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Background: Stressful life events are more likely to trigger depression among individuals exposed to childhood adversity. However, the mechanisms underlying this stress sensitization remain largely unknown. Any such mechanism must be altered by childhood adversity and interact with recent stressful life events, magnifying their association with depression., Aim: This study investigated whether reduced hippocampal and amygdala volume are potential mechanisms underlying stress sensitization following childhood violence exposure., Method: A sample of 149 youth (aged 8-17 years), with (N = 75) and without (N = 74) exposure to physical abuse, sexual abuse, or domestic violence participated. Participants completed a structural MRI scan and assessments of depression. Approximately 2 years later, stressful life events were assessed along with depression symptoms in 120 participants (57 violence exposed)., Results: Childhood violence exposure was associated with smaller hippocampal and amygdala volume. Stressful life events occurring during the follow-up period predicted worsening depression over time, and this association was magnified among those with smaller hippocampal and amygdala volumes. Significant moderated mediation models revealed the indirect effects of violence exposure on increasing depression over time through hippocampal and amygdala volumes, particularly among youths who experienced more stressful life events., Conclusions: These results provide evidence for reduced hippocampal and amygdala volume as potential mechanisms of stress sensitization to depression following exposure to violence. More broadly, these patterns suggest that hippocampal and amygdala-mediated emotional and cognitive processes may confer vulnerability to stressful life events among children who have experienced violence., (© 2020 Wiley Periodicals LLC.)

Background: Disruptions in emotion regulation are a transdiagnostic risk factor for psychopathology. However, scant research has examined whether emotion regulation strategies are related to the onset of posttraumatic stress disorder (PTSD) symptoms among youths exposed to trauma. We investigated whether pretrauma emotion regulation strategies prospectively predicted PTSD symptom onset after the 2013 Boston Marathon terrorist attack among adolescents and whether these associations were moderated by the degree of exposure to media coverage of the attack., Methods: A sample of 78 Boston-area adolescents (mean age = 16.72 years, 65% female) who previously participated in studies assessing emotion regulation and psychopathology were recruited following the terrorist attack. Within 4 weeks of the attack, we assessed self-reported PTSD symptoms and attack-related media exposure via an online survey. We examined the association of pretrauma emotion regulation strategies with PTSD symptom onset after adjustment for pretrauma internalizing symptoms and violence exposure., Results: Greater pretrauma engagement in rumination predicted onset of PTSD symptoms following the attack. Adolescents who engaged in catastrophizing also had greater PTSD symptoms postattack, but only when exposed to high levels of media coverage of the attacks; the same pattern was observed for adolescents who engaged in low levels of cognitive reappraisal., Conclusions: Engagement in specific emotion regulation strategies prior to a traumatic event predicts the onset of PTSD symptoms among youths exposed to trauma, extending transdiagnostic models of emotion regulation to encompass trauma-related psychopathology in children and adolescents., (© 2016 Wiley Periodicals, Inc.)

Background: Evidence suggests that impulsive aggression and explosive anger are common among individuals with anxiety disorders; yet, the influence of intermittent explosive disorder (IED) on the onset, course, consequences, and patterns of comorbidity among those with anxiety disorders is unknown., Methods: Data were drawn from the National Comorbidity Survey Replication (N = 9,282) and Adolescent Supplement (N = 9,632), nationally representative surveys conducted between 2001 and 2004. Diagnoses were based on structured lay-administered interviews. Lifetime diagnoses were assessed with structured instruments. Outcomes included comorbidity, functional and role impairment, and treatment utilization., Results: Adolescents with a lifetime anxiety disorder had a higher prevalence of a lifetime anger attacks (68.5%) and IED (22.9%) than adolescents without a lifetime anxiety disorder (48.6 and 7.8%, respectively), especially social phobia and panic disorders. Similar elevation was found for adults. Age of onset and course of anxiety disorders did not differ by IED. Severe functional impairment associated with anxiety was higher among adolescents (39.3%) and adults (45.7%) with IED than those without IED (29.2 and 28.2%, respectively). Comorbidity for all other disorders was elevated. However, individuals with anxiety disorders and IED were no more likely to use treatment services than those with anxiety disorders without IED., Conclusions: Individuals with IED concomitant to anxiety disorder, especially social phobia and panic, are at marked risk for worse functional impairment and a higher burden of comorbidity, but onset and course of anxiety disorder do not differ, and those with anxiety and IED are no more likely to utilize treatment services. Assessment, identification, and specialized treatment of anger in the context of anxiety disorders are critical to reducing burden., (© 2015 Wiley Periodicals, Inc.)

