Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

Testing the causal relationships of physical activity and sedentary behaviour with mental health and substance use disorders: a Mendelian randomisation study.

Observational studies suggest that physical activity can reduce the risk of mental health and substance use disorders. However, it is unclear whether this relationship is causal or explained by confounding bias (e.g., common underlying causes or reverse causality). We investigated the bidirectional causal relationship of physical activity (PA) and sedentary behaviour (SB) with ten mental health and substance use disorders, applying two-sample Mendelian Randomisation (MR). Genetic instruments for the exposures and outcomes were derived from the largest available, non-overlapping genome-wide association studies (GWAS). Summary-level data for objectively assessed PA (accelerometer-based average activity, moderate activity, and walking) and SB and self-reported moderate-to-vigorous PA were obtained from the UK Biobank. Data for mental health/substance use disorders were obtained from the Psychiatric Genomics Consortium and the GWAS and Sequencing Consortium of Alcohol and Nicotine Use. MR estimates were combined using inverse variance weighted meta-analysis (IVW). Sensitivity analyses were conducted to assess the robustness of the results. Accelerometer-based average PA was associated with a lower risk of depression (b = -0.043, 95% CI: -0.071 to -0.016, effect size[OR] = 0.957) and cigarette smoking (b = -0.026; 95% CI: -0.035 to -0.017, effect size[ß] = -0.022). Accelerometer-based SB decreased the risk of anorexia (b = -0.341, 95% CI: -0.530 to -0.152, effect size[OR] = 0.711) and schizophrenia (b = -0.230; 95% CI: -0.285 to -0.175, effect size[OR] = 0.795). However, we found evidence of reverse causality in the relationship between SB and schizophrenia. Further, PTSD, bipolar disorder, anorexia, and ADHD were all associated with increased PA. This study provides evidence consistent with a causal protective effect of objectively assessed but not self-reported PA on reduced depression and cigarette smoking. Objectively assessed SB had a protective relationship with anorexia. Enhancing PA may be an effective intervention strategy to reduce depressive symptoms and addictive behaviours, while promoting sedentary or light physical activities may help to reduce the risk of anorexia in at-risk individuals.

Research Review: Why do prospective and retrospective measures of maltreatment differ? A narrative review.

BACKGROUND: Childhood maltreatment contributes to a large mental health burden worldwide. Different measures of childhood maltreatment are not equivalent and may capture meaningful differences. In particular, prospective and retrospective measures of maltreatment identify different groups of individuals and are differentially associated with psychopathology. However, the reasons behind these discrepancies have not yet been comprehensively mapped. METHODS: In this review, we draw on multi-disciplinary research and present an integrated framework to explain maltreatment measurement disagreement. RESULTS: We identified three interrelated domains. First, methodological issues related to measurement and data collection methods. Second, the role of memory in influencing retrospective reports of maltreatment. Finally, the motivations individuals may have to disclose, withhold, or fabricate information about maltreatment. CONCLUSIONS: A greater understanding of maltreatment measurement disagreement may point to new ways to conceptualise and assess maltreatment. Furthermore, it may help uncover mechanisms underlying maltreatment-related psychopathology and targets for novel interventions.

The relationship between type, timing and duration of exposure to adverse childhood experiences and adolescent self-harm and depression: findings from three UK prospective population-based cohorts.

BACKGROUND: Adverse childhood experiences (ACEs) are well-established risk factors for self-harm and depression. However, despite their high comorbidity, there has been little focus on the impact of developmental timing and the duration of exposure to ACEs on co-occurring self-harm and depression. METHODS: Data were utilised from over 22,000 children and adolescents participating in three UK cohorts, followed up longitudinally for 14-18 years: the Avon Longitudinal Study of Parents and Children (ALSPAC), the Millennium Cohort Study (MCS) and the Environmental Risk (E-Risk) Longitudinal Twin Study. Multinomial logistic regression models estimated associations between each ACE type and a four-category outcome: no self-harm or depression, self-harm alone, depression alone and self-harm with co-occurring depression. A structured life course modelling approach was used to examine whether the accumulation (duration) of exposure to each ACE, or a critical period (timing of ACEs) had the strongest effects on self-harm and depression in adolescence. RESULTS: The majority of ACEs were associated with co-occurring self-harm and depression, with consistent findings across cohorts. The importance of timing and duration of ACEs differed across ACEs and across cohorts. For parental mental health problems, longer duration of exposure was strongly associated with co-occurring self-harm and depression in both ALSPAC (adjusted OR: 1.18, 95% CI: 1.10-1.25) and MCS (1.18, 1.11-1.26) cohorts. For other ACEs in ALSPAC, exposure in middle childhood was most strongly associated with co-occurring self-harm and depression, and ACE occurrence in early childhood and adolescence was more important in the MCS. CONCLUSIONS: Efforts to mitigate the impact of ACEs should start in early life with continued support throughout childhood, to prevent long-term exposure to ACEs contributing to risk of self-harm and depression in adolescence.

