EFFECTS OF LOW SOCIAL STATUS ON SOCIO-EMOTIONAL BRAIN CIRCUITS – A LONGITUDINAL STUDY IN ADULT FEMALE MACAQUES

Chronic social stress is a risk factor for physical and mental illness and aging-related disorders. We examined long-term effects of lifelong low social status (subordination -SUB- stress) on (1) structure and connectivity of stress/emotional and social regulatory neurocircuits; and (2) biological and neurotoxic mechanisms in a rhesus monkey model.
Brain structural MRI and DTI scans were collected in 27 adult female rhesus monkeys (13 dominant -DOM-, 14 SUB), across 3 years, to examine volume of and connectivity strength between regions in these circuits, including hippocampus, amygdala, superior temporal sulcus (STS), inferior temporal area (TE), prefrontal cortex (PFC) subregions. Plasma biomarkers of stress (cortisol), oxidative stress (thiobarbituric acid-reactive substances -TBARS) and CSF markers of neurotoxicity (kynurenic acid -KYNA, neuroprotective-; quinolinic acid -QA, neurotoxic-) were also measured in adulthood.
Subordinate animals showed 1) larger amygdala (RANKxAGE effect: F_2,23.537=4.342, p=0.025), rostral hippocampus (RANK effect: F_1,22.199=5.790, p=0.025) and STS volumes (RANK effect: F_1,24.179=4.966, p=0.035); 2) higher white matter micro-organization in the uncinate fasciculus (UF RANK effect, Left: F_1,23=4.749, p=0.04, Right: F_1,23=6.244, p=0.02); 3) higher levels of stress markers (cortisol (F_(1,18)=5.323; p=0.033); TBARS (F_(1,18)=4.526; p=0.047)); and 4) lower CSF KYNA levels (F_1,24=5.36, p=0.029) than DOM. Discriminant function analysis revealed that hippocampal volume, KYNA, cortisol and TBARS levels together best differentiated individuals based on social RANK (Wilks’ Lambda=.321, χ²(5)=18.75, p=.002, with strong canonical correlation: .824).
In summary, lifelong low social status led to elevated levels of stress hormones, oxidative stress and enlargement and stronger connectivity in brain circuits important for socio-emotional information processing in adulthood.