Resilience and young people's brain structure, function and connectivity: A systematic review.

Although negative early life experiences are associated with an increased risk of developing psychopathology, some individuals exposed to childhood adversity demonstrate psychological resilience. Little is known about the neural correlates of resilience, especially in young people. To address this gap, we conducted a systematic review of neuroimaging studies of resilience in youth. The PubMed, Web of Science, Scopus, and PsycINFO databases were searched; 5,482 studies were identified. Following title/abstract screening, and full reading of the remaining articles, 22 studies based on 19 unique datasets were included. We found preliminary evidence that resilience is associated with structural, functional, and connectivity differences in young people, as assessed using structural and functional MRI and diffusion tensor imaging methods. Despite heterogeneity in definitions/assessment of resilience and a limited number of studies, the neuroimaging literature suggests some convergence across modalities regarding brain regions linked to resilience (especially the prefrontal cortex). Future studies would benefit from adopting longitudinal designs, broader conceptualisations of resilience that capture the impact of adversity exposure, and a dimensional approach to psychopathology.

Hypothalamic-Pituitary-Adrenal Axis Function in Children and Adults with Severe Antisocial Behavior and the Impact of Early Adversity.

PURPOSE OF REVIEW: To review recent studies investigating hypothalamic-pituitary-adrenal axis function in children and adolescents with disruptive behavior disorders (DBDs) and adults with antisocial personality disorder. We consider key concepts and methodological issues in cortisol assessment and review studies investigating basal cortisol secretion and stress reactivity in antisocial populations. Lastly, we consider whether cortisol abnormalities predict prognosis or treatment outcomes and the impact of exposure to adversity on hypothalamic-pituitary-adrena (HPA) axis activity. RECENT FINDINGS: Studies tracking cortisol levels across the day and assessing cortisol awakening responses (CARs) have reported broadly intact, but flatter, diurnal rhythms and lower CARs in children and adolescents with DBDs, whereas findings in antisocial adults have been mixed. Cortisol hyporeactivity to stress is consistently reported in male antisocial populations, whereas no comparable data exist in females. Severe antisocial behavior is associated with cortisol hyporeactivity to stress, and such hyporeactivity predicts poor treatment outcomes. Further research investigating sex differences and the impact of adversity is needed. Harmonization of methods for assessing hypothalamic-pituitary-adrenal axis function and antisocial behavior would enhance progress in this area.

Tuftsin binds neuropilin-1 through a sequence similar to that encoded by exon 8 of vascular endothelial growth factor.

Tuftsin, Thr-Lys-Pro-Arg (TKPR), is an immunostimulatory peptide with reported nervous system effects as well. We unexpectedly found that tuftsin and a higher affinity antagonist, TKPPR, bind selectively to neuropilin-1 and block vascular endothelial growth factor (VEGF) binding to that receptor. Dimeric and tetrameric forms of TKPPR had greatly increased affinity for neuropilin-1 based on competition binding experiments. On endothelial cells tetrameric TKPPR inhibited the VEGF(165)-induced autophosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) even though it did not directly inhibit VEGF binding to VEGFR-2. Homology between exon 8 of VEGF and TKPPR suggests that the sequence coded for by exon 8 may stabilize VEGF binding to neuropilin-1 to facilitate signaling through VEGFR-2. Given the overlap between processes involving neuropilin-1 and tuftsin, we propose that at least some of the previously reported effects of tuftsin are mediated through neuropilin-1.