Background: Intergenerational effects of child abuse have been documented, but it is unknown whether maternal childhood abuse influences offspring mental health in adolescence or adulthood., Methods: To examine whether maternal experience of childhood abuse is associated with depressive symptoms in adolescent and young adult offspring, we linked data from two large longitudinal cohorts of women (N = 8,882) and their offspring (N = 11,402), and we examined three possible pathways by which maternal experience of abuse might be associated with offspring depressive symptoms: maternal mental health, family characteristics, and offspring's own experience of abuse., Results: Offspring of women who experienced severe versus no childhood abuse had greater likelihood of high depressive symptoms (RR = 1.78, 95% CI = 1.47, 2.16) and persistent high depressive symptoms (RR = 2.47, 95% CI = 1.37, 4.44). Maternal mental health accounted for 20.9% and offspring's exposure to abuse accounted for 30.3% of the elevated risk of high depressive symptoms. Disparities in offspring depressive symptoms by maternal abuse exposure were evident at age 12 years and persisted through age 31 years., Conclusions: Findings provide evidence that childhood abuse adversely affects the mental health of the victim's offspring well into adulthood. As offspring exposure to abuse and maternal mental health accounted for more than 50% of the elevated risk of high depressive symptoms among offspring of women who experienced abuse, improving maternal mental health and parenting practices may reduce offspring risk for depressive symptoms in these families., (© 2015 Wiley Periodicals, Inc.)

Objective: Individuals with posttraumatic stress disorder (PTSD) exhibit heightened amygdala reactivity and atypical activation patterns in the medial prefrontal cortex (mPFC) in response to negative emotional information. It is unknown whether these aspects of neural function are risk factors for PTSD or consequences of either trauma exposure or onset of the disorder. We had a unique opportunity to investigate this issue following the terrorist attacks at the 2013 Boston Marathon and the ensuing manhunt and shelter in place order. We examined associations of neural function measured prior to the attack with PTSD symptom onset related to these events., Methods: A sample of 15 adolescents (mean age = 16.5 years) who previously participated in a neuroimaging study completed a survey assessing posttraumatic symptoms related to the terrorist attack. We examined blood oxygen level dependent (BOLD) response to viewing and actively down-regulating emotional responses to negative stimuli in regions previously associated with PTSD, including the amygdala, hippocampus, and mPFC, as prospective predictors of posttraumatic symptom onset., Results: Increased BOLD signal to negative emotional stimuli in the left amygdala was strongly associated with posttraumatic symptoms following the attack. Reduced bilateral hippocampal activation during effortful attempts to down-regulate emotional responses to negative stimuli was also associated with greater posttraumatic symptoms. Associations of amygdala reactivity with posttraumatic symptoms were robust to controls for pre-existing depression, anxiety, and PTSD symptoms and prior exposure to violence., Conclusions: Amygdala reactivity to negative emotional information might represent a neurobiological marker of vulnerability to traumatic stress and, potentially, a risk factor for PTSD., (© 2014 Wiley Periodicals, Inc.)

