A systematic review of childhood maltreatment and resting state functional connectivity

Resting-state functional connectivity (rsFC) has the potential to shed light on how childhood abuse and neglect relates to negative psychiatric outcomes. However, a comprehensive review of the impact of childhood maltreatment on the brain's resting state functional organization has not yet been undertaken. We systematically searched rsFC studies in children and youth exposed to maltreatment. Nineteen studies (total n = 3079) met our inclusion criteria. Two consistent findings were observed. Childhood maltreatment was linked to reduced connectivity between the anterior insula and dorsal anterior cingulate cortex, and with widespread heightened amygdala connectivity with key structures in the salience, default mode, and prefrontal regulatory networks. Other brain regions showing altered connectivity included the ventral anterior cingulate cortex, dorsolateral prefrontal cortex, and hippocampus. These patterns of altered functional connectivity associated with maltreatment exposure were independent of symptoms, yet comparable to those seen in individuals with overt clinical disorder. Summative findings indicate that rsFC alterations associated with maltreatment experience are related to poor cognitive and social functioning and are prognostic of future symptoms. In conclusion, maltreatment is associated with altered rsFC in emotional reactivity, regulation, learning, and salience detection brain circuits. This indicates patterns of recalibration of putative mechanisms implicated in maladaptive developmental outcomes

Epigenetic signatures of childhood abuse and neglect:Implications for psychiatric vulnerability

Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up. Our analyses aimed to identify methylomic variation associated with exposure to five major types of childhood maltreatment. We found that: (i) maltreatment types differ in the extent to which they associate with methylomic variation, with physical exposures showing the strongest associations; (ii) many of the identified loci are annotated to genes previously implicated in stress-related outcomes, including psychiatric and physical disorders (e.g. GABBR1, GRIN2D, CACNA2D4, PSEN2); and (iii) based on gene ontology analyses, maltreatment types not only show unique methylation patterns enriched for specific biological processes (e.g. physical abuse and cardiovascular function), but also share a ‘common’ epigenetic signature enriched for biological processes related to neural development and organismal growth. A stringent set of sensitivity analyses were also run to identify high-confidence associations. Together, findings lend novel insights into epigenetic signatures of childhood abuse and neglect, point to novel potential biomarkers for future investigation and support a molecular link between maltreatment and poor health outcomes. Nevertheless, it will be important in future to replicate findings, as the use of cross-sectional data and high rates of polyvictimization in our study make it difficult to fully disentangle the shared vs unique epigenetic signatures of maltreatment types. Furthermore, studies will be needed to test the role of potential moderators in the identified associations, including age of onset and chronicity of maltreatment exposure. <br/

Modulation of amygdala response to task-irrelevant emotion

It has been shown that as cognitive demands of a non-emotional task increase, amygdala response to task-irrelevant emotional stimuli is reduced. However, it remains unclear whether effects are due to altered task demands, or altered perceptual input associated with task demands. Here, we present fMRI data from 20 adult males during a novel cognitive conflict task in which the requirement to scan emotional information was necessary for task performance and held constant across levels of cognitive conflict. Response to fearful facial expressions was attenuated under high (vs low) conflict conditions, as indexed by both slower reaction times and reduced right amygdala response. Psychophysiological interaction analysis showed that increased amygdala response to fear in the low conflict condition was accompanied by increased functional coupling with middle frontal gyrus, a prefrontal region previously associated with emotion regulation during cognitive task performance. These data suggest that amygdala response to emotion is modulated as a function of task demands, even when perceptual inputs are closely matched across load conditions. PPI data also show that, in particular emotional contexts, increased functional coupling of amygdala with prefrontal cortex can paradoxically occur when executive demands are lower

Social information use in adolescents with conduct problems and varying levels of callous‐unemotional traits

BACKGROUND: Adolescents with conduct problems (CP) are characterised by difficulties with social relationships and display atypical social cognition, such as when interpreting emotional expressions or engaging in social problem-solving. One important aspect of social cognition that warrants investigation is the degree to which these adolescents factor others' views into their already held beliefs, and strategies used to do so. Effective social information use enables attunement to social environment, cooperation, and social problem-solving. Difficulties in this regard could contribute to problems in social interactions in adolescents with CP, and may vary with adolescents' high (CP/HCU) versus low levels of callous-unemotional traits (CP/LCU). METHODS: We compared social information use in boys (11–16 years) with CP/HCU (n = 32), CP/LCU (n = 31) and typically developing (TD) peers (n = 45), matched for IQ. Participants provided estimates of numbers of animals on a screen, saw another adolescent's estimate, and could adjust their initial estimate. We compared two aspects of social information use: (1) degree of adjustment of initial estimate towards another's estimate and (2) strategy use when adjusting estimates. RESULTS: Degree of adjustment towards another's estimate did not vary across groups, but strategy use did. Adolescents with CP/LCU compromised less following social information than TD peers. CONCLUSIONS: Findings suggest that while adolescents with CP are able to take social information into account, those with CP/LCU use this information in a way that differs from other groups and could be less efficient. This warrants further systematic investigation as it could represent a target for behaviour management strategies. Overall, this study highlights the need for more research delineating the social-cognitive profile of adolescents with CP/LCU

