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Andrea Danese - One of the best experts on this subject based on the ideXlab platform.
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Agreement Between Prospective and Retrospective Measures of Childhood Maltreatment
2019Co-Authors: Baldwin, Aaron Reuben, Joanne B. Newbury, Andrea DaneseAbstract:Importance: Childhood Maltreatment is associated with mental illness. Researchers, clinicians, and public health professionals use prospective or retrospective measures interchangeably to assess Childhood Maltreatment, assuming that the 2 measures identify the same individuals. However, this assumption has not been comprehensively tested. / Objective: To meta-analyze the agreement between prospective and retrospective measures of Childhood Maltreatment. / Data Sources: MEDLINE, PsycINFO, Embase, and Sociological Abstracts were searched for peer-reviewed, English-language articles from inception through January 1, 2018. Search terms included child* Maltreatment, child* abuse, child* neglect, child bull*, child* trauma, child* advers*, and early life stress combined with prospective* and cohort. / Study Selection: Studies with prospective measures of Childhood Maltreatment were first selected. Among the selected studies, those with corresponding retrospective measures of Maltreatment were identified. Of 450 studies with prospective measures of Childhood Maltreatment, 16 had paired retrospective data to compute the Cohen κ coefficient. / Data Extraction and Synthesis: Multiple investigators independently extracted data according to PRISMA and MOOSE guidelines. Random-effects meta-analyses were used to pool the results and test predictors of heterogeneity. / Main Outcomes and Measures: The primary outcome was the agreement between prospective and retrospective measures of Childhood Maltreatment, expressed as a κ coefficient. Moderators of agreement were selected a priori and included the measure used for prospective or retrospective assessment of Childhood Maltreatment, age at retrospective report, sample size, sex distribution, and study quality. / Results: Sixteen unique studies including 25 471 unique participants (52.4% female [SD, 10.6%]; mean [SD] age, 30.6 [11.6] years) contained data on the agreement between prospective and retrospective measures of Childhood Maltreatment. The agreement between prospective and retrospective measures of Childhood Maltreatment was poor, with κ = 0.19 (95% CI, 0.14-0.24; P
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Agreement Between Prospective and Retrospective Measures of Childhood Maltreatment: A Systematic Review and Meta-analysis
JAMA psychiatry, 2019Co-Authors: Jessie R. Baldwin, Aaron Reuben, Joanne B. Newbury, Andrea DaneseAbstract:Importance Childhood Maltreatment is associated with mental illness. Researchers, clinicians, and public health professionals use prospective or retrospective measures interchangeably to assess Childhood Maltreatment, assuming that the 2 measures identify the same individuals. However, this assumption has not been comprehensively tested. Objective To meta-analyze the agreement between prospective and retrospective measures of Childhood Maltreatment. Data Sources MEDLINE, PsycINFO, Embase, and Sociological Abstracts were searched for peer-reviewed, English-language articles from inception through January 1, 2018. Search terms includedchild* Maltreatment,child* abuse,child* neglect,child bull*,child* trauma,child* advers*, andearly life stresscombined withprospective*andcohort. Study Selection Studies with prospective measures of Childhood Maltreatment were first selected. Among the selected studies, those with corresponding retrospective measures of Maltreatment were identified. Of 450 studies with prospective measures of Childhood Maltreatment, 16 had paired retrospective data to compute the Cohen κ coefficient. Data Extraction and Synthesis Multiple investigators independently extracted data according to PRISMA and MOOSE guidelines. Random-effects meta-analyses were used to pool the results and test predictors of heterogeneity. Main Outcomes and Measures The primary outcome was the agreement between prospective and retrospective measures of Childhood Maltreatment, expressed as a κ coefficient. Moderators of agreement were selected a priori and included the measure used for prospective or retrospective assessment of Childhood Maltreatment, age at retrospective report, sample size, sex distribution, and study quality. Results Sixteen unique studies including 25 471 unique participants (52.4% female [SD, 10.6%]; mean [SD] age, 30.6 [11.6] years) contained data on the agreement between prospective and retrospective measures of Childhood Maltreatment. The agreement between prospective and retrospective measures of Childhood Maltreatment was poor, with κ = 0.19 (95% CI, 0.14-0.24; P Conclusions and Relevance Prospective and retrospective measures of Childhood Maltreatment identify different groups of individuals. Therefore, children identified prospectively as having experienced Maltreatment may have different risk pathways to mental illness than adults retrospectively reporting Childhood Maltreatment. Researchers, clinicians, and public health care professionals should recognize these critical measurement differences when conducting research into Childhood Maltreatment and developing interventions.
