# Publications

2014
Sheridan, M. A., & McLaughlin, K. A. (2014). Dimensions of early experience and neural development: deprivation and threat. Trends in Cognitive Sciences , 18 (11), 580–585.Abstract
Over the past decade, a growing area of research has focused on adverse childhood experiences (ACEs) and their impacts on neural and developmental outcomes. Work in the field to-date has generally conceptualized ACEs in terms of exposure to stress while overlooking the underlying dimensions of environmental experience that may distinctly impact neural development. Here, we propose a novel framework that differentiates between deprivation (absence of expected cognitive and social input) and threat (presence of a threat to one's physical integrity). We draw support for the neural basis of this distinction from studies on fear learning and sensory deprivation in animals to highlight potential mechanisms through which experiences of threat and deprivation could affect neural structure and function in humans.
Stein, D. J., McLaughlin, K. A., Koenen, K. C., Atwoli, L., Friedman, M. J., Hill, E. D., Maercker, A., et al. (2014). DSM-5 and ICD-11 definitions of posttraumatic stress disorder: investigating "narrow" and "broad" approaches. Depression and Anxiety , 31 (6), 494–505.Abstract
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.
Kessler, R. C., Rose, S., Koenen, K. C., Karam, E. G., Stang, P. E., Stein, D. J., Heeringa, S. G., et al. (2014). How well can post-traumatic stress disorder be predicted from pre-trauma risk factors? An exploratory study in the WHO World Mental Health Surveys. World psychiatry: official journal of the World Psychiatric Association (WPA) , 13 (3), 265–274.Abstract
Post-traumatic stress disorder (PTSD) should be one of the most preventable mental disorders, since many people exposed to traumatic experiences (TEs) could be targeted in first response settings in the immediate aftermath of exposure for preventive intervention. However, these interventions are costly and the proportion of TE-exposed people who develop PTSD is small. To be cost-effective, risk prediction rules are needed to target high-risk people in the immediate aftermath of a TE. Although a number of studies have been carried out to examine prospective predictors of PTSD among people recently exposed to TEs, most were either small or focused on a narrow sample, making it unclear how well PTSD can be predicted in the total population of people exposed to TEs. The current report investigates this issue in a large sample based on the World Health Organization (WHO)'s World Mental Health Surveys. Retrospective reports were obtained on the predictors of PTSD associated with 47,466 TE exposures in representative community surveys carried out in 24 countries. Machine learning methods (random forests, penalized regression, super learner) were used to develop a model predicting PTSD from information about TE type, socio-demographics, and prior histories of cumulative TE exposure and DSM-IV disorders. DSM-IV PTSD prevalence was 4.0% across the 47,466 TE exposures. 95.6% of these PTSD cases were associated with the 10.0% of exposures (i.e., 4,747) classified by machine learning algorithm as having highest predicted PTSD risk. The 47,466 exposures were divided into 20 ventiles (20 groups of equal size) ranked by predicted PTSD risk. PTSD occurred after 56.3% of the TEs in the highest-risk ventile, 20.0% of the TEs in the second highest ventile, and 0.0-1.3% of the TEs in the 18 remaining ventiles. These patterns of differential risk were quite stable across demographic-geographic sub-samples. These results demonstrate that a sensitive risk algorithm can be created using data collected in the immediate aftermath of TE exposure to target people at highest risk of PTSD. However, validation of the algorithm is needed in prospective samples, and additional work is warranted to refine the algorithm both in terms of determining a minimum required predictor set and developing a practical administration and scoring protocol that can be used in routine clinical practice.
Slopen, N., McLaughlin, K. A., & Shonkoff, J. P. (2014). Interventions to improve cortisol regulation in children: a systematic review. Pediatrics , 133 (2), 312–326.Abstract
Childhood adversity is associated with physiologic dysregulation across multiple biological systems; however, relatively little is known about whether these changes are reversible with intervention. The objective of this review was to examine evidence for the effectiveness of interventions to promote healthy cortisol regulation in children. We selected articles from English-language publications in PubMed and EBSCO databases through 2012. Two independent reviewers assessed articles against eligibility criteria. Eligible studies were randomized controlled or quasi-experimental studies designed to improve relationships, environments, or psychosocial functioning in children and examined cortisol as an outcome. We identified 19 articles. There was substantial heterogeneity across studies with regard to age, selection criteria, intervention design, cortisol assessment, and follow-up duration. Eighteen of the 19 articles reported at least 1 difference in baseline cortisol, diurnal cortisol, or cortisol responsivity between intervention and control participants. Importantly, however, there was remarkable inconsistency with regard to how the interventions influenced cortisol. Therefore, studies that included a low-risk comparison group (n = 8) provided critical insight, and each found some evidence that postintervention cortisol levels in the intervention group approximated the low-risk comparison group and differed from children receiving usual care. In conclusion, existing studies show that cortisol activity can be altered by psychosocial interventions. These findings are promising, not only because they indicate physiologic plasticity that can be leveraged by interventions but also because they suggest it may be possible to repair regulatory systems after childhood adversity, which could inform strategies for reducing health disparities and promoting lasting improvements in health.