Neural processing associated with cognitive and affective Theory of Mind in adolescents and adults

Theory of Mind (ToM) is the ability to attribute thoughts, intentions and beliefs to others. This involves component processes, including cognitive perspective taking (cognitive ToM) and understanding emotions (affective ToM). This study assessed the distinction and overlap of neural processes involved in these respective components, and also investigated their development between adolescence and adulthood. While data suggest that ToM develops between adolescence and adulthood, these populations have not been compared on cognitive and affective ToM domains. Using fMRI with 15 adolescent (aged 11–16 years) and 15 adult (aged 24–40 years) males, we assessed neural responses during cartoon vignettes requiring cognitive ToM, affective ToM or physical causality comprehension (control). An additional aim was to explore relationships between fMRI data and self-reported empathy. Both cognitive and affective ToM conditions were associated with neural responses in the classic ToM network across both groups, although only affective ToM recruited medial/ventromedial PFC (mPFC/vmPFC). Adolescents add- itionally activated vmPFC more than did adults during affective ToM. The specificity of the mPFC/vmPFC response during affective ToM supports evidence from lesion studies suggesting that vmPFC may integrate affective information during ToM. Furthermore, the differential neural response in vmPFC between adult and adolescent groups indicates developmental changes in affective ToM processing

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

Association of callous traits with reduced neural response to others’ pain in children with conduct problems

Children with conduct problems (CP) persistently violate others’ rights and represent a considerable societal cost [1]. These children also display atypical empathic responses to others’ distress [2], which may partly account for their violent and antisocial behavior. Callous traits index lack of empathy in these children and confer risk for adult psychopathy [3]. Investigating neural responses to others’ pain is an ecologically valid method to probe empathic processing [4], but studies in children with CP have been inconclusive [5, 6]. Using functional magnetic resonance imaging (fMRI), we measured neural responses to pictures of others in pain (versus no pain) in a large sample of children with CP and matched controls. Relative to controls, children with CP showed reduced blood oxygen level-dependent responses to others’ pain in bilateral anterior insula (AI), anterior cingulate cortex (ACC), and inferior frontal gyrus, regions associated with empathy for pain in previous studies [7, 8]. In the CP group, callous traits were negatively associated with responses to others’ pain in AI and ACC. We conclude that children with CP have atypical neural responses to others’ pain. The negative association between callous traits and AI/ACC response could reflect an early neurobiological marker indexing risk for empathic deficits seen in adult psychopathy

Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment : neural markers of vulnerability?

Childhood maltreatment has been shown to significantly elevate the risk of psychiatric disorder. Previous neuroimaging studies of children exposed to maltreatment have reported atypical neural structure in several regions, including the prefrontal cortex and temporal lobes. These studies have exclusively investigated volumetric differences rather than focusing on genetically and developmentally distinct indices of brain structure

Disentangling the mental health impact of child abuse and neglect

It is unclear whether maltreatment types exert common or specific effects on mental health. In the current study, we aimed to systematically characterize the unique, shared and cumulative effects of maltreatment types on psychiatric symptoms, using data drawn from a community sample of high-risk youth (n = 204, M = 18.85). Analyses controlled for a range of potentially confounding variables, including socio-demographic variables, neighbourhood deprivation and levels of community violence exposure. Outcome measures included multi-informant reports of internalizing difficulties, as well as data on externalizing problems and trauma-related symptoms. We found that (i) consistent with previous studies, maltreatment types were highly interrelated and frequently co-occurred; (ii) symptom severity linearly increased with the number of maltreatment types experienced (more so for self-report vs informant ratings); and (iii) while most forms of maltreatment were significantly associated with mental health outcomes when examined individually, few unique effects were observed when modelling maltreatment types simultaneously, pointing to an important role of shared variance in driving maltreatment effects on mental health. Emotional abuse emerged as the main independent predictor of psychiatric symptomatology – over and above other maltreatment types – and this effect was comparable for males and females (i.e. no significant interaction with sex). Findings contribute to a better understanding of heterogeneity in individual responses to maltreatment