Social isolation and poor mental health in young people: testing genetic and environmental influences in a longitudinal cohort study.

We assessed genetic and environmental influences on social isolation across childhood and the overlap between social isolation and mental health symptoms including depression symptoms, conduct problems, and psychotic-like experiences from adolescence to young adulthood. Participants included 2,232 children from the Environmental Risk Longitudinal Twin Study. Social isolation was measured at ages 5, 7, 10, 12, and 18. A Cholesky decomposition was specified to estimate the genetic and environmental influences on social isolation across ages 5, 7, 10, and 12. An independent pathway model was used to assess additive genetic (A), shared environmental (C), and non-shared environmental (E) influences on the overlap between social isolation and mental health problems from age 12 to 18. Genetic and non-shared environmental influences accounted for half of the variance in childhood social isolation. Genetic influences contributed to the continuity of social isolation across childhood, while non-shared environmental influences were age-specific. The longitudinal overlap between social isolation and mental health symptoms was largely explained by genetic influences for depression symptoms (r = 0.15-0.24: 82-84% A, 11-12% C, and 5-6% E) and psychotic-like experiences (r = 0.13-0.15: 81-91% A, 0-8% C, and 9-11% E) but not conduct problems (r = 0.13-0.16; 0-42% A, 42-81% C, 16-24% E). Our findings emphasise that rather than a risk factor or an outcome, social isolation is aetiologically intertwined with the experience of poor mental health. An integrative assessment of social isolation could be a helpful indicator of underlying mental health symptoms in young people.

PRAME Updated: Diagnostic, Prognostic, and Therapeutic Role in Skin Cancer.

Preferentially Expressed Antigen in Melanoma (PRAME), a member of the cancer/testis antigen family, is central to the field of skin cancer diagnostics and therapeutics. As a nuclear receptor and transcriptional regulator, PRAME plays a critical role in inhibiting retinoic acid signalling, which is essential for cell differentiation and proliferation. Its aberrant overexpression in various malignancies, particularly cutaneous melanoma, is associated with more aggressive tumour phenotypes, positioning PRAME as both a diagnostic and prognostic marker. In melanoma, PRAME is typically highly expressed, in contrast to its weak or absent expression in benign nevi, thereby improving the accuracy of differential diagnoses. The diagnostic value of PRAME extends to various lesions. It is significantly expressed in uveal melanoma, correlating to an increased risk of metastasis. In acral melanomas, especially those with histopathological ambiguity, PRAME helps to improve diagnostic accuracy. However, its expression in spitzoid and ungual melanocytic lesions is inconsistent and requires a comprehensive approach for an accurate assessment. In soft tissue sarcomas, PRAME may be particularly helpful in differentiating melanoma from clear cell sarcoma, an important distinction due to their similar histological appearance but different treatment approaches and prognosis, or in detecting dedifferentiated and undifferentiated melanomas. In non-melanoma skin cancers such as basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma, the variable expression of PRAME can lead to diagnostic complexity. Despite these challenges, the potential of PRAME as a therapeutic target in melanoma is significant. Emerging immunotherapies, including T-cell-based therapies and vaccines targeting PRAME, are being investigated to exploit its cancer-specific expression. Ongoing research into the molecular role and mechanism of action of PRAME in skin cancer continues to open new avenues in both diagnostics and therapeutics, with the potential to transform the management of melanoma and related skin cancers.

Clinical prediction models in psychiatry: a systematic review of two decades of progress and challenges.

