Shedding Light on Antisocial Behavior Through Genetically Informed Research.

Antisocial behavior (ASB) refers to a set of behaviors that violate social norms and disregard the well-being and rights of others. In this review, we synthesize evidence from studies using genetically informed designs to investigate the genetic and environmental contributions to individual differences in ASB. We review evidence from studies using family data (twin and adoption studies) and measured DNA (candidate gene and genome-wide association studies) that have informed our understanding of ASB. We describe how genetically informative designs are especially suited to investigate the nature of environmental risk and the forms of gene-environment interplay. We also highlight clinical and legal implications, including how insights from genetically informed research can help inform prevention and intervention, and we discuss some challenges and opportunities within this field of research.

Genetic algorithms reveal profound individual differences in emotion recognition.

Emotional communication relies on a mutual understanding, between expresser and viewer, of facial configurations that broadcast specific emotions. However, we do not know whether people share a common understanding of how emotional states map onto facial expressions. This is because expressions exist in a high-dimensional space too large to explore in conventional experimental paradigms. Here, we address this by adapting genetic algorithms and combining them with photorealistic three-dimensional avatars to efficiently explore the high-dimensional expression space. A total of 336 people used these tools to generate facial expressions that represent happiness, fear, sadness, and anger. We found substantial variability in the expressions generated via our procedure, suggesting that different people associate different facial expressions to the same emotional state. We then examined whether variability in the facial expressions created could account for differences in performance on standard emotion recognition tasks by asking people to categorize different test expressions. We found that emotion categorization performance was explained by the extent to which test expressions matched the expressions generated by each individual. Our findings reveal the breadth of variability in people's representations of facial emotions, even among typical adult populations. This has profound implications for the interpretation of responses to emotional stimuli, which may reflect individual differences in the emotional category people attribute to a particular facial expression, rather than differences in the brain mechanisms that produce emotional responses.

Reviewing explore/exploit decision-making as a transdiagnostic target for psychosis, depression, and anxiety.

In many everyday decisions, individuals choose between trialling something novel or something they know well. Deciding when to try a new option or stick with an option that is already known to you, known as the "explore/exploit" dilemma, is an important feature of cognition that characterises a range of decision-making contexts encountered by humans. Recent evidence has suggested preferences in explore/exploit biases are associated with psychopathology, although this has typically been examined within individual disorders. The current review examined whether explore/exploit decision-making represents a promising transdiagnostic target for psychosis, depression, and anxiety. A systematic search of academic databases was conducted, yielding a total of 29 studies. Studies examining psychosis were mostly consistent in showing that individuals with psychosis explored more compared with individuals without psychosis. The literature on anxiety and depression was more heterogenous; some studies found that anxiety and depression were associated with more exploration, whereas other studies demonstrated reduced exploration in anxiety and depression. However, examining a subset of studies that employed case-control methods, there was some evidence that both anxiety and depression also were associated with increased exploration. Due to the heterogeneity across the literature, we suggest that there is insufficient evidence to conclude whether explore/exploit decision-making is a transdiagnostic target for psychosis, depression, and anxiety. However, alongside our advisory groups of lived experience advisors, we suggest that this context of decision-making is a promising candidate that merits further investigation using well-powered, longitudinal designs. Such work also should examine whether biases in explore/exploit choices are amenable to intervention.

Evaluating the sensitivity to threat and affiliative reward (STAR) model in relation to the development of conduct problems and callous-unemotional traits across early adolescence.

BACKGROUND: The Sensitivity to Threat and Affiliative Reward (STAR) model proposes low threat sensitivity and low affiliation as risk factors for callous-unemotional (CU) traits. Preliminary evidence for the STAR model comes from work in early childhood. However, studies are needed that explore the STAR dimensions in late childhood and adolescence when severe conduct problems (CP) emerge. Moreover, it is unclear how variability across the full spectrum of threat sensitivity and affiliation gives rise to different forms of psychopathology beyond CU traits. METHODS: The current study addressed these gaps using parent- and child-reported data from three waves and a sub-study of the Adolescent Brain Cognitive Development Study® of 11,878 youth (48% female; ages 9-12). RESULTS: Consistent with the STAR model, low threat sensitivity and low affiliation were independently related to CU traits across informants and time. Moreover, there was significant interaction between the STAR dimensions, such that children with lower sensitivity to threat and lower affiliation had higher parent-reported CU traits. Unlike CU traits, children with higher threat sensitivity had higher parent-reported CP and anxiety. Finally, children with lower affiliation had higher parent-reported CP, anxiety, and depression. Results largely replicated across informants and time, and sensitivity analysis revealed similar findings in children with and without DSM-5 defined CP. CONCLUSIONS: Results support the STAR model hypotheses as they pertain to CU traits and delineate threat sensitivity and affiliation as independent transdiagnostic risk factors for different types of psychopathology. Future research is needed to develop fuller and more reliable and valid measures of affiliation and threat sensitivity across multiple assessment modalities.