Background: Terrorist attacks have been shown to precipitate posttraumatic stress disorder (PTSD) symptomatology in children and adolescents, particularly among youths with high exposure to media coverage surrounding such events. Media exposure may be particularly likely to trigger PTSD symptoms in youths with high physiological reactivity to stress or with prior psychopathology or exposure to violence. We examined the interplay between media exposure, preattack psychopathology, autonomic nervous system (ANS) reactivity, and prior violence exposure in predicting PTSD symptom onset following the terrorist attack at the 2013 Boston Marathon., Methods: A community sample of 78 adolescents (mean age = 16.7 years, 65% female) completed a survey about the bombings, including media exposure to the event and PTSD symptoms. All respondents participated in a study assessing psychopathology prior to the attack, and sympathetic and parasympathetic reactivity to a laboratory-based stressor was assessed in a subset (N = 44) of this sample. We examined the associations of media exposure, ANS reactivity, preattack psychopathology, and prior violence exposure with onset of PTSD symptoms related to the bombings., Results: Media exposure, preattack psychopathology, and prior violence exposure were associated with PTSD symptoms. Moreover, media exposure interacted with sympathetic reactivity to predict PTSD symptom onset, such that adolescents with lower levels of sympathetic reactivity developed PTSD symptoms only following high exposure to media coverage of the attack., Conclusions: We provide novel evidence that physiological reactivity prior to exposure to an unpredictable traumatic stressor predicts PTSD symptom onset. These findings have implications for identifying youths most vulnerable to PTSD following wide-scale trauma., (© 2014 Wiley Periodicals, Inc.)

Background: The development of the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) and ICD-11 has led to reconsideration of diagnostic criteria for posttraumatic stress disorder (PTSD). The World Mental Health (WMH) Surveys allow investigation of the implications of the changing criteria compared to DSM-IV and ICD-10., Methods: WMH Surveys in 13 countries asked respondents to enumerate all their lifetime traumatic events (TEs) and randomly selected one TE per respondent for PTSD assessment. DSM-IV and ICD-10 PTSD were assessed for the 23,936 respondents who reported lifetime TEs in these surveys with the fully structured Composite International Diagnostic Interview (CIDI). DSM-5 and proposed ICD-11 criteria were approximated. Associations of the different criteria sets with indicators of clinical severity (distress-impairment, suicidality, comorbid fear-distress disorders, PTSD symptom duration) were examined to investigate the implications of using the different systems., Results: A total of 5.6% of respondents met criteria for "broadly defined" PTSD (i.e., full criteria in at least one diagnostic system), with prevalence ranging from 3.0% with DSM-5 to 4.4% with ICD-10. Only one-third of broadly defined cases met criteria in all four systems and another one third in only one system (narrowly defined cases). Between-system differences in indicators of clinical severity suggest that ICD-10 criteria are least strict and DSM-IV criteria most strict. The more striking result, though, is that significantly elevated indicators of clinical significance were found even for narrowly defined cases for each of the four diagnostic systems., Conclusions: These results argue for a broad definition of PTSD defined by any one of the different systems to capture all clinically significant cases of PTSD in future studies., (© 2014 Wiley Periodicals, Inc.)

Background: Clinical research suggests that posttraumatic stress disorder (PTSD) patients exposed to multiple traumatic events (TEs) rather than a single TE have increased morbidity and dysfunction. Although epidemiological surveys in the United States and Europe also document high rates of multiple TE exposure, no population-based cross-national data have examined this issue., Methods: Data were analyzed from 20 population surveys in the World Health Organization World Mental Health Survey Initiative (n = 51,295 aged 18+). The Composite International Diagnostic Interview (3.0) assessed 12-month PTSD and other common DSM-IV disorders. Respondents with 12-month PTSD were assessed for single versus multiple TEs implicated in their symptoms. Associations were examined with age of onset (AOO), functional impairment, comorbidity, and PTSD symptom counts., Results: 19.8% of respondents with 12-month PTSD reported that their symptoms were associated with multiple TEs. Cases who associated their PTSD with four or more TEs had greater functional impairment, an earlier AOO, longer duration, higher comorbidity with mood and anxiety disorders, elevated hyperarousal symptoms, higher proportional exposures to partner physical abuse and other types of physical assault, and lower proportional exposure to unexpected death of a loved one than cases with fewer associated TEs., Conclusions: A risk threshold was observed in this large-scale cross-national database wherein cases who associated their PTSD with four or more TEs presented a more "complex" clinical picture with substantially greater functional impairment and greater morbidity than other cases of PTSD. PTSD cases associated with four or more TEs may merit specific and targeted intervention strategies., (© 2013 Wiley Periodicals, Inc.)

