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Genomic influences on self-reported childhood maltreatment.

ABSTRACT: Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h²_snp), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltreatment, and (4) quantify genetic overlap of childhood maltreatment with mental and physical health-related phenotypes, and condition the top hits from our analyses when such overlap is present. Genome-wide association analysis for childhood maltreatment was undertaken, using a discovery sample from the UK Biobank (UKBB) (n?=?124,000) and a replication sample from the Psychiatric Genomics Consortium-posttraumatic stress disorder group (PGC-PTSD) (n?=?26,290). h²_snp for childhood maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression. PRS was calculated using PRSice and mtCOJO was used to perform conditional analysis. Two genome-wide significant loci associated with childhood maltreatment (rs142346759, p?=?4.35?×?10^-8, FOXP1; rs10262462, p?=?3.24?×?10^-8, FOXP2) were identified in the discovery dataset but were not replicated in PGC-PTSD. h²_snp for childhood maltreatment was ~6% and the PRS derived from the UKBB was significantly predictive of childhood maltreatment in PGC-PTSD (r²?=?0.0025; p?=?1.8?×?10^-15). The most significant genetic correlation of childhood maltreatment was with depressive symptoms (r_g?=?0.70, p?=?4.65?×?10^-40), although we show evidence that our top hits may be specific to childhood maltreatment. This is the first large-scale genetic study to identify specific variants associated with self-reported childhood maltreatment. Speculatively, FOXP genes might influence externalizing traits and so be relevant to childhood maltreatment. Alternatively, these variants may be associated with a greater likelihood of reporting maltreatment. A clearer understanding of the genetic relationships of childhood maltreatment, including particular abuse subtypes, with a range of phenotypes, may ultimately be useful in in developing targeted treatment and prevention strategies.

SUBMITTER: Dalvie S

PROVIDER: S-EPMC7026037 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Genomic influences on self-reported childhood maltreatment.

Dalvie Shareefa S Maihofer Adam X AX Coleman Jonathan R I JRI Bradley Bekh B Breen Gerome G Brick Leslie A LA Chen Chia-Yen CY Choi Karmel W KW Duncan Laramie E LE Guffanti Guia G Haas Magali M Harnal Supriya S Liberzon Israel I Nugent Nicole R NR Provost Allison C AC Ressler Kerry J KJ Torres Katy K Amstadter Ananda B AB Bryn Austin S S Baker Dewleen G DG Bolger Elizabeth A EA Bryant Richard A RA Calabrese Joseph R JR Delahanty Douglas L DL Farrer Lindsay A LA Feeny Norah C NC Flory Janine D JD Forbes David D Galea Sandro S Gautam Aarti A Gelernter Joel J Hammamieh Rasha R Jett Marti M Junglen Angela G AG Kaufman Milissa L ML Kessler Ronald C RC Khan Alaptagin A Kranzler Henry R HR Lebois Lauren A M LAM Marmar Charles C Mavissakalian Matig R MR McFarlane Alexander A Donnell Meaghan O' MO Orcutt Holly K HK Pietrzak Robert H RH Risbrough Victoria B VB Roberts Andrea L AL Rothbaum Alex O AO Roy-Byrne Peter P Ruggiero Ken K Seligowski Antonia V AV Sheerin Christina M CM Silove Derrick D Smoller Jordan W JW Stein Murray B MB Teicher Martin H MH Ursano Robert J RJ Van Hooff Miranda M Winternitz Sherry S Wolff Jonathan D JD Yehuda Rachel R Zhao Hongyu H Zoellner Lori A LA Stein Dan J DJ Koenen Karestan C KC Nievergelt Caroline M CM

Translational psychiatry 20200127 1

Childhood maltreatment is highly prevalent and serves as a risk factor for mental and physical disorders. Self-reported childhood maltreatment appears heritable, but the specific genetic influences on this phenotype are largely unknown. The aims of this study were to (1) identify genetic variation associated with self-reported childhood maltreatment, (2) estimate SNP-based heritability (h<sup>2</sup><sub>snp</sub>), (3) assess predictive value of polygenic risk scores (PRS) for childhood maltrea ...[more]