Busso, D. S., McLaughlin, K. A., & Sheridan, M. A. (2014). Media exposure and sympathetic nervous system reactivity predict PTSD symptoms after the Boston marathon bombings. Depression and Anxiety , 31 (7), 551–558.Abstract
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.
Aldao, A., McLaughlin, K. A., Hatzenbuehler, M. L., & Sheridan, M. A. (2014). The Relationship between Rumination and Affective, Cognitive, and Physiological Responses to Stress in Adolescents. Journal of Experimental Psychopathology , 5 (3), 272–288.Abstract
Although previous studies have established that rumination influences responses to stressful life events, the mechanisms underlying this relationship remain inadequately understood. The current study examines the relationship between trait rumination and affective, cognitive, and physiological responses to a standardized laboratory-based stressor in adolescents. A community-based sample of adolescents (N = 157) aged 13-17 completed the Trier Social Stress Test (TSST). Affective, cognitive, and physiological responses were obtained before, during, and after the TSST. Adolescents who engaged in habitual rumination experienced greater negative affect and more negative cognitive appraisals in response to the TSST than adolescents with lower levels of rumination. Rumination was unrelated to heart rate reactivity, but predicted slower heart rate recovery from the TSST, indicating that rumination might be specifically associated with physiological recovery from stress. Rumination is associated with negative affective, cognitive, and physiological responses following stressors, suggesting potential mechanisms through which it might increase risk for psychopathology.
McLaughlin, K. A., Aldao, A., Wisco, B. E., & Hilt, L. M. (2014). Rumination as a transdiagnostic factor underlying transitions between internalizing symptoms and aggressive behavior in early adolescents. Journal of Abnormal Psychology , 123 (1), 13–23.Abstract
The high degree of comorbidity among mental disorders has generated interest in identifying transdiagnostic processes associated with multiple types of psychopathology. Susan Nolen-Hoeksema conceptualized rumination as one such transdiagnostic process associated with depression, anxiety, substance abuse, binge eating, and self-injurious behavior. The degree to which rumination accounts for the co-occurrence of internalizing and externalizing psychopathology, however, has never been tested. We used a sample of early adolescents (N = 1,065) assessed at 3 time points spanning 7 months to examine (a) the reciprocal prospective associations between rumination and aggressive behavior in adolescents, (b) whether rumination explained the longitudinal associations of aggressive behavior with depression and anxiety symptoms, and (c) gender differences in these associations. Rumination predicted increases over time in aggressive behavior, and aggression was associated with increases in rumination over time only for boys. Rumination fully mediated the longitudinal association of aggression with subsequent anxiety symptoms and of both depression and anxiety symptoms with subsequent aggression in boys but not girls. Rumination did not explain the association between aggression and subsequent depressive symptoms for either boys or girls. These findings provide novel evidence for the role of rumination as a transdiagnostic factor underlying transitions between internalizing and externalizing symptoms among males during early adolescence. Interventions aimed at reducing rumination may have beneficial influences on multiple forms of psychopathology and on the development of comorbidity. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
Everett, B. G., Rosario, M., McLaughlin, K. A., & Austin, S. B. (2014). Sexual orientation and gender differences in markers of inflammation and immune functioning. Annals of Behavioral Medicine: A Publication of the Society of Behavioral Medicine , 47 (1), 57–70.Abstract
BACKGROUND: Sexual minorities have documented elevated risk factors that can lead to inflammation and poor immune functioning. PURPOSE: This study aims to investigate disparities in C-reactive protein (CRP) and Epstein-Barr virus (EBV) by gender and sexual orientation. METHODS: We used the National Longitudinal Study of Adolescent Health to examine disparities in CRP (N = 11,462) and EBV (N = 11,812). RESULTS: Among heterosexuals, women had higher levels of CRP and EBV than men. However, sexual minority men had higher levels of CRP and EBV than heterosexual men and sexual minority women. Lesbians had lower levels of CRP than heterosexual women. CONCLUSIONS: Gender differences in CRP and EBV found between men and women who identify as 100 % heterosexual were reversed among sexual minorities and not explained by known risk factors (e.g., victimization, alcohol and tobacco use, and body mass index). More nuanced approaches to addressing gender differences in sexual orientation health disparities that include measures of gender nonconformity and minority stress are needed.