Background: Child maltreatment is a potent risk factor for psychopathology. Although the developmental timing of first exposure to maltreatment is considered important in shaping risk of future psychopathology, no consensus exists on whether earlier or later exposures are more deleterious. This study examines whether age at first exposure to abuse is associated with subsequent depression and suicidal ideation., Methods: Data were drawn from the National Longitudinal Study of Adolescent Health (n = 15,701). Timing of first maltreatment exposure was classified using: (1) a crude measure capturing early childhood (ages 0-5), middle childhood (ages 6-10), or adolescence (ages 11-17); and (2) a refined measure capturing infancy (ages 0-2), preschool (ages 3-5), latency (ages 6-8), prepubertal (ages 9-10), pubertal (ages 11-13), or adolescence (ages 14-17). We examined whether timing of first exposure was associated with depression and suicidal ideation in early adulthood in the entire sample and among those exposed to maltreatment., Results: Respondents exposed to abuse, particularly physical abuse, at any age had a higher odds of depression and suicidal ideation in young adulthood than non-maltreated respondents. Among maltreated respondents, exposure during early childhood (ages 0-5), particularly preschool (ages 3-5), was most strongly associated with depression. Respondents first exposed to physical abuse during preschool had a 77% increase in the odds of depression and those first exposed to sexual abuse during early childhood had a 146% increase in the odds of suicidal ideation compared to respondents maltreated as adolescents., Conclusions: Developmental timing of first exposure to maltreatment influences risk for depression and suicidal ideation. Whether these findings are evidence for biologically based sensitive periods requires further study., (© 2013 Wiley Periodicals, Inc.)

Background: Potentially traumatic events (PTEs) are common in the population, yet, the impact of total burden and specific types of PTEs on physical health has not been systematically investigated., Methods: Data were drawn from the Detroit Neighborhood Health Study, a community sample of predominately African Americans living in Detroit, Michigan, interviewed in 2008-2009 (N = 1,547) and in 2009-2010 (N = 1,054). Kaplan-Meier and Cox proportional hazards models were used., Results: Respondents with the highest levels of PTE exposure (8+ events) had an average age of adverse physical health condition diagnosis that was 15 years earlier than respondents with no exposure. There was a monotonic relation between number of PTEs and arthritis risk. Compared to those who reported no lifetime events, respondents with 1-2, 3-4, 5-7, and 8+ traumatic events had 1.06, 1.12, 1.73, and 2.44 times the hazard of arthritis. Assaultive violence (HR = 1.7; 95% CI 1.2-2.3) and other threats to physical integrity (HR = 1.5, 95% CI 1.1-2.1) were particularly strong risk factors for arthritis., Conclusions: These results provide novel evidence linking PTEs, particularly those involving violence and threat to life, to elevated risk for arthritic conditions. Efforts to prevent or mitigate traumatic event exposures may have a broad range of benefits for health., (© 2013 Wiley Periodicals, Inc.)

Background: Although irritability is a core symptom of DSM-IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression-equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross-national community-based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729)., Methods: The assessment of MDD in the WHO Composite International Diagnostic Interview includes one question about persistent irritability. We examined two expansions of the definition of MDD involving this question: (1) cases with dysphoria and/or anhedonia and exactly four of nine Criterion A symptoms plus irritability; and (2) cases with two or more weeks of irritability plus four or more other Criterion A MDD symptoms in the absence of dysphoria or anhedonia., Results: Adding irritability as a tenth Criterion A symptom increased lifetime prevalence by 0.4% (from 11.2 to 11.6%). Adding episodes of persistent irritability increased prevalence by an additional 0.2%. Proportional prevalence increases were significantly higher, but nonetheless small, among males compared to females. Rates of severe role impairment were significantly lower among respondents with this irritable depression who did not meet conventional DSM-IV criteria than those with DSM-IV MDD., Conclusion: Although limited by the superficial assessment in this single question on irritability, results do not support expanding adult MDD criteria to include irritable mood., (© 2013 Wiley Periodicals, Inc.)