PMID: 32066696

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Project description:BackgroundChildhood maltreatment, such as severe emotional, physical, and sexual abuse and neglect, has been linked to impulse control problems and dysfunctional emotional coping. In borderline personality disorder (BPD), a history of childhood maltreatment may worsen difficulties in emotion regulation, which may in turn give rise to impulsive behaviours. The aim of this self-report study was to investigate associations between childhood maltreatment severity, emotion regulation difficulties, and impulsivity in women with BPD compared to healthy and clinical controls.MethodsSixty-one female patients with BPD, 57 clinical controls (CC, women with Attention Deficit Hyperactivity Disorder and/or Substance Use Disorder, without BPD), and 60 female healthy controls (HC) completed self-report scales on childhood trauma (Childhood Trauma Questionnaire, CTQ), difficulties in emotion regulation (Difficulties in Emotion Regulation Scale, DERS), and impulsivity (UPPS Impulsive Behaviour Scale). A conditional process analysis was performed to investigate whether emotion dysregulation statistically mediated the effect of childhood maltreatment severity on impulsivity depending on group (BPD vs. CC vs. HC).ResultsChildhood maltreatment, particularly emotional maltreatment, was positively associated with impulsivity and emotion regulation difficulties across all groups. Difficulties in emotion regulation statistically mediated the effect of childhood maltreatment on impulsivity in BPD, but not in the other groups.ConclusionIn the context of current conceptualizations of BPD and previous research, findings suggest that problems with emotion regulation may be related to a history of childhood maltreatment, which may in turn enhance impulsivity. Targeting emotion dysregulation in psychotherapy and discussing it in relation to childhood maltreatment can help decreasing impulsive behaviors in individuals with BPD. Given the correlational design of our study which does not allow causal conclusions, future studies have to employ prospective, experimental designs and include larger sample sizes to corroborate associations between childhood maltreatment, emotion dysregulation, and impulsivity.

Project description:BackgroundEstimating the prevalence of child maltreatment is challenging due to the absence of a clear 'gold standard' as to what constitutes maltreatment. This systematic review aims to review studies using self-report maltreatment to capture prevalence rates worldwide.MethodsPubMed, Ovid SP and grey literature from the NSPCC, UNICEF, The UK Government, and WHO from 2000 to 2017 were searched. The literature review focused on the variation found in self-reported lifetime prevalence for each type of maltreatment between studies by continent and gender, and how methodological differences may explain differences found.ResultsSexual abuse is the most commonly studied form of maltreatment across the world with median (25th to 75th centile) prevalence of 20.4% (13.2% to 33.6%) and 28.8% (17.0% to 40.2%) in North American and Australian girls respectively, with lower rates generally for boys. Rates of physical abuse were more similar across genders apart from in Europe, which were 12.0% (6.9% to 23.0%) and 27.0% (7.0% to 43.0%) for girls and boys respectively, and often very high in some continents, for example, 50.8% (36.0% to 73.8%) and 60.2% (43.0% to 84.9%) for girls and boys respectively in Africa. Median rates of emotional abuse were nearly double for girls than boys in North America (28.4% vs 13.8% respectively) and Europe (12.9% vs 6.2% respectively) but more similar across genders groups elsewhere. Median rates of neglect were highest in Africa (girls: 41.8%, boys: 39.1%) and South America (girls: 54.8%, boys: 56.7%) but were based on few studies in total, whereas in the two continents with the highest number of studies, median rates differed between girls (40.5%) and boys (16.6%) in North America but were similar in Asia (girls: 26.3%, boys: 23.8%).ConclusionsMedian prevalence rates differ substantially by maltreatment category, gender and by continent. The number of studies and available data also varies and relatively little is known about prevalence for some forms of maltreatment, particularly outside of the North American context. Prevalence rates require caution in interpretation as some variation will reflect methodological differences, including the data collection methods, and how the maltreatment is defined.

Project description:Background:Childhood maltreatment is a strong risk factor for the development of depression in later life. However, the neurobiological mechanisms underlying this vulnerability are not well understood. As depression has been associated with dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and increased responsiveness to psychosocial stressors, we speculated that childhood maltreatment may lead to lasting alteration of the stress response system, thereby increasing the risk of depression. This study investigated the effects of childhood maltreatment on the stress response in healthy subjects while controlling for psychiatric condition. Methods:Forty-eight healthy young adults (24 females) with childhood maltreatment experience and 48 healthy controls (33 females) without such experience were administered the Montreal Imaging Stress Task during functional magnetic resonance imaging. Childhood maltreatment experience was assessed using the 28-item Childhood Trauma Questionnaire (CTQ). Between-group differences in subjective stress levels, whole brain activations and cortisol levels were assessed. Results:Relative to healthy control subjects, individuals exposed to childhood maltreatment exhibited higher subjective stress and cortisol levels. Neurofunctionally, participants with histories of childhood maltreatment displayed significantly increased activation in the dorsolateral prefrontal cortex (dlPFC), insula and precuneus, and decreased activation in ventromedial prefrontal cortex (vmPFC) relative to healthy controls during the psychosocial stress task. Activations in dlPFC and insula correlated with CTQ scores in the childhood maltreatment group. Conclusion:The results of this study show that childhood maltreatment induces lasting changes in brain function and HPA-axis responsiveness to stress. The observed abnormal activation in the dlPFC, insula and vmPFC and enhanced cortisol response are similar to those seen in individuals with depression. This dysfunction might serve as a diathesis that embeds latent vulnerability to psychiatric disorders, and this mechanism provides evidence supporting the stress sensitization model.

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Genomic influences on self-reported childhood maltreatment.

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Genomic influences on self-reported childhood maltreatment.

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