B02: Young offenders’ self-regulation deficit as a common mechanism for aggressive behavior and psychopathology - neural mechanisms and role of adverse childhood experiences

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To reduce mental disorder prevalence, the understanding of resilience to stress-related disorder and its neurobiological mechanisms has come into the focus of biomedical research to develop both biologically rooted prevention and innovative therapeutic approaches for stress-related disorder. While some resilience mechanisms have been exemplified on the molecular, cellular, and brain-regional level, evidence on the neural systems level is rather sparse. We present the first translational evidence of adaptive plasticity in visual microcircuits and top-down modulation onto the visual system as a neurobiological resilience mechanism at the neural systems level in both humans and mice. In humans, we demonstrate that this adaptive microcircuit plasticity is linked to interactions between neurocognitive domains—executive and perceptual—and between brain regions—frontal and occipital—in specific oscillatory frequencies (β band in frontal inferior frontal gyrus and γ band in occipital V2). Additionally, expanding upon prior resilience research, our findings offer further evidence that phenotypic resilience is associated not only with macro- and microcircuit plasticity but also with better performance in neurocognitive functions central to resilience, i.e., perceptual discrimination in mice and cognitive control in humans. In mice, using awake 2-photon calcium imaging, we observed distinct resilient and susceptible network phenotypes in mouse visual cortex. Resilient animals surpassed both susceptible animals and nonstressed controls in their ability to encode visual afferents. This suggests an improved performance supporting the concepts of posttraumatic growth and stress inoculation on a neurobiological level. Resilience at the neural systems level involves active, dynamic processes rather than being merely passive responses to stress and constitutes a first example that neural network states of resilience are metastable, self-stabilizing, and noncontinuous entities that could serve as a target for new neural network interventions for fostering resilience.

The association of adverse childhood experiences (ACEs) with the perpetration of aggressive behavior across the lifespan has repeatedly been demonstrated. However, whereas age-specific impacts of ACEs on neural and psychological development are discussed, little is known about sensitive periods during childhood and adolescence in which ACEs may exert the most severe effects on an individual’s propensity for aggression. Thus, the present study retrospectively assessed ACEs during early childhood (up to 5 years), late childhood (6–11 years), and adolescence (12 years and above) in 204 adults and examined age-dependent relations to current externalizing aggressiveness. Although the general ACE-aggression link could be replicated, no clear evidence emerged for age-specific impacts. While the total ACE burden was highest during adolescence and only ACEs during adolescence were associated with increased adult aggressiveness, the strengths of the relationships between ACEs and aggressiveness did not differ significantly depending on the examined age groups. Nevertheless, our results underscore the need for future research to implement more sophisticated age-sensitive approaches to examine the association of ACEs with aggressive behavior as an important basis for the design of promising prevention and intervention measures.