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Elevated inflammation levels in depressed adults with a history of Childhood Maltreatment.
Archives of general psychiatry, 2008Co-Authors: Andrea Danese, Carmine M. Pariante, Richie Poulton, Terrie E. Moffitt, Antony Ambler, Avshalom CaspiAbstract:CONTEXT: The association between depression and inflammation is inconsistent across research samples. OBJECTIVE: To test whether a history of Childhood Maltreatment could identify a subgroup of depressed individuals with elevated inflammation levels, thus helping to explain previous inconsistencies. DESIGN: Prospective longitudinal cohort study. SETTING: New Zealand. PARTICIPANTS: A representative birth cohort of 1000 individuals was followed up to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Study members were assessed for history of Childhood Maltreatment and current depression. MAIN OUTCOME MEASURES: Inflammation was assessed using a clinically relevant categorical measure of high-sensitivity C-reactive protein (>3 mg/L) and a dimensional inflammation factor indexing the shared variance of continuous measures of high-sensitivity C-reactive protein, fibrinogen, and white blood cells. RESULTS: Although depression was associated with high levels of high-sensitivity C-reactive protein (relative risk,1.45; 95% confidence interval,1.06-1.99), this association was significantly attenuated and no longer significant when the effect of Childhood Maltreatment was taken into account. Individuals with current depression and a history of Childhood Maltreatment were more likely to have high levels of high-sensitivity C-reactive protein compared with control subjects (n = 27; relative risk, 2.07; 95% confidence interval, 1.23-3.47). In contrast, individuals with current depression only had a nonsignificant elevation in risk (n = 109; relative risk, 1.40; 95% confidence interval, 0.97-2.01). Results were generalizable to the inflammation factor. The elevated inflammation levels in individuals who were both depressed and maltreated were not explained by correlated risk factors such as depression recurrence, low socioeconomic status in Childhood or adulthood, poor health, or smoking. CONCLUSIONS: A history of Childhood Maltreatment contributes to the co-occurrence of depression and inflammation. Information about experiences of Childhood Maltreatment may help to identify depressed individuals with elevated inflammation levels and, thus, at greater risk of cardiovascular disease. Language: en
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Childhood Maltreatment predicts adult inflammation in a life course study
Proceedings of the National Academy of Sciences of the United States of America, 2007Co-Authors: Andrea Danese, Carmine M. Pariante, Avshalom Caspi, Alan Taylor, Richie PoultonAbstract:Stress in early life has been associated with insufficient glucocorticoid signaling in adulthood, possibly affecting inflammation processes. Childhood Maltreatment has been linked to increased risk of adult disease with potential inflammatory origin. However, the impact of early life stress on adult inflammation is not known in humans. We tested the life-course association between Childhood Maltreatment and adult inflammation in a birth cohort followed to age 32 years as part of the Dunedin Multidisciplinary Health and Development Study. Regression models were used to estimate the effect of Maltreatment on inflammation, adjusting for co-occurring risk factors and potential mediating variables. Maltreated children showed a significant and graded increase in the risk for clinically relevant C-reactive protein levels 20 years later, in adulthood [risk ratio (RR) = 1.80, 95% confidence interval (CI) = 1.26–2.58]. The effect of Childhood Maltreatment on adult inflammation was independent of the influence of co-occurring early life risks (RR = 1.58, 95% CI = 1.08–2.31), stress in adulthood (RR = 1.64, 95% CI = 1.12–2.39), and adult health and health behavior (RR = 1.76, 95% CI = 1.23–2.51). More than 10% of cases of low-grade inflammation in the population, as indexed by high C-reactive protein, may be attributable to Childhood Maltreatment. The association between Maltreatment and adult inflammation also generalizes to fibrinogen and white blood cell count. Childhood Maltreatment is a previously undescribed, independent, and preventable risk factor for inflammation in adulthood. Inflammation may be an important developmental mediator linking adverse experiences in early life to poor adult health.