Reduced prosocial motivation and effort in adolescents with conduct problems and callous-unemotional traits.

BACKGROUND: Prosocial behaviours - acts that benefit others - are of crucial importance for many species including humans. However, adolescents with conduct problems (CP), unlike their typically developing (TD) peers, demonstrate markedly reduced engagement in prosocial behaviours. This pattern is particularly pronounced in adolescents with CP and high levels of callous-unemotional traits (CP/HCU) who are at increased risk of developing psychopathy in adulthood. While a substantial amount of research has investigated the cognitive-affective mechanisms thought to underlie antisocial behaviour, much less is known about the mechanisms that could explain reduced prosocial behaviours in adolescents with CP. METHODS: Here we examined the willingness to exert effort to benefit oneself (self) and another person (other, prosocial condition) in children with CP/HCU, CP and lower levels of CU traits (CP/LCU) and their TD peers. The task captured both prosocial choices, and actual effort exerted following prosocial choices, in adolescent boys aged 11-16 (27 CP/HCU; 34 CP/LCU; 33 TD). We used computational modelling to reveal the mechanistic processes involved when choosing prosocial acts. RESULTS: We found that both CP/HCU and CP/LCU groups were more averse to initiating effortful prosocial acts than TD adolescents - both at a cognitive and at a behavioural level. Strikingly, even if they chose to initiate a prosocial act, the CP/HCU group exerted less effort following this prosocial choice than other groups. CONCLUSIONS: Our findings indicate that reduced exertion of effort to benefit others may be an important factor that differentiates adolescents with CP/HCU from their peers with CP/LCU. They offer new insights into what might drive low prosocial behaviour in adolescents with CP, including vulnerabilities that may particularly characterise those with high levels of CU traits.

Explaining the influence of non-shared environment (NSE) on symptoms of behaviour problems from preschool to adulthood: mind the missing NSE gap.

BACKGROUND: Individual differences in symptoms of behaviour problems in childhood and adolescence are not primarily due to nature or nurture - another substantial source of variance is non-shared environment (NSE). However, few specific environmental factors have been found to account for these NSE estimates. This creates a 'missing NSE' gap analogous to the 'missing heritability' gap, which refers to the shortfall in identifying DNA differences responsible for heritability. We assessed the extent to which variance in behaviour problem symptoms during the first two decades of life can be accounted for by measured NSE effects after controlling for genetics and shared environment. METHODS: The sample included 4,039 pairs of twins in the Twins Early Development Study whose environments and symptoms of behaviour problems were assessed in preschool, childhood, adolescence and early adulthood via parent, teacher and self-reports. Twin-specific environments were assessed via parent-reports, including early life adversity, parental feelings, parental discipline and classroom environment. Multivariate longitudinal twin model-fitting was employed to estimate the variance in behaviour problem symptoms at each age that could be predicted by environmental measures at the previous age. RESULTS: On average across childhood, adolescence and adulthood, parent-rated NSE composite measures accounted for 3.4% of the reliable NSE variance (1.0% of the total variance) in parent-rated, symptoms of behaviour problems, 0.5% (0.1%) in teacher-rated symptoms and 0.9% (0.5%) in self-rated symptoms after controlling for genetics, shared environment and error of measurement. Cumulatively across development, our parent-rated NSE measures in preschool, childhood and adolescence predicted 4.7% of the NSE variance (2.0% of the total variance) in parent-rated and 0.3% (0.2%) in self-rated behaviour problem symptoms in adulthood. CONCLUSIONS: The missing NSE gap between variance explained by measured environments and total NSE variance is large. Home and classroom environments are more likely to influence behaviour problem symptoms via genetics than via NSE.

Parenting boys with conduct problems and callous-unemotional traits: parent and child perspectives.

