Impact of gonadectomy on maturational changes in brain volume in adolescent macaques

Abstract

Adolescence is a transitional period between childhood and adulthood characterized by significant changes in global and regional brain tissue volumes. It is also a period of increasing vulnerability to psychiatric illness. The relationship between these patterns and increased levels of circulating sex steroids during adolescence remains unclear. The objective of the current study was to determine whether gonadectomy, prior to puberty, alters adolescent brain development in male rhesus macaques. Ninety-six structural MRI scans were acquired from 12 male rhesus macaques (8 time points per animal over a two-year period). Six animals underwent gonadectomy and 6 animals underwent a sham operation at 29 months of age. Mixed-effects models were used to determine whether gonadectomy altered developmental trajectories of global and regional brain tissue volumes. We observed a significant effect of gonadectomy on the developmental trajectory of prefrontal gray matter (GM), with intact males showing peak volumes around 3.5 years of age with a subsequent decline. In contrast, prefrontal GM volumes continued to increase in gonadectomized males until the end of the study. We did not observe a significant effect of gonadectomy on prefrontal white matter or on any other global or regional brain tissue volumes, though we cannot rule out that effects might be detected in a larger sample. Results suggest that the prefrontal cortex is more vulnerable to gonadectomy than other brain regions.

Keywords: Adolescent; Macaca mulatta; Magnetic resonance imaging; Prefrontal cortex; Testosterone.

Figure 1:

Log-testosterone trajectories for each monkey with fit lines based on the polynomial functions in Table 1.

Figure 2:

Observed trajectories for intracranial volume (ICV) and prefrontal GM with fit lines based on the polynomial functions in Table 4.