Deborah S. Hasin - One of the best experts on this subject based on the ideXlab platform.
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Childhood Maltreatment, stressful life events, and alcohol craving in adult drinkers
Alcoholism clinical and experimental research, 2014Co-Authors: June H. Kim, Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Melanie M. Wall, Bridget F. Grant, Silvia S. Martins, Dvora Shmulewitz, Julian Santaella, Deborah S. HasinAbstract:Background Little is known about the relationship between stressful life events and alcohol craving in the general population, and whether a history of Childhood Maltreatment sensitizes individuals to crave alcohol after adult stressors. Methods Participants were 22,147 past-year drinkers from Wave 2 (2004 to 2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. A structured, face-to-face interview assessed past-year stressful life events, alcohol craving, and history of Childhood Maltreatment. Logistic regression was used to generate adjusted odds ratios (aOR) to evaluate the relationship between stressful life events and craving, adjusting for demographic characteristics and parental history of alcoholism. Interaction between stressful life events and Childhood Maltreatment was also assessed. Results Compared to participants with no stressful life events, those with ≥3 events had increased odds of moderate alcohol craving (aOR = 3.15 [95% CI = 2.30 to 4.33]) and severe craving (aOR = 8.47 [95% CI = 4.78 to 15.01]). Stressful life events and Childhood Maltreatment interacted in predicting severe craving (p = 0.017); those with ≥3 events were at higher risk of craving if they had been exposed to Childhood Maltreatment. Conclusions A direct relationship between stressful life events and risk of alcohol craving was observed. Further, history of Childhood Maltreatment increased the salience of stressful life events in adulthood. Future studies should examine the role of psychiatric comorbidity in more complex models of stress sensitization and alcohol craving.
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Childhood Maltreatment and the structure of common psychiatric disorders
British Journal of Psychiatry, 2012Co-Authors: Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Katie A. Mclaughlin, Melanie M. Wall, Bridget F. Grant, Deborah S. HasinAbstract:Background Previous research suggests that various types of Childhood Maltreatment frequently co-occur and confer risk for multiple psychiatric diagnoses. This non-specific pattern of risk may mean that Childhood Maltreatment increases vulnerability to numerous specific psychiatric disorders through diverse, specific mechanisms or that Childhood Maltreatment engenders a generalised liability to dimensions of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically. Aims We used a latent variable approach to estimate the associations of Childhood Maltreatment with underlying dimensions of internalising and externalising psychopathology and with specific disorders after accounting for the latent dimensions. We also examined gender differences in these associations. Method Data were drawn from a nationally representative survey of 34 653 US adults. Lifetime DSM-IV psychiatric disorders were assessed using the AUDADIS-IV. Physical, sexual and emotional abuse and neglect were assessed using validated measures. Analyses controlled for other Childhood adversities and sociodemographics. Results The effects were fully mediated through the latent liability dimensions, with an impact on underlying liability levels to internalising and externalising psychopathology rather than specific psychiatric disorders. Important gender differences emerged with physical abuse associated only with externalising liability in men, and only with internalising liability in women. Neglect was not significantly associated with latent liability levels. Conclusions The association between Childhood Maltreatment and common psychiatric disorders operates through latent liabilities to experience internalising and externalising psychopathology, indicating that the prevention of Maltreatment may have a wide range of benefits in reducing the prevalence of many common mental disorders. Different forms of abuse have gender-specific consequences for the expression of internalising and externalising psychopathology, suggesting gender-specific aetiological pathways between Maltreatment and psychopathology.