Hatzenbuehler, M. L., Slopen, N., McLaughlin, K. A., & McLaughlin, K. A. (2014). Stressful life events, sexual orientation, and cardiometabolic risk among young adults in the United States. Health Psychology: Official Journal of the Division of Health Psychology, American Psychological Association , 33 (10), 1185–1194.Abstract
{OBJECTIVE: The goal of the present study was to examine whether sexual minority young adults are more vulnerable to developing cardiometabolic risk following exposure to stressful life events than heterosexual young adults. METHOD: Data came from the National Longitudinal Study for Adolescent Health (Shin, Edwards, & Heeren, 2009; Brummett et al., 2013), a prospective nationally representative study of U.S. adolescents followed into young adulthood. A total of 306 lesbian, gay, and bisexual (LGB) respondents and 6,667 heterosexual respondents met inclusion criteria for this analysis. Measures of cumulative stressful life events were drawn from all 4 waves of data collection; sexual orientation and cardiometabolic biomarkers were assessed at Wave 4 (2008-2009). RESULTS: Gay/bisexual men exposed to 1-2 ($\beta$ = 0.71
Hatzenbuehler, M. L., & McLaughlin, K. A. (2014). Structural stigma and hypothalamic-pituitary-adrenocortical axis reactivity in lesbian, gay, and bisexual young adults. Annals of Behavioral Medicine: A Publication of the Society of Behavioral Medicine , 47 (1), 39–47.Abstract
BACKGROUND: Youth exposed to extreme adverse life conditions have blunted cortisol responses to stress. PURPOSE: This study aims to examine whether growing up in highly stigmatizing environments similarly shapes stigmatized individuals' physiological responses to identity-related stress. METHODS: We recruited 74 lesbian, gay, and bisexual young adults (mean age = 23.68) from 24 states with varying levels of structural stigma surrounding homosexuality. State-level structural stigma was coded based on several dimensions, including policies that exclude sexual minorities from social institutions (e.g., same-sex marriage). Participants were exposed to a laboratory stressor, the Trier Social Stress Test (TSST), and neuroendocrine measures were collected. RESULTS: Lesbian, gay, and bisexual young adults who were raised in highly stigmatizing environments as adolescents evidenced a blunted cortisol response following the TSST compared to those from low-stigma environments. CONCLUSIONS: The stress of growing up in environments that target gays and lesbians for social exclusion may exert biological effects that are similar to traumatic life experiences.
McLaughlin, K. A., Alves, S., & Sheridan, M. A. (2014). Vagal regulation and internalizing psychopathology among adolescents exposed to childhood adversity. Developmental Psychobiology , 56 (5), 1036–1051.Abstract
Childhood adversity (CA) is strongly associated with youth psychopathology. Identifying factors that reduce vulnerability following CA is critical for developing preventive interventions. Vagal tone and vagal reactivity following psychosocial stressors might influence psychopathology among youths exposed to CA. We acquired heart period and impedance cardiography data to calculate respiratory sinus arrhythmia (RSA) and preejection period (PEP) from 157 adolescents aged 13-17 years at rest and during the Trier Social Stress Test (TSST). Internalizing and externalizing symptoms and multiple forms of CA were assessed. Resting RSA and RSA reactivity interacted with CA in predicting internalizing but not externalizing psychopathology; CA was unassociated with internalizing problems in adolescents with high resting RSA and RSA reactivity. No interactions were observed with PEP. High resting RSA predicted greater vagal rebound and accelerated heart rate recovery following the TSST, highlighting one potential mechanism underlying low internalizing symptoms following CA among youths with high vagal tone.