Parenting children with conduct problems (CP) is challenging, yet very little research has examined parenting using both quantitative and qualitative methods, from the perspective of the child and their parent/caregiver, and separately for those with high vs. low levels of callous-unemotional traits (HCU vs. LCU). One hundred and forty-six boys aged 11-16 [Typically developing (TD) n = 31; CP/HCU n = 35; CP/LCU n = 35] and their parents/caregivers completed the Alabama Parenting Questionnaire and provided a written qualitative statement describing their respective experiences of parenting/being parented. Parents/caregivers of CP/HCU boys reported more difficulty with child monitoring and supervision than parents of TD boys. This was echoed in qualitative reports of parents of CP/HCU boys reporting concerns regarding their child's safety. Parents/caregivers of both groups of CP boys reported more inconsistent discipline than parents of TD boys. Parental qualitative descriptions of challenging behavior in CP/HCU boys, and difficulties with setting boundaries and motivating CP/LCU boys, provided further insight to the potential triggers for inconsistent discipline. Qualitative reports from boys with CP indicated that they understood the parenting challenges their parents/caregivers faced. These findings replicate and extend previous work on the associations between parenting and CP. Children with CP/HCU and CP/LCU show some commonalities and differences in their parenting experiences and CP children and their parents/caregivers do not necessarily share all the same perceptions or concerns. CP interventions often involve parent/family engagement and this research highlights the continued importance of examining both parent and child perspectives.

The providential randomisation of genotypes.

When building causal knowledge in behavioural genetics, the natural randomisation of genotypes at conception (approximately analogous to the artificial randomisation occurring in randomised controlled trials) facilitates the discovery of genetic causes. More importantly, the randomisation of genetic material within families also enables a better identification of (environmental) risk factors and aetiological pathways to diseases and behaviours.

Commentary: Will genomics revolutionise research on gene-environment interplay?

The synthesis of quantitative genetics and molecular genetics is transforming research in the behavioural sciences. The ability to measure inherited DNA differences directly has led to polygenic scores and to new methods to estimate heritability and genetic correlations. This issue provides examples of how these advances can be appllied to research on gene-environment interplay in developmental psychopathology.

Trust and childhood maltreatment: evidence of bias in appraisal of unfamiliar faces.

BACKGROUND: Child maltreatment is associated with poorer social functioning and increased risk of mental health problems in adolescence and adulthood, but the processes underlying these associations remain unclear. Although crucial for establishing and maintaining relationships, trust judgements have not been experimentally investigated in children who have experienced abuse and neglect. METHODS: A community-based sample of 75 children aged 8-16 years with maltreatment documented on the basis of social services records, and a group of 70 peers matched on age, gender, cognitive ability, socioeconomic status, and ethnicity took part in the study. Children completed a trustworthiness face-judgement task in which they appraised the trustworthiness of unfamiliar facial stimuli varying along a computationally modelled trustworthiness dimension. RESULTS: In line with clinical observations that childhood maltreatment is associated with an atypical pattern of trust processing, children with maltreatment experience were significantly less likely than their peers to rate unfamiliar faces as trustworthy. Moreover, they were more variable in their trust attributions than their peers. CONCLUSIONS: The study provides compelling experimental evidence that children with documented maltreatment perceive others as less trustworthy than their peers and are less consistent in their estimates of trustworthiness in others. Over time, alterations in trust processing may disrupt the development of social bonds and contribute to 'social thinning' (a reduction in the extent and quality of social relationships), leaving children more vulnerable to environmental stressors, increasing risk of mental health difficulties.

Using DNA to predict behaviour problems from preschool to adulthood.

BACKGROUND: One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems. METHOD: Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems, and peer problems as rated by parents, teachers, and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalising, and internalising) across ages (from age 2 to 21) and across raters in penalised regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures. RESULTS: Multi-GPS prediction of behaviour problems increased from <2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability, although to a lesser extent, mirrored patterns of multi-GPS prediction as they increased from <40% to 83%. CONCLUSIONS: The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our approach can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater, or GPS.

Individual differences in sensitivity to the early environment as a function of amygdala and hippocampus volumes: An exploratory analysis in 12-year-old boys.

