Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates

Abstract

Male bonnet monkeys (Macaca radiata) were subjected to the Variable Foraging Demand (VFD) early stress paradigm as infants, MRI scans were completed an average of four years later, and behavioral assessments of anxiety and ex-vivo corpus callosum (CC) measurements were made when animals were fully matured. VFD rearing was associated with smaller CC size, CC measurements were found to correlate with fearful behavior in adulthood, and ex-vivo CC assessments showed high consistency with earlier MRI measures. Region of Interest (ROI) hippocampus and whole brain voxel- based morphometry assessments were also completed and VFD rearing was associated with reduced hippocampus and inferior and middle temporal gyri volumes. Animals were also characterized according to serotonin transporter genotype (5-HTTLPR), and the effect of genotype on imaging parameters was explored. The current findings highlight the importance of future research to better understand the effects of stress on brain development in multiple regions, including the corpus callosum, hippocampus, and other regions involved in emotion processing. Nonhuman primates provide a powerful model to unravel the mechanisms by which early stress and genetic makeup interact to produce long-term changes in brain development, stress reactivity, and risk for psychiatric disorders.

Previous Institutionalization Is Followed by Broader Amygdala–Hippocampal–PFC Network Connectivity during Aversive Learning in Human Development

“…During adolescence, striking changes in amygdalahippocampal-mPFC connectivity are observed (Pattwell et al, 2011), and, by adulthood, aversive learning is supported by strong interconnections among the amygdala, hippocampus, and mPFC in nonhuman animals (LeDoux et al, 1990;Corcoran and Quirk, 2007;Sierra-Mercado et al, 2011) and human adults (Fullana et al, 2016;Greco and Liberzon, 2016). Rodent models have revealed that maternal separation leads to precocious prefrontal and hippocampal maturation (Huang et al, 2005;Muhammad et al, 2012), and adult-like aversive learning and anxiety during development (Moriceau and Sullivan, 2006;Ono et al, 2008;Callaghan and Richardson, 2011). Importantly, while maternal deprivation accelerates aversive-learning processes, it may slow or impair cognitive development (Hulshof et al, 2011), suggesting that stress-induced changes are not uniform.…”

“…Rodent models have revealed that maternal separation leads to precocious prefrontal and hippocampal maturation (Huang et al, 2005;Muhammad et al, 2012), and adult-like aversive learning and anxiety during development (Moriceau and Sullivan, 2006;Ono et al, 2008;Callaghan and Richardson, 2011). Importantly, while maternal deprivation accelerates aversive-learning processes, it may slow or impair cognitive development (Hulshof et al, 2011), suggesting that stress-induced changes are not uniform. This is in line with broader evidence suggesting that cognitive and emotional trajectories are not uniform in typical or atypical development (Reichenberg et al, 2010).…”

Early-life stress has persistent effects on amygdala function and development in mice and humans

“…Adult-restraint stress leads to reversible decreases in dendritic arborization and volume in prefrontal and hippocampal brain regions (16)(17)(18) but lasting amygdaloid neuronal hypertrophy and anxiety-like behavior (19). In contrast, studies of ELS (20)(21)(22)) (e.g., removal of the dam) show deficits in adult hippocampal-dependent memory but inconsistent effects on anxiety-like behaviors (15,23,24), with the specific type of deficit varying as a function of task and age of testing. For example, Raineki et al showed that ELS leads to social behavioral deficits in preweaned rodents but later depressive-like symptoms in adolescent rodents (25).…”

CCKergic System, Hypothalamus-Pituitary-Adrenal (HPA) Axis, and Early-Life Stress (ELS)

“…Generally, it is now accepted that ELS can produce changes, most permanently, at multiple levels [25,27]. Following ELS, for example, the overall volume of the hippocampus [28][29][30], corpus callosum [31][32][33], and cortex [34][35][36] all becomes smaller, compared to that of those brain regions in age-matched subjects. Besides these neuroanatomical changes, the neuronal activity and the synaptic function in the brain in ELS-victims are impaired [37][38][39], and most neurotransmitter systems are significantly affected too.…”