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Childhood Maltreatment and the structure of common psychiatric disorders
The British journal of psychiatry : the journal of mental science, 2011Co-Authors: Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Katie A. Mclaughlin, Melanie M. Wall, Bridget F. Grant, Deborah S. HasinAbstract:Previous research suggests that various types of Childhood Maltreatment frequently co-occur and confer risk for multiple psychiatric diagnoses. This non-specific pattern of risk may mean that Childhood Maltreatment increases vulnerability to numerous specific psychiatric disorders through diverse, specific mechanisms or that Childhood Maltreatment engenders a generalised liability to dimensions of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically.
Karmel W. Choi - One of the best experts on this subject based on the ideXlab platform.
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Genomic influences on self-reported Childhood Maltreatment
Translational psychiatry, 2020Co-Authors: Shareefa Dalvie, Adam X. Maihofer, Jonathan R. I. Coleman, Bekh Bradley, Gerome Breen, Leslie A. Brick, Chia-yen Chen, Karmel W. Choi, Laramie E. Duncan, Guia GuffantiAbstract: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 (h2snp), (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). h2snp 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. h2snp 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 (rg = 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.
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Genomic Influences on Self-Reported Childhood Maltreatment
2019Co-Authors: Shareefa Dalvie, Adam X. Maihofer, Jonathan R. I. Coleman, Bekh Bradley, Gerome Breen, Leslie A. Brick, Chia-yen Chen, Karmel W. Choi, Laramie E. Duncan, Guia GuffantiAbstract: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 reported Childhood Maltreatment, 2) calculate the relevant SNP-based heritability estimates, and 3) quantify the genetic overlap of reported Childhood Maltreatment with mental and physical health-related phenotypes. 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 working group (PGC-PTSD) (n=26,290). Heritability estimations for Childhood Maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression (LDSR). Two genome-wide significant loci associated with Childhood Maltreatment, located on chromosomes 3p13 (rs142346759, beta=0.015, p=4.35×10−8, FOXP1) and 7q31.1 (rs10262462, beta=-0.016, p=3.24×10−8, FOXP2), were identified in the discovery dataset but were not replicated in the PGC-PTSD sample. SNP-based heritability for Childhood Maltreatment was estimated to be ∼6%. Childhood Maltreatment was most significantly genetically correlated with depressive symptoms (rg=0.70, p=4.65×10−40). This is the first large-scale genetic study to identify specific variants associated with self-reported Childhood Maltreatment. FOXP genes could influence traits such as depression and thereby 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 various psychiatric disorders, may ultimately be useful in in developing targeted treatment and prevention strategies.
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Childhood Maltreatment and Perinatal Mood and Anxiety Disorders A Systematic Review
Trauma violence & abuse, 2015Co-Authors: Karmel W. Choi, Kathleen J. SikkemaAbstract:Perinatal mood and anxiety disorders (PMADs) compromise maternal and child well-being and may be influenced by traumatic experiences across the life course. A potent and common form of trauma is Childhood Maltreatment, but its specific impact on PMADs is not well understood. A systematic review was undertaken to synthesize empirical literature on the relationship between maternal histories of Childhood Maltreatment and PMADs. Of the 876 citations retrieved, 35 reports from a total of 26,239 participants met inclusion criteria, documenting substantial rates of Childhood Maltreatment and PMADs. Robust trends of association were observed between Childhood Maltreatment and perinatal depression, as well as post-traumatic stress disorder, but findings for anxiety were less consistent. Examining multivariate results suggested that Childhood Maltreatment predicts PMADs above and beyond sociodemographic, psychiatric, perinatal, and psychosocial factors, but may also be partially mediated by variables such as later...
