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Background : Cortisol is a stress-related hormone that interacts with peripheral and neural systems. Although cortisol is important for short-term stress responses, chronically high cortisol is hypothesised to underlie the long-term effects of chronic stress, including decreased dendritic arborisation in rodent prefrontal cortex (PFC). Here we examined the relationship between variation in stress-induced cortisol levels and regional brain volume in 592 young rhesus monkeys. Methods : Cortisol was quantified from blood samples taken from 592 rhesus monkeys (µ-age: 1.88 years; sex: 265 F) immediately after a human intruder presented their profile to the monkey for 30 min. T1-weighted structural MRI scans, taken within 2 weeks of testing, were transformed to an atlas-based study specific template using ANTS (http://www.picsl.upenn.edu/ANTS/). For each subject, we decomposed the final standard-space transformation into affine (linear) and deformable (nonlinear) components. We then produced a 3D map of the relative volume change from the deformable transformation, which accounts for whole-brain differences. Voxelwise robust regression analyses assessed the relationship between cortisol and brain volume, as measured using the log-jacobian determinant. Results : Those subjects with higher cortisol had significant decreases in cortical volume. More specifically, there was a significant negative relationship (FDR, q<0.05, two-tailed) between the log-jacobian and cortisol in cytoarchitectonic areas 47o, 46/9, 46 and 8 within the PFC, as well as motor area 4 and parietal area PGa (MIP). Conclusions : These results provide novel evidence that higher cortisol is associated with less PFC volume in young primates, and builds on previous work examining the relationship between stress and cortical thickness in older adult humans. These data, collected in very young animals, demonstrate that PFC volume and cortisol are negatively associated early in life. These findings are particularly interesting because the PFC regions identified here undergo substantial development throughout late childhood and early adulthood. Moreover, because changes in PFC are thought to underlie the emergence of adult-like cognitive and emotional functioning, our findings may have great relevance to the later development of affective psychopathology.