McLaughlin, K. A., Sheridan, M. A., Winter, W., Fox, N. A., Zeanah, C. H., & Nelson, C. A. (2014). Widespread reductions in cortical thickness following severe early-life deprivation: a neurodevelopmental pathway to attention-deficit/hyperactivity disorder. Biological Psychiatry , 76 (8), 629–638.Abstract
BACKGROUND: Children exposed to early-life psychosocial deprivation associated with institutional rearing are at markedly elevated risk of developing attention-deficit/hyperactivity disorder (ADHD). Neurodevelopmental mechanisms that explain the high prevalence of ADHD in children exposed to institutionalization are unknown. We examined whether abnormalities in cortical thickness and subcortical volume were mechanisms explaining elevations in ADHD among children raised in institutional settings. METHODS: Data were drawn from the Bucharest Early Intervention Project, a cohort of children raised from early infancy in institutions in Romania (n = 58) and age-matched community control subjects (n = 22). Magnetic resonance imaging data were acquired when children were aged 8 to 10 years, and ADHD symptoms were assessed using the Health and Behavior Questionnaire. RESULTS: Children reared in institutions exhibited widespread reductions in cortical thickness across prefrontal, parietal, and temporal regions relative to community control subjects. No group differences were found in the volume of subcortical structures. Reduced thickness across numerous cortical areas was associated with higher levels of ADHD symptoms. Cortical thickness in lateral orbitofrontal cortex, insula, inferior parietal cortex, precuneus, superior temporal cortex, and lingual gyrus mediated the association of institutionalization with inattention and impulsivity; additionally, supramarginal gyrus thickness mediated the association with inattention and fusiform gyrus thickness mediated the association with impulsivity. CONCLUSIONS: Severe early-life deprivation disrupts cortical development resulting in reduced thickness in regions with atypical function during attention tasks in children with ADHD, including the inferior parietal cortex, precuneus, and superior temporal cortex. These reductions in thickness are a neurodevelopmental mechanism explaining elevated ADHD symptoms in children exposed to institutional rearing.
2013
Mclaughlin, K., Sheridan, M., & Nelson, C. (2013). Adverse Childhood Experiences and Brain Development: Neurobiological Mechanisms linking the Social Environment to Psychiatric Disorders. In K. Koenen, S. Rudenstine, E. Susser, & S. Galea (Ed.), A Life Course Approach to Mental Disorders (pp. 249-258) . Oxford University Press.
Mclaughlin, K. (2013). The developmental psychopathology of major depression. In M. Power (Ed.), Mood Disorders: A Handbook of Science and Practice (2nd ed. pp. 107-141) . Wiley-Blackwell.
Slopen, N., & Mclaughlin, K. (2013). Exposure to intimate partner violence and parental depression increases risk of ADHD in preschool children. Evidence-based mental health , 16 (4), 102. Publisher's VersionAbstract
QUESTION Question: Does exposure to parental depression or intimate partner violence (IPV) during the first 3 years of life have an effect on a child's subsequent mental health?, People: A total of 2422 children (52% boys, Hispanic/ Latino 45.5%, Black 40.6%, White 10.5%) visiting health centres served by the Child Health Improvement through Computer Automation (CHICA) paediatric primary care system, from birth to age 3 years, and again when aged between 37 and 72 months., Setting: Four community health centres, Indianapolis, Indiana, USA; November 2004–June 2012., Risk factors: Exposure to IPV and parental depression within the first 3 years of life. This information was collected using screening questions presented in a prescreener form which parents completed in the clinic waiting rooms. To screen for depression, The Patient Health Questionnaire (PHQ-2) was used until 2010, and then replaced by the anxiety subscale of the Edinburgh Postnatal Depression Scale (EPDS-3). IPV was screened using the questions ‘Has your partner kicked, hit or slapped you?’ and ‘Do you feel safe in your home?’, Outcomes: Child mental health diagnosis or psychotropic drug treatment received between the ages of 3 and 3. Diagnoses were identified using International Classification of Diseases-9 codes for attention deficit hyperactivity disorder (ADHD), disruptive behaviour disorder, depression, anxiety, sleep disturbance or adjustment disorder. Prescription information was taken from the Indiana Network for Patient Care and Regenstriel Medical Record Systems databases. METHODS Design: Prospective cohort study., Follow-up period: Three years. MAIN RESULTS Within the first 3 years of the child's life, 1591 (65.7%) of parents reported neither IPV nor depression, 704 (29.1%) reported depression only, 69 (2.8%) reported IPV only and 58 (2.4%) reported IPV as well as depression. Between ages 3 and 6 years, 48 (2%) of children had received psychotropic medication, 80 children (3.3%) were diagnosed with ADHD, 209 (8.7%) with disruptive behaviour disorder, 9 (0.4%) with depression, 17 (0.7%) with anxiety, 7 (0.3%) with sleep disturbance and 41 (1.7%) with adjustment disorder. Prevalence of ADHD was higher in children exposed to parental depression compared with those not exposed (4.5% vs 2.8%, p<=0.03). Psychotropic drug prescriptions were higher in children exposed to parental depression compared with those who were not exposed (2.9% vs 1.6%, p<=0.03). Multivariate regression analysis revealed that increased exposure to IPV as well as depression was associated with increased risk of ADHD diagnosis compared with non-exposure (OR 4.0, 95% CI 1.5 to 10.9; see table). Exposure to parental depression was also associated with increased risk of child psychotropic medication prescription (OR 1.9, 95% CI 1.0 to 3.4). There were no significant associations with exposure to IPV only or with both exposures for any other mental health condition. CONCLUSIONS Exposure to parental IPV and parental depression within the first 3 years of life is associated with increased risk of ADHD diagnosis prior to 6 years. Early exposure to parental depression is associated with increased risk of psychotropic medication prescription.
