative sample more than the PTE-subsample., Limitations: Primary limitations are related to the generalizability to high-income settings, debate on LCA model fit statistic usage for final class selection, and cross-sectional nature of data collection., Conclusions: Although population-representative samples provide information applicable to large-scale, population-based programming and policy, PTE-subsample analyses may provide additional nuance in PTE profiles and their consequences, important for specialized prevention efforts., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Although major depressive disorder (MDD) has been associated with volumetric abnormalities in the amygdala, studies investigating the association between structural alterations of the amygdala and depression have yielded varying results. Since the amygdala comprises several subregions, it is difficult to detect subtle regional changes by measuring the total amygdala volume. This study aimed to examine the volume in each amygdala subregion in adults with and without a diagnosis of MDD., Methods: A total of 147 participants with a current history of major depression and 144 healthy participants ranging in age from 19 to 64 years underwent 3T magnetic resonance imaging scanning. Automatic segmentation of the nine nuclei of the amygdala was performed using FreeSurfer. One-way analysis of covariance, with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates, was performed to analyze volume differences., Results: Patients with MDD had significantly lower volumes of the entire amygdala and subregions, including the lateral nucleus and anterior amygdaloid area, than healthy volunteers (HCs). There were no significant associations between subregion volumes and antidepressant use, illness duration, or depression severity., Limitations: Our cross-sectional design cannot provide a causal relationship between the volume change in the amygdala subregion and the risk of MDD., Conclusion: Our findings suggest that specific amygdala subregions are more susceptible to volumetric alterations in patients with MDD than in HCs. These findings may advance our understanding of the neuroanatomic basis on MDD., (Copyright © 2021. Published by Elsevier B.V.)

Background: Long working hours can be a risk factor for poor mental health; however, little is known about the potential factors moderating their relation. This study investigates the association between working hours and depressive symptoms, and explores the potential moderating effect of gender, income level, and job status on this association using a nationally representative sample of working population in South Korea., Methods: Data of 7,082 workers aged 19 years or above were obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted in 2014, 2016, and 2018 in South Korea. Working hours were categorized into 35-39, 40, 41-52, 53-68, and ≥69 hours/week. Depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9)., Results: Individuals working ≥69 hours/week were more likely to have moderate to severe depressive symptoms compared to those working 40 hours/week. The association between longer working hours and depressive symptoms was especially prominent in female workers, standard wage workers, and workers with low income levels. We observed significant partial mediation pathways between working hours and PHQ-9 scores through both perceived usual stress level and self-rated health in the total sample., Limitations: The cross-sectional design of the study limits causal interpretation of the findings., Conclusion: Working longer than the legal upper limit of 52 hours/week puts workers at a greater risk for depression. Females, low-income workers, and wage workers are more vulnerable to the negative consequences of long working hours on mental health., (Copyright © 2021. Published by Elsevier B.V.)

Background: There have been considerable recent advances in understanding the genetic architecture of psychiatric disorders as well as the underlying neurocircuitry. However, there is little work on the concordance of genetic variations that increase risk for cross-disorder vulnerability, and those that influence subcortical brain structures. We undertook a genome-wide investigation of the genetic overlap between cross-disorder vulnerability to psychiatric disorders (p-factor) and subcortical brain structures., Methods: Summary statistics were obtained from the PGC cross-disorder genome-wide association study (GWAS) (N case = 232,964, N control = 494,162) and the CHARGE-ENIGMA subcortical brain volumes GWAS (N=38,851). SNP effect concordance analysis (SECA) was used to assess pleiotropy and concordance. Linkage Disequilibrium (LD) Score Regression and ρ-HESS were used to assess genetic correlation and conditional false discovery (cFDR) was used to identify variants associated with p-factor, conditional on the variants association with subcortical brain volumes., Results: Evidence of global pleiotropy between p-factor and all subcortical brain regions was observed. Risk variants for p-factor correlated negatively with brainstem. A total of 787 LD-independent variants were significantly associated with p-factor when conditioned on the subcortical GWAS results. Gene set enrichment analysis of these variants implicated actin binding and neuronal regulation., Limitations: SECA could be biased due to the potential presence of overlapping study participants in the p-factor and subcortical GWASs., Conclusion: Findings of genome-wide pleiotropy and possible concordance between genetic variants that contribute to p-factor and smaller brainstem volumes, are consistent with previous work. cFDR results highlight actin binding and neuron regulation as key underlying mechanisms. Further fine-grained delineation of these mechanisms is needed to advance the field., (Copyright © 2020. Published by Elsevier B.V.)