Recent years have seen the rapid proliferation of clinical prediction models aiming to support risk stratification and individualized care within psychiatry. Despite growing interest, attempts to synthesize current evidence in the nascent field of precision psychiatry have remained scarce. This systematic review therefore sought to summarize progress towards clinical implementation of prediction modeling for psychiatric outcomes. We searched MEDLINE, PubMed, Embase, and PsychINFO databases from inception to September 30, 2020, for English-language articles that developed and/or validated multivariable models to predict (at an individual level) onset, course, or treatment response for non-organic psychiatric disorders (PROSPERO: CRD42020216530). Individual prediction models were evaluated based on three key criteria: (i) mitigation of bias and overfitting; (ii) generalizability, and (iii) clinical utility. The Prediction model Risk Of Bias ASsessment Tool (PROBAST) was used to formally appraise each study's risk of bias. 228 studies detailing 308 prediction models were ultimately eligible for inclusion. 94.5% of developed prediction models were deemed to be at high risk of bias, largely due to inadequate or inappropriate analytic decisions. Insufficient internal validation efforts (within the development sample) were also observed, while only one-fifth of models underwent external validation in an independent sample. Finally, our search identified just one published model whose potential utility in clinical practice was formally assessed. Our findings illustrated significant growth in precision psychiatry with promising progress towards real-world application. Nevertheless, these efforts have been inhibited by a preponderance of bias and overfitting, while the generalizability and clinical utility of many published models has yet to be formally established. Through improved methodological rigor during initial development, robust evaluations of reproducibility via independent validation, and evidence-based implementation frameworks, future research has the potential to generate risk prediction tools capable of enhancing clinical decision-making in psychiatric care.

A multivariate genetic analysis of anxiety sensitivity, environmental sensitivity and reported life events in adolescents.

BACKGROUND: Despite being considered a measure of environmental risk, reported life events are partly heritable. One mechanism that may contribute to this heritability is genetic influences on sensitivity, relating to how individuals process and interpret internal and external signals. The aim of this study was to explore the genetic and environmental overlap between self-reported life events and measures of sensitivity. METHODS: At age 17, 2,939 individuals from the Twins Early Development Study (TEDS) completed measures of anxiety sensitivity (Children's Anxiety Sensitivity Index), environmental sensitivity (Highly Sensitive Child Scale) and reported their experience of 20 recent life events. Using multivariate Cholesky decomposition models, we investigated the shared genetic and environmental influences on the associations between these measures of sensitivity and the number of reported life events, as well as both negative and positive ratings of life events. RESULTS: The majority of the associations between anxiety sensitivity, environmental sensitivity and reported life events were explained by shared genetic influences (60%-75%), with the remainder explained by nonshared environmental influences (25%-40%). Environmental sensitivity showed comparable genetic correlations with both negative and positive ratings of life events (rA  = .21 and .15), anxiety sensitivity only showed a significant genetic correlation with negative ratings of life events (rA  = .33). Approximately 10% of the genetic influences on reported life events were accounted for by influences shared with anxiety sensitivity and environmental sensitivity. CONCLUSION: Differences in how individuals process the contextual aspects of the environment or interpret their own physical and emotional response to environmental stimuli may be one mechanism through which genetic liability influences the subjective experience of life events.

Characteristics of complex posttraumatic stress disorder (PTSD) in young people with PTSD following multiple trauma exposure.

BACKGROUND: Complex PTSD (CPTSD) is a relatively new diagnosis. The objective of the present study was to investigate how trauma characteristics, comorbid psychopathology and cognitive and social factors experienced by children and adolescents with a posttraumatic stress disorder (PTSD) diagnosis following exposure to multiple traumatic events differs between those who meet the criteria for CPTSD and those who do not. METHOD: The present research used baseline data from the DECRYPT trial (BMJ Open, 2021, 11, e047600). Participants (n = 120) were aged 8-17 years and had exposure to multiple traumas and a PTSD diagnosis. The data collected comprised self-report and parent/caregiver-report questionnaires and interviews. Three primary analyses were conducted, comparing number of trauma types, prevalence of sexual trauma and prevalence of intrafamilial abuse between the CPTSD and PTSD-only groups. A range of comorbid psychopathology and cognitive and social factors were compared between the groups in an exploratory secondary analysis. All analyses were preregistered. RESULTS: The CPTSD group (n = 72, 60%) had a significantly higher frequency of sexual trauma than the PTSD-only group (n = 48, 40%). The groups did not significantly differ on number of trauma types or prevalence of intrafamilial abuse. From the secondary analysis, the CPTSD group were found to have significantly higher scores on measures of negative post-traumatic cognitions, depression and panic. These results were replicated in correlation analyses using a continuous measure of CPTSD symptoms. CONCLUSIONS: A large proportion of youth exposed to multiple traumatic events met criteria for CPTSD. Sexual trauma appears to be related to CPTSD symptoms. Youth with CPTSD appear to have greater severity of comorbid depression and panic symptoms, as well as more negative post-traumatic cognitions. Further investigation could focus on the directionality and mechanisms for these associations.