Slopen, N., McLaughlin, K. A., Dunn, E. C., & Koenen, K. C. (2013). Childhood adversity and cell-mediated immunity in young adulthood: does type and timing matter? Brain, Behavior, and Immunity , 28, 63–71.Abstract
Childhood adversity can have powerful effects on health over the life course. Persistent changes in cell-mediated immune function may be one pathway linking adverse childhood experiences with later disease risk. However, limited research has examined childhood adversity in relation to cell-mediated immune function, and in particular, immune response to latent viruses in adulthood. The present study investigated the association of two types of childhood adversity, socioeconomic disadvantage during adolescence and abuse prior to age 18, with Epstein-Barr Virus (EBV) antibody titers in a large nationally representative sample of young adults aged 24-32years. Data were drawn from the National Longitudinal Study on Adolescent Health, Wave 4 (n=13,162). We examined the associations of three indicators of adolescent SES (parental education, household income, and occupational status) and frequency and timing of physical and sexual abuse with EBV antibodies, controlling for age, sex, race/ethnicity, and presence of a smoker in the household during adolescence. Lower parental occupational status and some categories of lower education were associated with elevated EBV antibodies (p\textless.05), and individuals who reported sexual abuse that occurred more than 10times had elevated EBV antibodies relative to individuals who were not sexually abused (p=0.03). Among individuals exposed to physical abuse, those who were first abused at age 3-5years had heightened EBV antibodies relative to those first abused during adolescence (p=0.004). This study extends prior research linking early adversity and immune function, and provides initial evidence that childhood adversity has a persistent influence on immune responses to latent infection in adulthood.
Slopen, N., Kubzansky, L. D., McLaughlin, K. A., & Koenen, K. C. (2013). Childhood adversity and inflammatory processes in youth: a prospective study. Psychoneuroendocrinology , 38 (2), 188–200.Abstract
BACKGROUND: Retrospective studies show that childhood adversity is associated with systemic inflammation in adulthood. Few prospective studies have examined whether childhood adversity influences inflammation in an observable manner during childhood or adolescence and if these effects are sustained over time. METHODS: Using longitudinal data from the Avon Longitudinal Study of Parents and Children, we examined associations between acute adverse events at seven time points prior to age 8 and inflammation at ages 10 and 15. Inflammatory markers at age 10 included interleukin-6 (IL-6; N=4655) and C-reactive protein (CRP; N=4647), and CRP was measured again at age 15 (N=3286). We further evaluated whether body mass index (BMI), depression, or cigarette smoking mediated associations between adverse events and inflammation. RESULTS: Adverse events in middle childhood (occurring between ages 6 to 8), as well as cumulative adversity from birth to 8 years, were associated with higher levels of IL-6 and CRP at age 10. Adverse events reported in early childhood (1.5years) or middle childhood, and cumulative adversity from birth through 8years predicted increased levels of CRP at age 15, and these associations persisted after adjustment for CRP at age 10. Some, but not all, of these associations were mediated by BMI. CONCLUSIONS: This study documents that exposure to adverse events prior to age 8 is associated with elevated inflammation at age 10 and in mid-adolescence. These findings provide prospective evidence for a biological mechanism by which early experiences may shape long-term health. Future studies with earlier assessments of inflammation are necessary in order to elucidate potential sensitive periods and mechanisms that link childhood adversity to later disease vulnerability.