Children differ in their response to environmental exposures, with some being more sensitive to contextual factors than others. According to theory, such variability is the result of individual differences in neurobiological sensitivity to environmental features, with some individuals generally more affected by both negative and/or positive experiences. In this exploratory study we tested whether left and right amygdala and hippocampus volumes (corrected for total brain size) account for individual differences in response to environmental influences in a sample of 62 boys. Cumulative general environmental quality, ranging from low to high, was measured across the first 9 years and child behavior was reported by teachers when boys were 12-13 years old. According to analyses, only the left amygdala volume - not any of the other brain volumes - emerged as an important brain region for sensitivity to positive environmental aspects. Boys with a larger left amygdala benefited significantly more from higher environmental quality than boys with a smaller left amygdala whilst not being more vulnerable to lower quality. Besides providing preliminary evidence for differences in environmental sensitivity due to brain structure, the results also point to the left amygdala as having a specific role regarding the response to environmental influences.

Genetic and environmental influences on the developmental trajectory of callous-unemotional traits from childhood to adolescence.

BACKGROUND: This study examined the genetic and environmental influences underlying baseline level and developmental course of callous-unemotional (CU) traits across childhood and adolescence. METHODS: The data on 8,958 twin pairs (3,108 MZ twin pairs and 5,850 DZ twin pairs) from the Twins Early Development Study were analysed. CU traits were assessed at ages 7, 9, 12 and 16 by mothers and analysed using a biometric latent growth model. RESULTS: Individual differences in the baseline level of CU traits were highly heritable (76.5%), while the heritability of the developmental course of CU traits was moderate (43.6%). The genetic influences on baseline level and developmental course of CU traits were mostly nonoverlapping. Nonshared environment made a modest contribution to the baseline level of CU traits (21.7%). Nonshared environmental influences on the developmental course of CU traits were moderate (43.2%), with nearly half of them being the same as those influencing the baseline level and just over half being specific. Shared environmental effects did not contribute to systematic change across childhood and adolescence but were rather age-specific. CONCLUSIONS: Our findings demonstrate that rather than only being conceptualized as factors of stability, genes also play a dynamic role in explaining systematic change in CU traits. Genetic effects for the initial risk and subsequent development of CU traits are not the same. In addition to genetic factors, nonshared environmental influences play an important role in explaining why some children will increase or maintain their CU traits over time, whereas other will desist. New genetic and environmental influences with age suggest that repeated, age-tailored interventions may be required throughout development to make a lasting difference in the presentation of CU traits and associated outcomes.

Childhood sexual abuse in patients with severe mental Illness: Demographic, clinical and functional correlates.

OBJECTIVE: To use data from electronic health records (EHRs) to describe the demographic, clinical and functional correlates of childhood sexual abuse (CSA) in patients with severe mental illness (SMI), and compare their clinical outcomes (admissions and receipt of antipsychotic medications) to those of patients with no recorded history of CSA. METHODS: We applied a string-matching technique to clinical text records of 7000 patients with SMI (non-organic psychotic disorders or bipolar disorder), identifying 619 (8.8%) patients with a recorded history of CSA. Data were extracted from both free-text and structured fields of patients' EHRs. RESULTS: Comorbid diagnoses of major depressive disorder, post-traumatic stress disorder and personality disorders were more prevalent in patients with CSA. Positive psychotic symptoms, depressed mood, self-harm, substance use and aggression were also more prevalent in this group, as were problems with relationships and living conditions. The odds of inpatient admissions were higher in patients with CSA than in those without (adjusted OR = 1.95, 95% CI: 1.64-2.33), and they were more likely to have spent more than 10 days per year as inpatients (adjusted OR = 1.32, 95% CI: 1.07-1.62). Patients with CSA were more likely to be prescribed antipsychotic medications (adjusted OR = 2.48, 95% CI: 1.69-3.66) and be given over 75% of the maximum recommended daily dose (adjusted OR = 1.72, 95% CI: 1.44-2.04). CONCLUSION: Data-driven approaches are a reliable, promising avenue for research on childhood trauma. Clinicians should be trained and skilled at identifying childhood adversity in patients with SMI, and addressing it as part of the care plan.

The role of mental health symptomology and quality of life in predicting referrals to special child and adolescent mental health services.