Background: Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs)., Methods: Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates., Results: The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions., Limitations: Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD., Conclusions: We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD., Competing Interests: Declaration of Competing Interest The authors have no potential or actual conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults., Methods: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood., Results: Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p < 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p < 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder., Conclusion: In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder., Competing Interests: Declaration of Competing Interest None, (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Although structural alterations have been reported in patients with major depressive disorder (MDD), very few studies have compared the shape alterations of the subcortical regions between drug-naïve MDD patients and healthy controls (HCs). Therefore, we investigated and compared the subcortical shape alterations and volumetric changes between drug-naïve MDD patients and HCs in this study., Methods: This study included 45 drug-naïve MDD patients and 83 HCs, who underwent three-dimensional (3-D) T1-weighted structural magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nuclei accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. SVA revealed regional contractions of the thalamus (bilateral medial and lateral nuclei) and right caudate nucleus (medial wall and anterosuperior areas) in the drug-naïve MDD patients when compared to HCs RESULTS: In volume analysis, the drug-naïve MDD patients showed a significant decrease in the volume of bilateral thalami compared with HCs (after Bonferroni correction p < 0.003). We identified morphometric contractions in bilateral thalami and right caudate nucleus in the drug-naïve MDD patients (p < 0.05)., Conclusions: The present study implied that with cortical shape changes, the subcortical brain alterations could contribute to emotional dysregulation in the drug-naïve MDD patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Subthreshold hypomania is defined as a distinct period of elevated, expansive or irritable mood lasting for at least four days, but insufficient to fulfill the criteria of hypomania. This study aimed to investigate the association between suicidality and subthreshold hypomania in subjects with and without major depressive disorder (MDD)., Methods: Face-to-face interviews were completed for 12,526 adults, randomly selected through a one-person-per-household method, using the Korean version of the Composite International Diagnostic Interview (K-CIDI) and a questionnaire relative to lifetime suicide attempts (LSA)., Results: Of the 12,526 participants, 11,701 did not have MDD, and 825 were diagnosed with MDD. The MDD with subthreshold hypomania group (n = 72) revealed significantly higher rates of LSA and post-traumatic stress disorder (PTSD) than those without (n = 753). Compared to the no MDD without subthreshold hypomania group (n = 11,571), the no MDD with subthreshold hypomania group (n = 130) showed a significantly higher prevalence of suicidality and comorbid conditions. In multivariate logistic regression analyses of depressive symptoms, subthreshold hypomania was significantly associated with morning worsening of mood. The MDD with subthreshold hypomania group was significantly associated with LSA (AOR=16.82, 95% CI 9.81-28.83, p< 0.001), compared to the no MDD group without subthreshold hypomania. Compared to the MDD without subthreshold hypomania group, the MDD with subthreshold hypomania group revealed a significant association with LSA (AOR=2.08, 95% CI 1.20-3.62, p< 0.001)., Conclusions: A history of subthreshold hypomania doubled the risk of LSA in patients with MDD compared to those without subthreshold hypomania., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Heart Rate Variability (HRV) parameters have been used to evaluate the autonomic nervous system. We hypothesized that patients with major depressive disorder (MDD) and panic disorder (PD) showed different HRV profiles compared to healthy controls. We also hypothesized that we could predict the responder groups in the MDD and PD patients, using differences in HRV indices between the stress and rest phases., Methods: 28 MDD patients and 29 PD patients were followed for 12 weeks, and we also followed 39 healthy control subjects. We measured HRV parameters at the rest, stress, and recovery phases., Results: Patients with MDD and PD demonstrated lower pNN50 than controls during the stress (F = 7.49, p = 0.001), and recovery phases (F = 9.43, p = 0.0001). Patients with MDD and PD also showed higher LF/HF ratio than controls during the stress phase (F = 6.15, p = 0.002). Responders in the PD group presented a lower level of LF/HF ratio during the stress phase compared to non-responders (F = 10.14, p = 0.002), while responders in the MDD group showed a lower level of heart rate during all three phases, compared to non-responders. Additionally, we could predict treatment response in patients with MDD using ΔLF/HF ratio (OR: 1.33, 95% CI = 1.07-1.65, p = 0.011) and ΔpNN50 (OR: 1.49, 95% CI 1.09-1.77, p = 0.014)., Conclusion: The changes of HRV parameters of pNN50 and LF/HF ratio between the stress and recovery phase may be clinical markers of predictors of treatment responsiveness in MDD and PD patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depressive disorder (MDD). Outpatients diagnosed with MDD (n = 199) underwent psychological evaluation, and were followed up with a phone interview after 6 months, using the Patient Health Questionnaire (PHQ-9). At 6-month follow-up, 59 out of 199 patients with MDD were