Background: A growing literature indicates that genetic variation, in combination with adverse early life experiences, shapes risk for later mental illness. Recent work also suggests that molecular variation at the ADCYAP1R1 locus is associated with posttraumatic stress disorder (PTSD) in women. We sought to test whether childhood maltreatment (CM) interacts with ADCYAP1R1 genotype to predict PTSD in women., Methods: Data were obtained from 495 adult female participants from the Detroit Neighborhood Health Study. Genotyping of rs2267735, an ADCYAP1R1 variant, was conducted via TaqMan assay. PTSD, depression, and CM exposure were assessed via structured interviews. Main and interacting effects of ADCYAP1R1 and CM levels on past month PTSD and posttraumatic stress (PTS) severity were examined using logistic regression and a general linear model, respectively. As a secondary analysis, we also assessed main and interacting effects of ADCYAP1R1 and CM variation on risk of past-month depression diagnosis and symptom severity., Results: No significant main effects were observed for ADCYAP1R1 genotype on either PTSD/PTS severity. In contrast, a significant ADCYAP1R1 × CM interaction was observed for both past month PTSD and PTS severity, with carriers of the "C" allele showing enhanced risk for these outcomes among women exposed to CM. No significant main or interaction effects were observed for past month depression/depression severity., Conclusions: Genetic variation at the ADCYAP1R1 locus interacts with CM to shape risk of later PTSD, but not depression, among women. The molecular mechanisms contributing to this interaction require further investigation., (© 2012 Wiley Periodicals, Inc.)

Background: Although losses are important consequences of disasters, few epidemiological studies of disasters have assessed complicated grief (CG) and none assessed CG associated with losses other than death of loved one., Methods: Data come from the baseline survey of the Hurricane Katrina Community Advisory Group, a representative sample of 3,088 residents of the areas directly affected by Hurricane Katrina. A brief screen for CG was included containing four items consistent with the proposed DSM-V criteria for a diagnosis of bereavement-related adjustment disorder., Results: Fifty-eight and half percent of respondents reported a significant hurricane-related loss: Most-severe losses were 29.0% tangible, 9.5% interpersonal, 8.1% intangible, 4.2% work/financial, and 3.7% death of loved one. Twenty-six point one percent respondents with significant loss had possible CG and 7.0% moderate-to-severe CG. Death of loved one was associated with the highest conditional probability of moderate-to-severe CG (18.5%, compared to 1.1-10.5% conditional probabilities for other losses), but accounted for only 16.5% of moderate-to-severe CG due to its comparatively low prevalence. Most moderate-to-severe CG was due to tangible (52.9%) or interpersonal (24.0%) losses. Significant predictors of CG were mostly unique to either bereavement (racial-ethnic minority status, social support) or other losses (prehurricane history of psychopathology, social competence.)., Conclusions: Nonbereavement losses accounted for the vast majority of hurricane-related possible CG despite risk of CG being much higher in response to bereavement than to other losses. This result argues for expansion of research on CG beyond bereavement and alerts clinicians to the need to address postdisaster grief associated with a wide range of losses., (© 2011 Wiley-Liss, Inc.)