BACKGROUND: Children and adolescents' mental health problems have been largely assessed with conventional symptom scales, for example, Strengths and Difficulties Questionnaire (SDQ) given that it is one of the mostly widely used measures in specialist Child and Adolescent Mental Health Services (CAMHS). However, this emphasis on symptom scales might have missed some important features of the mental health challenges that children and young people experience including day to day functioning and life satisfaction aspect (i.e. qualify of life). METHOD: The study examined longitudinal association between a young person's self-perceptions of quality of life and mental health difficulties and referral to specialist CAMHS service using a population cohort study (Targeted Mental Health in Schools service data) nested within a large-scale linkage between school (National Pupil Data base) and child mental health service administrative data (South London and Maudsley NHS Foundation Trust children and adolescent mental health services health records). Cox proportional hazard regression to estimate crude and adjusted hazard ratios (HRs) for the association between participant psychopathology, and incidence of CAMHS referral. RESULTS: Pupils experiencing more behavioural difficulties, had an increased incidence of CAMHS referral (adjusted hazard ratio 1.1, 95% confidence interval 1.0-1.2). However, pupils who reported higher health related quality of life had a lower incidence of CAMHS referral over the follow-up period (adjusted hazard hario 0.94, 95% confidence interval 0.9-0.98). CONCLUSION: Children and young people's perception of their quality of life should be considered at the stages of a clinical needs assessment.

Autobiographical memory as a latent vulnerability mechanism following childhood maltreatment: Association with future depression symptoms and prosocial behavior.

OBJECTIVES: Childhood maltreatment is associated with altered neural reactivity during autobiographical memory (ABM) recall and a pattern of overgeneral memory (OGM). Altered ABM and OGM have been linked with psychopathology and poorer social functioning. The present study investigated the association between altered ABM and subsequent socio-emotional functioning (measured two years later) in a sample of adolescents with (N = 20; maltreatment group, MT) and without (N = 17; non-MT group) documented childhood maltreatment histories. METHOD: At baseline, adolescents (aged 12.6 ± 1.45 years) were administered the Autobiographical Memory Test to measure OGM. Participants also recalled specific ABMs in response to emotionally valenced cue words during functional MRI. Adolescents in both groups underwent assessments measuring depressive symptoms and prosocial behavior at both timepoints. Regression analyses were carried out to predict outcome measures at follow-up controlling for baseline levels. RESULTS: In the MT group, greater OGM at baseline significantly predicted reduced prosocial behavior at follow-up and showed a trend level association with elevated depressive symptoms. Patterns of altered ABM-related brain activity did not significantly predict future psycho-social functioning. CONCLUSIONS: The current findings highlight the potential value of OGM as a cognitive mechanism that could be targeted to reduce risk of depression in adolescents with prior histories of maltreatment.

Association of subcortical gray-matter volumes with life-course-persistent antisocial behavior in a population-representative longitudinal birth cohort.

Neuropsychological evidence supports the developmental taxonomy theory of antisocial behavior, suggesting that abnormal brain development distinguishes life-course-persistent from adolescence-limited antisocial behavior. Recent neuroimaging work confirmed that prospectively-measured life-course-persistent antisocial behavior is associated with differences in cortical brain structure. Whether this extends to subcortical brain structures remains uninvestigated. This study compared subcortical gray-matter volumes between 672 members of the Dunedin Study previously defined as exhibiting life-course-persistent, adolescence-limited or low-level antisocial behavior based on repeated assessments at ages 7-26 years. Gray-matter volumes of 10 subcortical structures were compared across groups. The life-course-persistent group had lower volumes of amygdala, brain stem, cerebellum, hippocampus, pallidum, thalamus, and ventral diencephalon compared to the low-antisocial group. Differences between life-course-persistent and adolescence-limited individuals were comparable in effect size to differences between life-course-persistent and low-antisocial individuals, but were not statistically significant due to less statistical power. Gray-matter volumes in adolescence-limited individuals were near the norm in this population-representative cohort and similar to volumes in low-antisocial individuals. Although this study could not establish causal links between brain volume and antisocial behavior, it constitutes new biological evidence that all people with antisocial behavior are not the same, supporting a need for greater developmental and diagnostic precision in clinical, forensic, and policy-based interventions.

Prevalence of conduct problems and social risk factors in ethnically diverse inner-city schools.

