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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).

Background: Schizophrenia is a neurodevelopmental disorder, and risk genes are thought to act through disruption of brain development. Several genetic studies have identified dystrobrevin-binding protein 1 (DTNBP1, also known as dysbindin) as a potential susceptibility gene for schizophrenia, but its impact on brain development is poorly understood. The present investigation examined for the first time the effects of DTNBP1 on brain structure in children. Our hypothesis was that a genetic variation in DTNBP1 (i.e., the single nucleotide polymorphism rs2619538) would be associated with differences in both gray and white matter brain regions previously implicated in schizophrenia. Methods: Magnetic resonance imaging and voxel-based morphometry were used to examine brain structure in 52 male children aged between 10 and 12 years. Statistical inferences on the effects of DTNBP1 genotype on gray and white matter volume (GMV and WMV) were made at p less than 0.05 after family-wise error correction for multiple comparisons across the whole brain. Results: Individuals homozygous for the schizophrenia high-risk allele (AA) compared with those homozygous for the low-risk allele (TT) expressed reduced GMV in the left anterior cingulate gyrus and reduced WMV in the left medial frontal area. Conclusions: Our results suggest that genetic variation in DTNBP1 is associated with differences in gray and white matter; and that these effects are already evident in children as young as 10-12 years. These findings are consistent with the notion that the DTNBP1 genotype influences brain development and may thereby modulate vulnerability to schizophrenia.

Objective: To investigate the longitudinal development of callous-unemotional traits (CU) in middle childhood using developmental trajectory analyses in a large twin dataset and examine the degree to which genetic and environmental influences contributed to the CU trajectory-group membership in children. Method: The study included 9,462 youths from the Twins Early Development Study, a population-based sample of twins from the United Kingdom. Developmental trajectories were described using teachers' ratings of CU at 7, 9, and 12 years old. Results: We identified four trajectories of CU through general growth mixture modeling: stable high, increasing, decreasing, and stable low. In most cases, the trajectory-group membership was largely driven by genetic and to a lesser extent by nonshared environmental influences for boys and girls. The most notable exception was a strong contribution of shared environment for the girls in the stable-high trajectory group. Conclusions: Our findings suggest distinct developmental trajectories of CU from childhood to early adolescence, which are in most cases influenced by genetic factors and, to a lesser degree, by nonshared environmental factors. Highest heritability was observed for boys on a stable-high CU trajectory. Interestingly, the trajectory-group membership for girls on a stable-high CU trajectory appeared to be almost entirely driven by shared environmental influences. These differences in the etiology of stable-high CU in boys and girls have potential implications for clinical practice and studies attempting to identify genetic and environmental risk factors for high CU. (Contains 1 figure and 4 tables.)

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. [ABSTRACT FROM AUTHOR]

A series of neuroimaging studies have reported structural differences in several subcortical and frontal systems in individuals with stable antisocial behavior (sASB). Specifically, differences have been observed in the prefrontal and temporal cortices (e.g., amygdala and hippocampus). However, the sASB population is typically characterized by co-occurring hyperactivity- inattention symptoms and low cognitive ability. These nuisance variables are likely to complicate the interpretation of findings regarding structural differences associated with sASB. The way in which each study deals with these variables influences the conclusions that can be drawn about the brain structure and function of children and adults with sASB. This article briefly reviews the extant literature in this field before considering two approaches that may be used to deal with comorbidities conceptualized as nuisance variables--namely, the analysis of covariance (ANCOVA) and the matched-group design. Then, the authors illustrate, with their own data, checks that may be performed to ensure the validity of results using ANCOVA. [ABSTRACT FROM AUTHOR]

Callous-unemotional (CU) traits are associated with antisocial and delinquent behaviors in children and represent a potential risk factor for adult psychopathy. However, there is a paucity of longitudinal research that explores the development of these traits, their longitudinal association with conduct problems (CP), and their psychosocial predictors and outcomes. Using a large sample of children followed longitudinally from the Twins Early Development Study (N = 9,578), we described the joint developmental trajectories of CU traits and CP during childhood (between ages 7 and 12) and examined the child- and family-level predictors (4 years old) and concomitant outcomes (12 years old) associated with the trajectories. The developmental trajectories were characterized with teachers' ratings of CU traits and CP from ages 7 to 12. Using general growth mixture modeling, we identified four trajectories of CU traits (stable high, increasing, decreasing, and stable low) and two trajectories of CP (high and low). Compared with the children who followed a low trajectory of CU traits and CP, those who followed a high trajectory of CU traits and CP had more negative child- and family-level predictors at 4 years (including CP, hyperactivity, negative parental discipline, and chaos in the home). Children with high or increasing levels of CU traits and concomitant high levels of CP presented the most negative outcomes at 12 years (including hyperactivity, peer problems, emotional problems, and negative parental feelings). Children with high CU traits and concomitant high levels of CP in childhood should be prioritized for targeted intervention. [ABSTRACT FROM AUTHOR]