Background: We examined patterns and correlates of speed of recovery of estimated posttraumatic stress disorder (PTSD) among people who developed PTSD in the wake of Hurricane Katrina., Method: A probability sample of prehurricane residents of areas affected by Hurricane Katrina was administered a telephone survey 7-19 months following the hurricane and again 24-27 months posthurricane. The baseline survey assessed PTSD using a validated screening scale and assessed a number of hypothesized predictors of PTSD recovery that included sociodemographics, prehurricane history of psychopathology, hurricane-related stressors, social support, and social competence. Exposure to posthurricane stressors and course of estimated PTSD were assessed in a follow-up interview., Results: An estimated 17.1% of respondents had a history of estimated hurricane-related PTSD at baseline and 29.2% by the follow-up survey. Of the respondents who developed estimated hurricane-related PTSD, 39.0% recovered by the time of the follow-up survey with a mean duration of 16.5 months. Predictors of slow recovery included exposure to a life-threatening situation, hurricane-related housing adversity, and high income. Other sociodemographics, history of psychopathology, social support, social competence, and posthurricane stressors were unrelated to recovery from estimated PTSD., Conclusions: The majority of adults who developed estimated PTSD after Hurricane Katrina did not recover within 18-27 months. Delayed onset was common. Findings document the importance of initial trauma exposure severity in predicting course of illness and suggest that pre- and posttrauma factors typically associated with course of estimated PTSD did not influence recovery following Hurricane Katrina., (© 2011 Wiley-Liss, Inc.)

Background: Although numerous studies have examined the role of latent predispositions to internalizing and externalizing disorders in the structure of comorbidity among common mental disorders, none examined latent predispositions in predicting development of comorbidity., Methods: A novel method was used to study the role of latent variables in the development of comorbidity among lifetime DSM-IV disorders in the National Comorbidity Surveys. Broad preliminary findings are briefly presented to describe the method. The method used survival analysis to estimate time-lagged associations among 18 lifetime DSM-IV anxiety, mood, behavior, and substance disorders. A novel estimation approach examined the extent to which these predictive associations could be explained by latent canonical variables representing internalizing and externalizing disorders., Results: Consistently significant positive associations were found between temporally primary and secondary disorders. Within-domain time-lagged associations were generally stronger than between-domain associations. The vast majority of associations were explained by a model that assumed mediating effects of latent internalizing and externalizing variables, although the complexity of this model differed across samples. A number of intriguing residual associations emerged that warrant further investigation., Conclusions: The good fit of the canonical model suggests that common causal pathways account for most comorbidity among the disorders considered. These common pathways should be the focus of future research on the development of comorbidity. However, the existence of several important residual associations shows that more is involved than simple mediation. The method developed to carry out these analyses provides a unique way to pinpoint these significant residual associations for subsequent focused study., (Depression and Anxiety, 2011. © 2011 Wiley-Liss, Inc.)

Background: Adverse child environments are associated with the onset of mood and anxiety disorders in adulthood. The mechanisms underlying these life-course associations remain poorly understood. We investigate whether emotional reactivity to stress is a mechanism in the association between childhood environment characteristics and adult mood and anxiety disorders., Methods: Data are from the Study of Adult Development, a longitudinal study of men (N = 268) followed for nearly seven decades beginning in late adolescence. Childhood social environment characteristics were assessed during home visits and interviews with respondents' parents at entry into the study. Stress reactivity was assessed during respondents' sophomore year of college via physician exam. Onset of mood and anxiety disorders in adulthood was ascertained by research psychiatrists who completed chart reviews of interview, questionnaire, and physical exam data collected during repeated assessments from age 20 to 70., Results: Respondents with better overall childhood environments and a greater number of environmental strengths were at lower odds of developing a mood or anxiety disorder in adulthood than respondents with more adverse childhood environments. Higher stress reactivity was observed among respondents from families with lower socio-economic status and with childhood environments characterized by greater conflict and adversity. Elevated stress reactivity, in turn, predicted the onset of adult mood and anxiety disorders., Conclusion: Heightened emotional reactivity in early adulthood is associated with both adverse childhood environments and elevated risk for developing mood and anxiety disorders in adulthood. Emotional reactivity may be one mechanism linking childhood adversity to mood and anxiety disorders in adulthood., (© 2010 Wiley-Liss, Inc.)