The developmental course of loneliness in adolescence: Implications for mental health, educational attainment, and psychosocial functioning.

The present study examined patterns of stability and change in loneliness across adolescence. Data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative cohort of 2,232 individuals born in 1994 and 1995. Loneliness was assessed when participants were aged 12 and 18. Loneliness showed modest stability across these ages (r = .25). Behavioral genetic modeling indicated that stability in loneliness was explained largely by genetic influences (66%), while change was explained by nonshared environmental effects (58%). Individuals who reported loneliness at both ages were broadly similar to individuals who only reported it at age 18, with both groups at elevated risk of mental health problems, physical health risk behaviors, and education and employment difficulties. Individuals who were lonely only at age 12 generally fared better; however, they were still more likely to finish school with lower qualifications. Positive family influences in childhood predicted reduced risk of loneliness at age 12, while negative peer experiences increased the risk. Together, the findings show that while early adolescent loneliness does not appear to exert a cumulative burden when it persists, it is nonetheless a risk for a range of concomitant impairments, some of which can endure.

Adolescents' perceptions of family social status correlate with health and life chances: A twin difference longitudinal cohort study.

Children from lower-income households are at increased risk for poor health, educational failure, and behavioral problems. This social gradient is one of the most reproduced findings in health and social science. How people view their position in social hierarchies also signals poor health. However, when adolescents' views of their social position begin to independently relate to well-being is currently unknown. A cotwin design was leveraged to test whether adolescents with identical family backgrounds, but who viewed their family's social status as higher than their same-aged and sex sibling, experienced better well-being in early and late adolescence. Participants were members of the Environmental Risk Longitudinal Twin Study, a representative cohort of British twins (n = 2,232) followed across the first 2 decades of life. By late adolescence, perceptions of subjective family social status (SFSS) robustly correlated with multiple indicators of health and well-being, including depression; anxiety; conduct problems; marijuana use; optimism; not in education, employment, or training (NEET) status; and crime. Findings held controlling for objective socioeconomic status both statistically and by cotwin design after accounting for measures of childhood intelligence (IQ), negative affect, and prior mental health risk and when self-report, informant report, and administrative data were used. Little support was found for the biological embedding of adolescents' perceptions of familial social status as indexed by inflammatory biomarkers or cognitive tests in late adolescence or for SFSS in early adolescence as a robust correlate of well-being or predictor of future problems. Future experimental studies are required to test whether altering adolescents' subjective social status will lead to improved well-being and social mobility.

New directions in research on childhood adversity.

Childhood adversities are major preventable risk factors for poor mental and physical health. Scientific advances in this area are not matched by clinical gains for affected individuals. We reflect on novel research directions that could accelerate clinical impact.

Genetic and early environmental predictors of adulthood self-reports of trauma.

BACKGROUND: Retrospective self-reports of childhood trauma are associated with a greater risk of psychopathology in adulthood than prospective measures of trauma. Heritable reporter characteristics are anticipated to account for part of this association, whereby genetic predisposition to certain traits influences both the likelihood of self-reporting trauma and of developing psychopathology. However, previous research has not considered how gene-environment correlation influences these associations. AIMS: To investigate reporter characteristics associated with retrospective self-reports of childhood trauma and whether these associations are accounted for by gene-environment correlation. METHOD: In 3963 unrelated individuals from the Twins Early Development Study, we tested whether polygenic scores for 21 psychiatric, cognitive, anthropometric and personality traits were associated with retrospectively self-reported childhood emotional and physical abuse. To assess the presence of gene-environment correlation, we investigated whether these associations remained after controlling for composite scores of environmental adversity across development. RESULTS: Retrospectively self-reported childhood trauma was associated with polygenic scores for autism spectrum disorder (ASD), body mass index (BMI), post-traumatic stress disorder (PTSD) and risky behaviours. When composite scores of environmental adversity were controlled for, only associations with the polygenic scores for ASD and PTSD remained significant. CONCLUSIONS: Genetic predisposition to ASD and PTSD may increase liability to experiencing or interpreting events as traumatic. Associations between genetic predisposition for risky behaviour and BMI with self-reported childhood trauma may reflect gene-environment correlation. Studies of the association between retrospectively self-reported childhood trauma and later-life outcomes should consider that genetically influenced reporter characteristics may confound associations, both directly and through gene-environment correlation.