Melanie M. Wall - One of the best experts on this subject based on the ideXlab platform.
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Childhood Maltreatment and risk of suicide attempt: a nationally representative study.
The Journal of clinical psychiatry, 2015Co-Authors: Nicolas Hoertel, Melanie M. Wall, Silvia Franco, Maria A. Oquendo, Shuai Wang, Frédéric Limosin, Carlos BlancoAbstract:BACKGROUND: Previous research suggests that various types of Childhood Maltreatment frequently co-occur and confer risk for attempting suicide. However, it is unknown whether the effect of Childhood Maltreatment on this risk occurs through diverse, specific mechanisms or through a generalized liability, independently of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically. METHOD: Structural equation modeling was used to examine the effect of different types of Childhood Maltreatment (ie, sexual abuse, physical and emotional abuse and neglect) on suicide attempt risk, and on age at first suicide attempt and repeated suicide attempts among attempters. Analyses controlled for demographic characteristics and DSM-IV Axis I and Axis II disorders. Data were drawn from a nationally representative survey of US adults, the 2004-2005 National Epidemiologic Survey on Alcohol and Related Conditions (N = 34,653). RESULTS: Childhood Maltreatment was associated with an increased risk for attempting suicide and an earlier age at first suicide attempt among attempters, independently of psychopathology (P .05). CONCLUSIONS: The association between Childhood Maltreatment and suicide attempt operates mainly through a single broad liability, suggesting that the mechanisms underlying this dimension should be considered as an important therapeutic target for suicide prevention. Language: en
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Childhood Maltreatment, stressful life events, and alcohol craving in adult drinkers
Alcoholism clinical and experimental research, 2014Co-Authors: June H. Kim, Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Melanie M. Wall, Bridget F. Grant, Silvia S. Martins, Dvora Shmulewitz, Julian Santaella, Deborah S. HasinAbstract:Background Little is known about the relationship between stressful life events and alcohol craving in the general population, and whether a history of Childhood Maltreatment sensitizes individuals to crave alcohol after adult stressors. Methods Participants were 22,147 past-year drinkers from Wave 2 (2004 to 2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. A structured, face-to-face interview assessed past-year stressful life events, alcohol craving, and history of Childhood Maltreatment. Logistic regression was used to generate adjusted odds ratios (aOR) to evaluate the relationship between stressful life events and craving, adjusting for demographic characteristics and parental history of alcoholism. Interaction between stressful life events and Childhood Maltreatment was also assessed. Results Compared to participants with no stressful life events, those with ≥3 events had increased odds of moderate alcohol craving (aOR = 3.15 [95% CI = 2.30 to 4.33]) and severe craving (aOR = 8.47 [95% CI = 4.78 to 15.01]). Stressful life events and Childhood Maltreatment interacted in predicting severe craving (p = 0.017); those with ≥3 events were at higher risk of craving if they had been exposed to Childhood Maltreatment. Conclusions A direct relationship between stressful life events and risk of alcohol craving was observed. Further, history of Childhood Maltreatment increased the salience of stressful life events in adulthood. Future studies should examine the role of psychiatric comorbidity in more complex models of stress sensitization and alcohol craving.
