Changes in neuroplasticity following early-life social adversities: the possible role of brain-derived neurotrophic factor

Abstract

Social adversities experienced in childhood can have a profound impact on the developing brain, leading to the emergence of psychopathologies in adulthood. Despite the burden this places on both the individual and society, the neurobiological aspects mediating this transition remain unclear. Recent advances in preclinical and clinical research have begun examining neuroplasticity-the nervous system's ability to form adaptive changes in response to new experience-in the context of early-life vulnerability to social adversities and plasticity-related alterations following such traumatic events. A key mediator of plasticity-related molecular processes is the brain-derived neurotrophic factor (BDNF), which has also been implicated in various psychiatric disorders related to childhood social adversities. Preclinical and clinical data suggest early-life social adversities (ELSA) might be associated with accelerated maturation of social network circuitry, a possible ontogenic adaptation to the adverse environment. Neural plasticity decreases by adulthood, lessening the efficacy of treatment in ELSA-related psychiatric disorders. However, literature data suggest that by increasing BDNF/TrkB signalling through antidepressant treatment a juvenile-like plasticity state can be induced, which allows for reorganization of the social circuitry when guided by psychotherapy and surrounded by a safe and positive environment.

Subcortical structural variations associated with low socioeconomic status in adolescents

“…A handful of studies have found smaller volumes among lower‐SES youth (Hanson et al, ; Luby et al, ; McDermott et al, ), but most do not, and it remains unclear what accounts for the differences. As with the hippocampus, discussed in the following section, BDNF could account for the positive associations between SES and amygdala curvature in males as abnormalities in BDNF methylation and mRNA expression in the amygdala are associated with early life adversity (Miskolczi et al, ).…”

“…Regions that are important for the regulation of social behavior, including subcortical regions such as the hippocampus, basal ganglia, and amygdala, undergo protracted development which renders them vulnerable to experience-dependent changes influenced by the environment for prolonged time periods (Miskolczi, Halasz, & Mikics, 2019). These time epochs of adaptive and dynamic brain changes are known as sensitive periods, and are regulated in part by brain-derived neurotrophic factor (BDNF; Miskolczi et al, 2019). BDNF reaches peak levels in adolescence and is involved in regulation of programmed cell death, synaptic pruning, and axonal and dendritic branching of rapidly proliferating and differentiating neurons (Yang et al, 2009).…”

“…BDNF reaches peak levels in adolescence and is involved in regulation of programmed cell death, synaptic pruning, and axonal and dendritic branching of rapidly proliferating and differentiating neurons (Yang et al, 2009). Early life social adversity results in abnormalities in BDNF methylation and mRNA expression, including in the hippocampus and amygdala (Miskolczi et al, 2019). Also, there are sex differences in BDNF expression (Bath, Schilit, & Lee, 2013) and sensitive periods, and associated effects on amygdala and hippocampal volume (Pechtel, Lyons-Ruth, Anderson, & Teicher, 2014;Teicher et al, 2018).…”

“…Also, there are sex differences in BDNF expression (Bath, Schilit, & Lee, 2013) and sensitive periods, and associated effects on amygdala and hippocampal volume (Pechtel, Lyons-Ruth, Anderson, & Teicher, 2014;Teicher et al, 2018). In their model, Miskolczi et al (2019) argue that sex (along with genetic factors) influence brain developmental curves, that the trajectory of these developmental curves are region-specific and furthermore determine the timing of sensitive periods for each region, and that depending on the timing of the early life adversity, separable brain regions might undergo disturbed development, resulting in aberrant maturation and increased risk of psychopathology.…”

Weak correlations between body height and several brain metrics in healthy elderly subjects

“…Preclinical signs of dementia, for example may impact on the brain measures and may lead to earlier or accelerated decline although cognition is still normal (Costafreda et al., ; Gaser, Franke, Klöppel, Koutsouleris, & Sauer, ). Stress or unfavourable genetic configurations (e.g., genes coding pathologies like Huntington's disease or Down syndrome) may be other factors in determining brain structural decline (Bhatt et al., ; Mattson, Chan, & Duan, ; Miskolczi, Halász, & Mikics, ). Most important, however, is the possibility that the usage and non‐usage of specific psychological and motor functions have an influence on brain size.…”