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.

Regulatory focus theory (RFT) postulates two cognitive-motivational systems for personal goal pursuit: the promotion system, which is associated with ideal goals (an individual’s hopes, dreams, and aspirations), and the prevention system, which is associated with ought goals (an individual’s duties, responsibilities, and obligations). The two systems have been studied extensively in behavioral research with reference to differences between promotion and prevention goal pursuit as well as the consequences of perceived attainment versus nonattainment within each system. However, no study has examined the neural correlates of each combination of goal domain and goal attainment status. We used a rapid masked idiographic goal priming paradigm and functional magnetic resonance imaging to present individually selected promotion and prevention goals, which participants had reported previously that they were close to attaining (“match”) or far from attaining (“mismatch”). Across the four priming conditions, significant activations were observed in bilateral insula (Brodmann area (BA) 13) and visual association cortex (BA 18/19). Promotion priming discriminantly engaged left prefrontal cortex (BA 9), whereas prevention priming discriminantly engaged right prefrontal cortex (BA 8/9). Activation in response to promotion goal priming was also correlated with an individual difference measure of perceived success in promotion goal attainment. Our findings extend the construct validity of RFT by showing that the two systems postulated by RFT, under conditions of both attainment and nonattainment, have shared and distinct neural correlates that interface logically with established network models of self-regulatory cognition.

Auto-biological beliefs—beliefs about one’s own biology—are an understudied component of personal identity. Research participants who are led to believe they are biologically vulnerable to affective disorders report more symptoms and less ability to control their mood; however, little is known about the impact of self-originating beliefs about risk for psychopathology, and whether such beliefs correspond to empirically derived estimates of actual vulnerability. Participants in a neuroimaging study (n = 1256) completed self-report measures of affective symptoms, perceived stress, and neuroticism, and an emotional face processing task in the scanner designed to elicit threat responses from the amygdala. A subsample (n = 63) additionally rated their own perceived neural response to threat (i.e., amygdala activity) compared to peers. Self-ratings of neural threat response were uncorrelated with actual threat-related amygdala activity measured via BOLD fMRI. However, self-ratings predicted subjective distress across a variety of self-report measures. In contrast, in the full sample, threat-related amygdala activity was uncorrelated with self-report measures of affective distress. These findings suggest that beliefs about one’s own biological threat response—while unrelated to measured neural activation—may be informative indicators of psychological functioning.

Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.

Cognitive impairment has been identified as an important aspect of major depressive disorder (MDD). We tested two theories regarding the association between MDD and cognitive functioning using data from longitudinal cohort studies. One theory, the cognitive reserve hypothesis, suggests that higher cognitive ability in childhood decreases risk of later MDD. The second, the scarring hypothesis, instead suggests that MDD leads to persistent cognitive deficits following disorder onset. We tested both theories in the Dunedin Study, a population-representative cohort followed from birth to midlife and assessed repeatedly for both cognitive functioning and psychopathology. We also used data from the Environmental Risk Longitudinal Twin Study to test whether childhood cognitive functioning predicts future MDD risk independent of family-wide and genetic risk using a discordant twin design. Contrary to both hypotheses, we found that childhood cognitive functioning did not predict future risk of MDD, nor did study members with a past history of MDD show evidence of greater cognitive decline unless MDD was accompanied by other comorbid psychiatric conditions. Our results thus suggest that low cognitive functioning is related to comorbidity, but is neither an antecedent nor an enduring consequence of MDD. Future research may benefit from considering cognitive deficits that occur during depressive episodes from a transdiagnostic perspective.

Late adolescence and emerging adulthood (specifically ages 15–24) represent a period of heightened sexual risk taking resulting in the greatest annual rates of sexually transmitted infections and unplanned pregnancies in the US population. Ongoing efforts to prevent such negative consequences are likely to benefit from a deepening of our understanding of biological mechanisms through which sexual risk taking emerges and biases decision making during this critical window. Here we present a neuroscience framework from which a mechanistic examination of sexual risk taking can be advanced. Specifically, we adapt the neurodevelopmental triadic model, which outlines how motivated behavior is governed by three systems: approach, avoidance, and regulation, to sexual decision making and subsequent risk behavior. We further propose a testable hypothesis of the triadic model, wherein relatively decreased threat-related amygdala reactivity and increased reward-related ventral striatum reactivity leads to sexual risk taking, which is particularly exaggerated during adolescence and young adulthood when there is an overexpression of dopaminergic neurons coupled with immature top-down prefrontal cortex regulation. We conclude by discussing how future research based on our adapted triadic model can inform ongoing efforts to improve intervention and prevention efforts.

The experience of child maltreatment is a significant risk factor for the development of later internalizing disorders such as depression and anxiety. This risk is particularly heightened after exposure to additional, more contemporaneous stress. While behavioral evidence exists for such “stress sensitization,” little is known about the mechanisms mediating such relationships, particularly within the brain. Here we report that the experience of child maltreatment independent of recent life stress, gender, and age is associated with reduced structural integrity of the uncinate fasciculus, a major white matter pathway between the amygdala and ventromedial prefrontal cortex, in young adults. We further demonstrate that individuals with lower uncinate fasciculus integrity at baseline who subsequently experience stressful life events report higher levels of internalizing symptomatology at follow-up. Our findings suggest a novel neurobiological mechanism linking child maltreatment with later internalizing symptoms, specifically altered structural connectivity within the brain's threat-detection and emotion-regulation circuitry.

As the amygdala is part of the phylogenetic old brain, and its anatomical and functional properties are conserved across species, it is reasonable to assume genetic influence on its activity. A large corpus of candidate gene studies indicate that individual differences in amygdala activity may be caused by genetic variants within monoaminergic signaling pathways such as dopamine, serotonin, and norepinephrine. However, to our knowledge, the use of genome-wide data to discover genetic variants underlying individual differences in adult amygdala activity is novel. In the present study, the combination of genome-wide data and functional imaging phenotypes from an emotional faces task yielded a significant association between rs10014254 and the amygdala using a region of interest approach. This single nucleotide polymorphism is located in a regulatory region upstream of the Paired-like homeobox 2b (PHOX2B) gene; therefore it could affect the expression of this gene. PHOX2B regulates the expression of enzymes necessary for the synthesis of several monoamines and is essential for the development of the autonomic nervous system. However, an attempt to replicate the finding in an independent sample from North America did not succeed. The synthesis of functional magnetic resonance imaging (fMRI) and genome-wide data takes a hypothesis-free approach as to which genetic variants are of interest. Therefore, we believe that an undirected finding within such a plausible region is of interest, and that our results add further support to the hypothesis that monoaminergic signaling pathways play a central role in regulating amygdala activity.

Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy.This research was supported in part by funding from the United Kingdom National Programme on Forensic Mental Health Research and Development (to E.V.), the Medical Research Council Grant G0401170 (to E.V.), the National Institute of Mental Health Grants K01-MH001957 (to D.E.W.) and K01-MH072837 (to A.R.H.), as well as an NARSAD Young Investigator Award (to A.R.H.).