Mother's and children's ADHD genetic risk, household chaos and children's ADHD symptoms: A gene-environment correlation study.

BACKGROUND: Chaotic home environments may contribute to children's attention-deficit hyperactivity disorder (ADHD) symptoms. However, ADHD genetic risk may also influence household chaos. This study investigated whether children in chaotic households had more ADHD symptoms, if mothers and children with higher ADHD genetic risk lived in more chaotic households, and the joint association of genetic risk and household chaos on the longitudinal course of ADHD symptoms across childhood. METHODS: Participants were mothers and children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a UK population-representative birth cohort of 2,232 twins. Children's ADHD symptoms were assessed at ages 5, 7, 10 and 12 years. Household chaos was rated by research workers at ages 7, 10 and 12, and by mother's and twin's self-report at age 12. Genome-wide ADHD polygenic risk scores (PRS) were calculated for mothers (n = 880) and twins (n = 1,999); of these, n = 871 mothers and n = 1,925 children had information on children's ADHD and household chaos. RESULTS: Children in more chaotic households had higher ADHD symptoms. Mothers and children with higher ADHD PRS lived in more chaotic households. Children's ADHD PRS was associated with household chaos over and above mother's PRS, suggesting evocative gene-environment correlation. Children in more chaotic households had higher baseline ADHD symptoms and a slower rate of decline in symptoms. However, sensitivity analyses estimated that gene-environment correlation accounted for a large proportion of the association of household chaos on ADHD symptoms. CONCLUSIONS: Children's ADHD genetic risk was independently associated with higher levels of household chaos, emphasising the active role of children in shaping their home environment. Our findings suggest that household chaos partly reflects children's genetic risk for ADHD, calling into question whether household chaos directly influences children's core ADHD symptoms. Our findings highlight the importance of considering parent and child genetic risk in relation to apparent environmental exposures.

A longitudinal twin study of victimization and loneliness from childhood to young adulthood.

The present study used a longitudinal and discordant twin design to explore in depth the developmental associations between victimization and loneliness from mid-childhood to young adulthood. The data were drawn from the Environmental Risk (E-Risk) Longitudinal Twin Study, a birth cohort of 2,232 individuals born in England and Wales during 1994-1995. Diverse forms of victimization were considered, differing across context, perpetrator, and timing of exposure. The results indicated that exposure to different forms of victimization was associated with loneliness in a dose-response manner. In childhood, bullying victimization was uniquely associated with loneliness, over and above concurrent psychopathology, social isolation, and genetic risk. Moreover, childhood bullying victimization continued to predict loneliness in young adulthood, even in the absence of ongoing victimization. Within-twin pair analyses further indicated that this longitudinal association was explained by genetic confounds. In adolescence, varied forms of victimization were correlated with young adult loneliness, with maltreatment, neglect, and cybervictimization remaining robust to controls for genetic confounds. These findings indicate that vulnerability to loneliness in victimized young people varies according to the specific form of victimization in question, and also to the developmental period in which it was experienced.

Externalizing the threat from within: A new direction for researching associations between suicide and psychotic experiences.

A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal behavior [SIB]) in order to optimize survival; however, it must first be demonstrated that such internal threat can both precede and inform PEs. The current study conducted the first known bidirectional analysis of SIB and PEs to test whether SIB could be considered as a plausible antecedent for PEs. Prospective data were utilized from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins, that captured SIB (any self-harm or suicidal attempt) and PEs at ages 12 and 18 years. Cross-lagged panel models demonstrated that the association between SIB at age 12 and PEs at age 18 was as strong as the association between PEs at age 12 and SIB at age 18. Indeed, the best representation of the data was a model where these paths were constrained to be equal (OR = 2.48, 95% CI = 1.63-3.79). Clinical interview case notes for those who reported both SIB and PEs at age 18, revealed that PEs were explicitly characterized by SIB/threat/death-related content for 39% of cases. These findings justify further investigation of the suicidal drive hypothesis.