BACKGROUND: In the UK, around 5% of 11-16-year olds experience conduct problems of clinical importance. However, there are limited data on prevalence of conduct problems by ethnic group, and how putative social risk factors may explain any variations in prevalence. This study has two main aims: (1) to estimate the prevalence and nature of conduct problems overall, and by ethnic group and gender, among adolescents in diverse inner-city London schools; (2) to assess the extent to which putative risk factors - racial discrimination, socioeconomic status, parental control, and troublesome friends - explain any observed differences in prevalence of conduct problems between ethnic groups. METHODS: This study uses baseline data from REACH, an accelerated cohort study of adolescent mental health in inner-city London. Self-report questionnaire data were collected on conduct problems and a range of distinct putative social risk factors (including racial discrimination, free school meals, troublesome friends, and parental care and control). A total of 4353 pupils, 51% girls, aged 11-14 participated. We estimated prevalence of conduct problems and used multilevel logistic regression to examine differences by ethnicity and gender and associations with putative risk factors. RESULTS: Prevalence of conduct problems in inner-city schools was around three times higher than reported in national studies (i.e., 16% [95%CI: 15·2-17·5] vs. 5% [95%CI 4·6-5·9]). Compared with overall prevalence, conduct problems were lower among Indian/Pakistani/Bangladeshi (RR: 0.53 [95% CI:0.31-0.87]) and white British (RR: 0.65 [0.51-0.82]) groups, and higher among black Caribbean (RR: 1.39 [95%CI:1.19-1.62]) and mixed white and black (RR: 1.29 [95% CI: 1.02-1.60]) groups. Risk of conduct problems was higher among those who were exposed to racial discrimination compared with those who were not (RR: 1.95 [95% CI: 1.59-2.31]). CONCLUSIONS: Conduct problems are markedly more common in inner-city schools, and variations in the prevalence of conduct problems are, to some extent, rooted in modifiable social contexts and experiences, such as experiences of racial discrimination.

Investigating patterns of neural response associated with childhood abuse v. childhood neglect.

BACKGROUND: Childhood maltreatment is robustly associated with increased risk of poor mental health outcome and changes in brain function. The authors investigated whether childhood experience of abuse (e.g. physical, emotional and sexual abuse) and neglect (physical and emotional deprivation) was differentially associated with neural reactivity to threat. METHODS: Participants were drawn from an existing study and allocated to one of four groups based on self-report of childhood maltreatment experience: individuals with childhood abuse experiences (n = 70); individuals with childhood neglect experiences (n = 87); individuals with combined experience of childhood abuse and neglect (n = 50); and non-maltreated individuals (n = 207) propensity score matched (PSM) on gender, age, IQ, psychopathology and SES. Neural reactivity to facial cues signalling threat was compared across groups, allowing the differential effects associated with particular forms of maltreatment experience to be isolated. RESULTS: Brain imaging analyses indicated that while childhood abuse was associated with heightened localised threat reactivity in ventral amygdala, experiences of neglect were associated with heightened reactivity in a distributed cortical fronto-parietal network supporting complex social and cognitive processing as well as in the dorsal amygdala. Unexpectedly, combined experiences of abuse and neglect were associated with hypo-activation in several higher-order cortical regions as well as the amygdala. CONCLUSIONS: Different forms of childhood maltreatment exert differential effects in neural threat reactivity: while the effects of abuse are more focal, the effects of neglect and combined experiences of abuse are more distributed. These findings are relevant for understanding the range of psychiatric outcomes following childhood maltreatment and have implications for intervention.

Heightened amygdala reactivity and increased stress generation predict internalizing symptoms in adults following childhood maltreatment.

BACKGROUND: Childhood maltreatment is one of the most potent predictors of future psychopathology, including internalizing disorders. It remains unclear whether heightened amygdala reactivity to threat and elevated stress exposure may be implicated in the pathogenesis and maintenance of internalizing disorders among individuals with a history of childhood maltreatment. METHODS: Using data from a sample of 1,144 young adults, we investigated the contribution of baseline threat-related amygdala reactivity and prospective major stressful life events to internalizing symptoms severity 1 year later (on average) in individuals with a history of maltreatment (n = 100) and propensity score matched nonmaltreated peers (n = 96). RESULTS: Even after stringently matching for several potentially confounding variables - including baseline internalizing symptoms, socioeconomic status and IQ - childhood maltreatment status predicted increased amygdala reactivity at baseline, elevated post-baseline exposure to major stressful life events and internalizing symptoms at follow-up. We also showed, for the first time, that amygdala reactivity at baseline and also post-baseline exposure to major stressful life events mediated the association between a history of maltreatment and future internalizing symptoms. CONCLUSIONS: These findings provide support for the view that maltreatment is a potent developmental insult leading to long-lasting neurocognitive recalibrations of the threat processing system. It is possible that such alterations, over time, may impact mental health functioning by compromising the ability to effectively negotiate everyday challenges (stress susceptibility). These alterations were not, however, found to sensitize an individual to the impact of major stressful life events. The results of this study also lend compelling support to the view that increased psychiatric risk, in the context of childhood maltreatment, follows from an increased propensity to experience major stressful life events (stress generation).