Stein, D. J., Koenen, K. C., Friedman, M. J., Hill, E., McLaughlin, K. A., Petukhova, M., Ruscio, A. M., et al. (2013). Dissociation in posttraumatic stress disorder: evidence from the world mental health surveys. Biological Psychiatry , 73 (4), 302–312.Abstract
BACKGROUND: Although the proposal for a dissociative subtype of posttraumatic stress disorder (PTSD) in DSM-5 is supported by considerable clinical and neurobiological evidence, this evidence comes mostly from referred samples in Western countries. Cross-national population epidemiologic surveys were analyzed to evaluate generalizability of the subtype in more diverse samples. METHODS: Interviews were administered to 25,018 respondents in 16 countries in the World Health Organization World Mental Health Surveys. The Composite International Diagnostic Interview was used to assess 12-month DSM-IV PTSD and other common DSM-IV disorders. Items from a checklist of past-month nonspecific psychological distress were used to assess dissociative symptoms of depersonalization and derealization. Differences between PTSD with and without these dissociative symptoms were examined across a variety of domains, including index trauma characteristics, prior trauma history, childhood adversity, sociodemographic characteristics, psychiatric comorbidity, functional impairment, and treatment seeking. RESULTS: Dissociative symptoms were present in 14.4% of respondents with 12-month DSM-IV/Composite International Diagnostic Interview PTSD and did not differ between high and low/middle income countries. Symptoms of dissociation in PTSD were associated with high counts of re-experiencing symptoms and net of these symptom counts with male sex, childhood onset of PTSD, high exposure to prior (to the onset of PTSD) traumatic events and childhood adversities, prior histories of separation anxiety disorder and specific phobia, severe role impairment, and suicidality. CONCLUSION: These results provide community epidemiologic data documenting the value of the dissociative subtype in distinguishing a meaningful proportion of severe and impairing cases of PTSD that have distinct correlates across a diverse set of countries.
Uddin, M., Chang, S. - C., Zhang, C., Ressler, K., Mercer, K. B., Galea, S., Keyes, K. M., et al. (2013). Adcyap1r1 genotype, posttraumatic stress disorder, and depression among women exposed to childhood maltreatment. Depression and Anxiety , 30 (3), 251–258.Abstract
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.
Digangi, J., Guffanti, G., McLaughlin, K. A., & Koenen, K. C. (2013). Considering trauma exposure in the context of genetics studies of posttraumatic stress disorder: a systematic review. Biology of Mood & Anxiety Disorders , 3 (1), 2.Abstract
BACKGROUND: Posttraumatic stress disorder (PTSD) is a debilitating anxiety disorder. Surveys of the general population suggest that while 50-85% of Americans will experience a traumatic event in their lifetime, only 2-50% will develop PTSD. Why some individuals develop PTSD following trauma exposure while others remain resilient is a central question in the field of trauma research. For more than half a century, the role of genetic influences on PTSD has been considered as a potential vulnerability factor. However, despite the exponential growth of molecular genetic studies over the past decade, limited progress has been made in identifying true genetic variants for PTSD. METHODS: In an attempt to aid future genome wide association studies (GWAS), this paper presents a systematic review of 28 genetic association studies of PTSD. Inclusion criteria required that 1) all participants were exposed to Criterion A traumatic events, 2) polymorphisms of relevant genes were genotyped and assessed in relation to participants' PTSD status, 3) quantitative methods were used, and 4) articles were published in English and in peer-reviewed journals. In the examination of these 28 studies, particular attention was given to variables related to trauma exposure (e.g. number of traumas, type of trauma). RESULTS: Results indicated that most articles did not report on the GxE interaction in the context of PTSD or present data on the main effects of E despite having data available. Furthermore, some studies that did consider the GxE interaction had significant findings, underscoring the importance of examining how genotypes can modify the effect of trauma on PTSD. Additionally, results indicated that only a small number of genes continue to be studied and that there were marked differences in methodologies across studies, which subsequently limited robust conclusions. CONCLUSIONS: As trauma exposure is a necessary condition for the PTSD diagnosis, this paper identifies gaps in the current literature as well as provides recommendations for how future GWAS studies can most effectively incorporate trauma exposure data in both the design and analysis phases of studies.