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Childhood Maltreatment and the structure of common psychiatric disorders
British Journal of Psychiatry, 2012Co-Authors: Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Katie A. Mclaughlin, Melanie M. Wall, Bridget F. Grant, Deborah S. HasinAbstract:Background Previous research suggests that various types of Childhood Maltreatment frequently co-occur and confer risk for multiple psychiatric diagnoses. This non-specific pattern of risk may mean that Childhood Maltreatment increases vulnerability to numerous specific psychiatric disorders through diverse, specific mechanisms or that Childhood Maltreatment engenders a generalised liability to dimensions of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically. Aims We used a latent variable approach to estimate the associations of Childhood Maltreatment with underlying dimensions of internalising and externalising psychopathology and with specific disorders after accounting for the latent dimensions. We also examined gender differences in these associations. Method Data were drawn from a nationally representative survey of 34 653 US adults. Lifetime DSM-IV psychiatric disorders were assessed using the AUDADIS-IV. Physical, sexual and emotional abuse and neglect were assessed using validated measures. Analyses controlled for other Childhood adversities and sociodemographics. Results The effects were fully mediated through the latent liability dimensions, with an impact on underlying liability levels to internalising and externalising psychopathology rather than specific psychiatric disorders. Important gender differences emerged with physical abuse associated only with externalising liability in men, and only with internalising liability in women. Neglect was not significantly associated with latent liability levels. Conclusions The association between Childhood Maltreatment and common psychiatric disorders operates through latent liabilities to experience internalising and externalising psychopathology, indicating that the prevention of Maltreatment may have a wide range of benefits in reducing the prevalence of many common mental disorders. Different forms of abuse have gender-specific consequences for the expression of internalising and externalising psychopathology, suggesting gender-specific aetiological pathways between Maltreatment and psychopathology.
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Childhood Maltreatment and the structure of common psychiatric disorders
The British journal of psychiatry : the journal of mental science, 2011Co-Authors: Katherine M. Keyes, Nicholas R. Eaton, Robert F. Krueger, Katie A. Mclaughlin, Melanie M. Wall, Bridget F. Grant, Deborah S. HasinAbstract:Previous research suggests that various types of Childhood Maltreatment frequently co-occur and confer risk for multiple psychiatric diagnoses. This non-specific pattern of risk may mean that Childhood Maltreatment increases vulnerability to numerous specific psychiatric disorders through diverse, specific mechanisms or that Childhood Maltreatment engenders a generalised liability to dimensions of psychopathology. Although these competing explanations have different implications for intervention, they have never been evaluated empirically.
Guia Guffanti - One of the best experts on this subject based on the ideXlab platform.
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Genomic influences on self-reported Childhood Maltreatment
Translational psychiatry, 2020Co-Authors: Shareefa Dalvie, Adam X. Maihofer, Jonathan R. I. Coleman, Bekh Bradley, Gerome Breen, Leslie A. Brick, Chia-yen Chen, Karmel W. Choi, Laramie E. Duncan, Guia GuffantiAbstract: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 (h2snp), (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). h2snp 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. h2snp 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 (rg = 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.
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Genomic Influences on Self-Reported Childhood Maltreatment
2019Co-Authors: Shareefa Dalvie, Adam X. Maihofer, Jonathan R. I. Coleman, Bekh Bradley, Gerome Breen, Leslie A. Brick, Chia-yen Chen, Karmel W. Choi, Laramie E. Duncan, Guia GuffantiAbstract: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 reported Childhood Maltreatment, 2) calculate the relevant SNP-based heritability estimates, and 3) quantify the genetic overlap of reported Childhood Maltreatment with mental and physical health-related phenotypes. 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 working group (PGC-PTSD) (n=26,290). Heritability estimations for Childhood Maltreatment and genetic correlations with mental/physical health traits were calculated using linkage disequilibrium score regression (LDSR). Two genome-wide significant loci associated with Childhood Maltreatment, located on chromosomes 3p13 (rs142346759, beta=0.015, p=4.35×10−8, FOXP1) and 7q31.1 (rs10262462, beta=-0.016, p=3.24×10−8, FOXP2), were identified in the discovery dataset but were not replicated in the PGC-PTSD sample. SNP-based heritability for Childhood Maltreatment was estimated to be ∼6%. Childhood Maltreatment was most significantly genetically correlated with depressive symptoms (rg=0.70, p=4.65×10−40). This is the first large-scale genetic study to identify specific variants associated with self-reported Childhood Maltreatment. FOXP genes could influence traits such as depression and thereby 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 various psychiatric disorders, may ultimately be useful in in developing targeted treatment and prevention strategies.