still depressed (29.5%), as shown by scores ≥ 10 on the PHQ-9. The depressed group at follow-up showed significantly higher anxiety and suicidality levels at baseline than the non-depressed group at follow-up. Among the complete blood counts, lipid profiles, and hormone levels, adrenocorticotropic hormone (ACTH) was the only parameter that was significantly increased in the still depressed group. Levels higher than 40 pg/mL of ACTH at baseline were associated with higher depression scores at follow-up. Multiple linear regression analyses revealed that ACTH and cortisol predicted depression scores at follow-up, after controlling for baseline depression scores. Increased ACTH level at baseline may predict ongoing symptoms and severity of depression at follow-up, suggesting the role of dysfunctional HPA axis in MDD prognosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Regardless of categorical diagnosis, many psychiatric patients suffer from sudden attack of fear or intense anxiety. In this study, we defined anxiety attacks to refer to these phenomena and investigated their association with depression and suicide attempts. A total of 12,532 adults randomly selected population through the one-person-per-household method completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI). A total of 5.88% reported to have experienced anxiety attacks. Among them, 46.5% reported to have experienced anxiety attacks without life-threatening situations. 'Anxiety attacks' group reported more suicidal ideation, plan, and attempts, which were even higher frequencies in 'anxiety attacks without life-threatening situations' group than 'anxiety attacks only with life-threatening situations' group and showed stronger association with lifetime suicide attempts when it had comorbid major depressive disorder (MDD) (AOR = 9.69, 95%CI 5.90-15.90), compared with 'never' group. There was no association between each symptom of patients with anxiety attacks and their lifetime suicide attempt. In conclusion, the finding suggests that there are as many individuals who experience anxiety attacks without life-threatening situations as those with life-threatening situations. And anxiety attacks appear to be relevant to an increased risk of suicide attempt, especially without life-threatening situations and with comorbid MDD., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Alcohol-induced disinhibition (AID) is defined as a "loss of restraint over some form of behavior after drinking alcohol regardless of its amount". Although many previous studies have investigated on alcohol use disorder and suicide attempt, few studies have focused on AID and suicide., Methods: A total of 9461 adults who had a history of drinking completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) with the Suicide Module, and Barratt Impulsiveness Scale 11 (BIS-11). In this study, we defined the AID group as those who had been involved with the two antisocial behaviors, including fights, being arrested or dangerous driving, according to the K-CIDI., Results: Among 9461 subjects, 564 were classified as the AID group (5.96%). The AID group had a significantly higher number of lifetime suicidal ideation, plan, attempt, and multiple attempts, and higher BIS-11 scores than non-AID group. The total scores of BIS-11 of the AID group reported the highest score compared with other psychiatric disorders. The AID group experienced more frequently three types of alcohol withdrawal symptoms, including nervousness, heart beating fast, and feeling weak. Compared with subjects without both AID and MDD, subjects with both AID and MDD showed significant association with a lifetime suicide attempt (AOR = 6.86, p < 0.001) and showed stronger association with multiple attempts (AOR = 10.38, p < 0.001)., Conclusion: AID was associated with suicide attempt and impulsivity, and the both AID and MDD showed much stronger association with lifetime suicide attempt and multiple attempts., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Women who have experienced childhood trauma may be at risk for postpartum depression, increasing the likelihood of negative outcomes among their children. Predictive pathways from maternal childhood trauma to child outcomes, as mediated by postpartum depression, require investigation., Methods: A longitudinal sample of South African women (N=150) was followed through pregnancy and postpartum. Measures included maternal trauma history reported during pregnancy; postpartum depression through six months; and maternal-infant bonding, infant development, and infant physical growth at one year. Structural equation models tested postpartum depression as a mediator between maternal experiences of childhood trauma and children's outcomes. A subset of women (N=33) also participated in a lab-based emotional Stroop paradigm, and their responses to fearful stimuli at six weeks were explored as a potential mechanism linking maternal childhood trauma, postpartum depression, and child outcomes., Results: Women with childhood trauma experienced greater depressive symptoms through six months postpartum, which then predicted negative child outcomes at one year. Mediating effects of postpartum depression were significant, and persisted for maternal-infant bonding and infant growth after controlling for covariates and antenatal distress. Maternal avoidance of fearful stimuli emerged as a potential affective mechanism., Limitations: Limitations included modest sample size, self-report measures, and unmeasured potential confounders., Conclusions: Findings suggest a mediating role of postpartum depression in the intergenerational transmission of negative outcomes. Perinatal interventions that address maternal trauma histories and depression, as well as underlying affective mechanisms, may help interrupt cycles of disadvantage, particularly in high-trauma settings such as South Africa., (Copyright © 2017. Published by Elsevier B.V.)