Genetics of aggressive behavior: An overview.

The Research Domain Criteria (RDoC) address three types of aggression: frustrative non-reward, defensive aggression and offensive/proactive aggression. This review sought to present the evidence for genetic underpinnings of aggression and to determine to what degree prior studies have examined phenotypes that fit into the RDoC framework. Although the constructs of defensive and offensive aggression have been widely used in the animal genetics literature, the human literature is mostly agnostic with regard to all the RDoC constructs. We know from twin studies that about half the variance in behavior may be explained by genetic risk factors. This is true for both dimensional, trait-like, measures of aggression and categorical definitions of psychopathology. The non-shared environment seems to have a moderate influence with the effects of shared environment being unclear. Human molecular genetic studies of aggression are in an early stage. The most promising candidates are in the dopaminergic and serotonergic systems along with hormonal regulators. Genome-wide association studies have not yet achieved genome-wide significance, but current samples are too small to detect variants having the small effects one would expect for a complex disorder. The strongest molecular evidence for a genetic basis for aggression comes from animal models comparing aggressive and non-aggressive strains or documenting the effects of gene knockouts. Although we have learned much from these prior studies, future studies should improve the measurement of aggression by using a systematic method of measurement such as that proposed by the RDoC initiative.

Longitudinal change in the neural bases of adolescent social self-evaluations: effects of age and pubertal development.

Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers' social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a "social reorientation" (Nelson et al., 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N = 27, mean age = 10.1 and 13.1 years at time points one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest that changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.

Structural Brain Abnormalities of Attention-Deficit/Hyperactivity Disorder With Oppositional Defiant Disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is associated with structural abnormalities in total gray matter, basal ganglia, and cerebellum. Findings of structural abnormalities in frontal and temporal lobes, amygdala, and insula are less consistent. Remarkably, the impact of comorbid oppositional defiant disorder (ODD) (comorbidity rates up to 60%) on these neuroanatomical differences is scarcely studied, while ODD (in combination with conduct disorder) has been associated with structural abnormalities of the frontal lobe, amygdala, and insula. The aim of this study was to investigate the effect of comorbid ODD on cerebral volume and cortical thickness in ADHD. METHODS: Three groups, 16 ± 3.5 years of age (mean ± SD; range 7-29 years), were studied on volumetric and cortical thickness characteristics using structural magnetic resonance imaging (surface-based morphometry): ADHD+ODD (n = 67), ADHD-only (n = 243), and control subjects (n = 233). Analyses included the moderators age, gender, IQ, and scan site. RESULTS: ADHD+ODD and ADHD-only showed volumetric reductions in total gray matter and (mainly) frontal brain areas. Stepwise volumetric reductions (ADHD+ODD < ADHD-only < control subjects) were found for mainly frontal regions, and ADHD+ODD was uniquely associated with reductions in several structures (e.g., the precuneus). In general, findings remained significant after accounting for ADHD symptom severity. There were no group differences in cortical thickness. Exploratory voxelwise analyses showed no group differences. CONCLUSIONS: ADHD+ODD and ADHD-only were associated with volumetric reductions in brain areas crucial for attention, (working) memory, and decision-making. Volumetric reductions of frontal lobes were largest in the ADHD+ODD group, possibly underlying observed larger impairments in neurocognitive functions. Previously reported striatal abnormalities in ADHD may be caused by comorbid conduct disorder rather than ODD.

The link between callous-unemotional traits and neural mechanisms of reward processing: An fMRI study.

Callous-unemotional (CU) traits, i.e., unconcernedness and lack of prosocial feelings, may manifest in Conduct Disorder (CD), but also in Oppositional Defiant Disorder (ODD) and Attention Deficit Hyperactivity Disorder (ADHD). These disorders have been associated with aberrant reward processing, while the influence of CU traits is unclear. Using functional Magnetic Resonance Imaging (fMRI), we examined whether CU traits affect the neural circuit for reward. A Monetary Incentive Delay (MID) task was administered to 328 adolescents and young adults with varying levels of CU traits: 40 participants with ODD/CD plus ADHD, 101 participants with ADHD only, 84 siblings of probands with ADHD and 103 typically developing (TD) individuals. During reward anticipation, CU traits related negatively to medial prefrontal cortex (mPFC) activity, independent of ADHD symptoms and ODD/CD diagnosis. Our results indicate that CU traits are a valuable dimension for assessing the neural basis of reward processing.