Measuring early life adversity: A dimensional approach.

Exposure to adversity in childhood is associated with elevations in numerous physical and mental health outcomes across the life course. The biological embedding of early experience during periods of developmental plasticity is one pathway that contributes to these associations. Dimensional models specify mechanistic pathways linking different dimensions of adversity to health and well-being outcomes later in life. While findings from existing studies testing these dimensions have provided promising preliminary support for these models, less agreement exists about how to measure the experiences that comprise each dimension. Here, we review existing approaches to measuring two dimensions of adversity: threat and deprivation. We recommend specific measures for measuring these constructs and, when possible, document when the same measure can be used by different reporters and across the lifespan to maximize the utility with which these recommendations can be applied. Through this approach, we hope to stimulate progress in understanding how particular dimensions of early environmental experience contribute to lifelong health.

Unravelling the contribution of complex trauma to psychopathology and cognitive deficits: a cohort study.

Background: Complex traumas are traumatic experiences that involve multiple interpersonal threats during childhood or adolescence, such as repeated abuse. Complex traumas are hypothesized to lead to more severe psychopathology and poorer cognitive function than other non-complex traumas. However, empirical testing of this hypothesis has been limited to clinical/convenience samples and cross-sectional designs. Aims: To investigate psychopathology and cognitive function in young people exposed to complex, non-complex, or no trauma from a population-representative longitudinal cohort, and to consider the role of pre-existing vulnerabilities. Method: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a population-representative birth-cohort of 2,232 British children. At age 18 years (93% participation), we assessed lifetime exposure to complex and non-complex trauma, past-year psychopathology, and current cognitive function. We also prospectively assessed early childhood vulnerabilities: internalizing and externalizing symptoms at age 5, IQ at age 5, family history of mental illness, family socioeconomic status, and sex. Results: Participants exposed to complex trauma had more severe psychopathology and poorer cognitive function at age 18 compared to both trauma-unexposed participants and those exposed to non-complex trauma. Early childhood vulnerabilities predicted risk of later complex trauma exposure, and largely explained associations of complex trauma with cognitive deficits, but not with psychopathology. Conclusions: By conflating complex and non-complex traumas, current research and clinical practice under-estimate the severity of psychopathology, cognitive deficits, and pre-existing vulnerabilities linked with complex trauma. A better understanding of the mental health needs of people exposed to complex trauma could inform the development of new effective interventions.

The long shadow of childhood trauma for depression in midlife: examining daily psychological stress processes as a persistent risk pathway.

BACKGROUND: Childhood trauma (CT) increases the risk of adult depression. Buffering effects require an understanding of the underlying persistent risk pathways. This study examined whether daily psychological stress processes - how an individual interprets and affectively responds to minor everyday events - mediate the effect of CT on adult depressive symptoms. METHODS: Middle-aged women (N = 183) reported CT at baseline and completed daily diaries of threat appraisals and negative evening affect for 7 days at baseline, 9, and 18 months. Depressive symptoms were measured across the 1.5-year period. Mediation was examined using multilevel structural equation modeling. RESULTS: Reported CT predicted greater depressive symptoms over the 1.5-year time period (estimate = 0.27, s.e. = 0.07, 95% CI 0.15-0.38, p < 0.001). Daily threat appraisals and negative affect mediated the effect of reported CT on depressive symptoms (estimate = 0.34, s.e. = 0.08, 95% CI 0.22-0.46, p < 0.001). Daily threat appraisals explained more than half of this effect (estimate = 0.19, s.e. = 0.07, 95% CI 0.08-0.30, p = 0.004). Post hoc analyses in individuals who reported at least moderate severity of CT showed that lower threat appraisals buffered depressive symptoms. A similar pattern was found in individuals who reported no/low severity of CT. CONCLUSIONS: A reported history of CT acts as a latent vulnerability, exaggerating threat appraisals of everyday events, which trigger greater negative evening affect - processes that have important mental health consequences and may provide malleable intervention targets.

Associations between childhood victimization, inflammatory biomarkers and psychotic phenomena in adolescence: A longitudinal cohort study.

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR = 3.34, 95% CI 1.69-6.59, p = 0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR = 1.94, 95% CI 0.94-4.04, p = 0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p's greater than 0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors.