Functional brain plasticity following childhood maltreatment: A longitudinal fMRI investigation of autobiographical memory processing.

Altered autobiographical memory (ABM) processing characterizes some individuals with experiences of childhood maltreatment. This fMRI study of ABM processing evaluated potential developmental plasticity in neural functioning following maltreatment. Adolescents with (N = 19; MT group) and without (N = 18; Non-MT group) documented childhood maltreatment recalled specific ABMs in response to emotionally valenced cue words during fMRI at baseline (age 12.71 ± 1.48) and follow-up (14.88 ± 1.53 years). Psychological assessments were collected at both timepoints. Longitudinal analyses were carried out with BOLD signal changes during ABM recall and psychopathology to investigate change over time. In both groups there was relative stability of the ABM brain network, with some developmental maturational changes observed in cortical midline structures (ventromedial PFC (vmPFC), posterior cingulate cortex (pCC), and retrosplenial cortex (rSC). Significantly increased activation of the right rSC was observed only in the MT group, which was associated with improved psychological functioning. Baseline group differences in relation to hippocampal functioning, were not detected at follow-up. This study provides preliminary empirical evidence of functional developmental plasticity in children with documented maltreatment experience using fMRI. This suggests that altered patterns of brain function, associated with maltreatment experience, are not fixed and may reflect the potential to track a neural basis of resilience.

Understanding the development of psychopathy: progress and challenges.

Psychopathy is an adult condition that incurs substantial societal and individual costs. Here we review neurocognitive and genetically informative studies that shed light on how and why this condition emerges. Children cannot present with psychopathy. However, the presence of callous-unemotional (CU) traits can distinguish a group of children who are at elevated risk of psychopathy in adulthood. These children display diminished empathy and guilt and show attenuated brain activation to distress cues in others. Genetically informative studies indicate that individual differences in CU traits show moderate-to-strong heritability, but that protective environmental factors can counter heritable risk. On the basis of the extant research findings, we speculate on what might represent the priorities for research over the next decade. We also consider the clinical implications of these research findings. In particular, we consider the importance of delineating what precisely works for children with CU traits (and their parents) and the ways in which intervention and prevention programs may be optimized to improve engagement as well as clinical outcomes.

Neural responses to fearful eyes in children with conduct problems and varying levels of callous-unemotional traits.

BACKGROUND: Children with conduct problems (CP) are a heterogeneous group. Those with high levels of callous-unemotional traits (CP/HCU) appear emotionally under-reactive at behavioural and neural levels whereas those with low levels of CU traits (CP/LCU) appear emotionally over-reactive, compared with typically developing (TD) controls. Investigating the degree to which these patterns of emotional reactivity are malleable may have important translational implications. Instructing participants with CP/HCU to focus on the eyes of fearful faces (i.e. the most salient feature) can ameliorate their fear-recognition deficits, but it is unknown whether this is mediated by amygdala response. It is also unknown whether focusing on fearful eyes is associated with increased amygdala reactivity in CP/LCU. METHOD: Functional magnetic resonance imaging (fMRI) was used to measure neural responses to fearful and calm faces in children with CP/HCU, CP/LCU and TD controls (n = 17 per group). On half of trials participants looked for a blue dot anywhere within target faces; on the other half, participants were directed to focus on the eye region. RESULTS: Reaction time (RT) data showed that CP/LCU were selectively slowed in the fear/eyes condition. For the same condition, CP/LCU also showed increased amygdala and subgenual anterior cingulate cortex (sgACC)/orbitofrontal cortex (OFC) responses compared with TD controls. RT and amygdala response to fear/eyes were correlated in CP/LCU only. No effects of focusing on the eye region were observed in CP/HCU. CONCLUSIONS: These data extend the evidence base suggesting that CU traits index meaningful heterogeneity in conduct problems. Focusing on regulating reactive emotional responses may be a fruitful strategy for children with CP/LCU.

DNA methylation and substance-use risk: a prospective, genome-wide study spanning gestation to adolescence.

Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14-18). We found that, at birth, epigenetic variation across a tightly interconnected genetic network (n=65 loci; q<0.05) associated with greater levels of substance use during adolescence, as well as an earlier age of onset amongst users. Associations were specific to the neonatal period and not observed at age 7. Key annotated genes included PACSIN1, NEUROD4 and NTRK2, implicated in neurodevelopmental processes. Several of the identified loci were associated with known methylation quantitative trait loci, and consequently likely to be under significant genetic control. Collectively, these 65 loci were also found to partially mediate the effect of prenatal maternal tobacco smoking on adolescent substance use. Together, findings lend novel insights into epigenetic correlates of substance use, highlight birth as a potentially sensitive window of biological vulnerability and provide preliminary evidence of an indirect epigenetic pathway linking prenatal tobacco exposure and adolescent substance use.

Understanding Addiction as a Developmental Disorder: An Argument for a Developmentally Informed Multilevel Approach.

Substance abuse and drug addiction are two of the most common psychopathologies among the general population. While a host of risk factors are associated with the onset of drug abuse and drug addiction, there is a growing body of evidence pointing to the powerful influence of early adverse experiences, both child neglect and maltreatment, as well as drug use and abuse in parents and/or primary caretakers. We consider the case for drug addiction as a developmental disorder, outlining the need to consider the role of genetic, epigenetic, and neurobiological factors alongside experiences of adversity at key stages of development. Such a multilevel approach within a developmental framework has the potential to reframe our understanding of how addiction emerges and is maintained, and is essential if we are to identify the mechanisms underlying this disorder to better inform effective treatment and prevention across the generations.