Chronic Psychosocial Stress and Experimental Pubertal Delay Affect Socioemotional Behavior and Amygdala Functional Connectivity in Adolescent Female Rhesus Macaques

Abstract

In females, pubertal onset appears to signal the opening of a window of increased vulnerability to the effects of stress on neurobehavioral development. What is the impact of pubertal timing on this process? We assessed the effects of pubertal timing and stress on behavior and amygdala functional connectivity (FC) in adolescent female macaques, whose social hierarchy provides an ethologically valid model of chronic psychosocial stress. Monkeys experienced puberty spontaneously (n=34) or pubertal delay via Lupron treatment from age 16-33 months (n=36). We examined the effects of stress (continuous dimension spanning dominant/low-stress to subordinate/high-stress) and experimental pubertal delay (Lupron-treated vs. Control) on socioemotional behavior and FC at 43-46 months, after all animals had begun puberty. Regardless of treatment, subordinate monkeys were more submissive and less affiliative, and exhibited weaker FC between amygdala and dorsolateral prefrontal cortex and stronger FC between amygdala and temporal pole. Regardless of social rank, Lupron-treated monkeys were also more submissive, less affiliative, and explored less in a “Human Intruder” task but were less anxious than untreated monkeys; they exhibited stronger FC between amygdala and orbitofrontal cortex. No interactions between rank and Lupron treatment were observed. These data suggest that some of the effects of chronic subordination stress and delayed puberty overlap behaviorally, such that late-onset puberty-linked exposure to female hormones mimics chronic stress. In the brain, however, delayed puberty and subordination stress had separable effects, suggesting that the overlapping socioemotional outcomes may be mediated by distinct neuroplastic mechanisms. To gain further insights, additional longitudinal studies are required.

The Impact of Suppressing Puberty on Neuropsychological Function

“…In male sheep, impairments in spatial memory associated with the treatment were not fully reversed following discontinuation of treatment 51 . Significant effects of treatment were also evident on measures of brain structure including overall volume 53 , functional connectivity 52 and neuronal density 54 .…”

“…The majority of these studies (n=8) have been conducted in the same flock of sheep using twin controls 10,11,[46][47][48][49][50][51] . Two studies in monkeys 52,53 and one mouse study 54 were also identified. Measures of brain structure were reported in 5 studies and included structural MRI, resting state functional MRI and histopathology (see Table 1).…”

The Impact of Suppressing Puberty on Neuropsychological Function

“…In male sheep, impairments in spatial memory associated with the treatment were not fully reversed following discontinuation of treatment 51 . Significant effects of treatment were also evident on measures of brain structure including overall volume 53 , functional connectivity 52 and neuronal density 54 .…”

“…The majority of these studies (n=8) have been conducted in the same flock of sheep using twin controls 10,11,[46][47][48][49][50][51] . Two studies in monkeys 52,53 and one mouse study 54 were also identified. Measures of brain structure were reported in 5 studies and included structural MRI, resting state functional MRI and histopathology (see Table 1).…”