Sex differences in the neural bases of social appraisals.

Behavioral research has demonstrated an advantage for females compared with males in social information processing. However, little is known about sex-related differences in brain activation during understanding of self and others. In the current functional magnetic resonance imaging study, this was assessed in late adolescents (aged 18-19) and young adults (aged 23-25) when making appraisals of self and other as well as reflected self-appraisals. Across all groups and for all appraisal conditions, activation was observed in the medial prefrontal cortex, medial posterior parietal cortex, left and right dorsolateral prefrontal cortex and left posterior parietal cortex. Males activated the medial posterior parietal cortex and bilateral temporoparietal junction more than females. The precuneus showed stronger activation in males compared with females specifically during appraisals of others. No differences between late adolescents and young adults were found. These results indicate that sex differences exist in the neural bases of social understanding.

Changes in neural mechanisms of cognitive control during the transition from late adolescence to young adulthood.

The transition from late adolescence to young adulthood is marked by anatomical maturation of various brain regions. In parallel, defining life changes take place, such as entrance into college. Up till now research has not focused on functional brain differences during this particular developmental stage. The current cross-sectional fMRI study investigates age differences in cognitive control by comparing late adolescents, 18-19 years old, with young adults, 23-25 years old. Seventy-four male and female medical students carried out a combined cognitive and emotional Stroop task. Overall, lateral frontoparietal and medial parietal activation was observed during cognitive interference resolution. Young adults showed stronger activation in the dorsomedial prefrontal cortex, left inferior frontal gyrus, left middle temporal gyrus and middle cingulate, compared to late adolescents. During emotional interference resolution, the left precentral and postcentral gyrus were involved across age and sex. The dorsomedial prefrontal cortex and precuneus were activated more in young adults than in late adolescents. No sex-related differences were found in this homogeneous sample. The results suggest that the neural bases of cognitive control continue to change between late adolescence and young adulthood.

The effect of perspective and content on brain activation during mentalizing in young females.

In the present functional magnetic resonance imaging (fMRI) study, we investigated the role of different brain regions in separate aspects of mentalizing. Young females aged 18-19 years were asked to imagine a social situation and answer a question. Perspective, self and other, as well as content, emotion, and behavior, were varied. Activation was observed in the left precuneus, left temporoparietal junction, left medial prefrontal cortex and left middle temporal gyrus. Left precuneus and left temporoparietal junction were recruited more when taking the perspective of other than when taking the perspective of self. Medial prefrontal areas might be more involved during mentalizing about emotion versus baseline than about behavior versus baseline.

Functional connectivity between brain regions involved in learning words of a new language.

Previous studies have identified several brain regions that appear to be involved in the acquisition of novel word forms. Standard word-by-word presentation is often used although exposure to a new language normally occurs in a natural, real world situation. In the current experiment we investigated naturalistic language exposure and applied a model-free analysis for hemodynamic-response data. Functional connectivity, temporal correlations between hemodynamic activity of different areas, was assessed during rest before and after presentation of a movie of a weather report in Mandarin Chinese to Dutch participants. We hypothesized that learning of novel words might be associated with stronger functional connectivity of regions that are involved in phonological processing. Participants were divided into two groups, learners and non-learners, based on the scores on a post hoc word recognition task. The learners were able to recognize Chinese target words from the weather report, while the non-learners were not. In the first resting state period, before presentation of the movie, stronger functional connectivity was observed for the learners compared to the non-learners between the left supplementary motor area and the left precentral gyrus as well as the left insula and the left rolandic operculum, regions that are important for phonological rehearsal. After exposure to the weather report, functional connectivity between the left and right supramarginal gyrus was stronger for learners than for non-learners. This is consistent with a role of the left supramarginal gyrus in the storage of phonological forms. These results suggest both pre-existing and learning-induced differences between the two groups.