Regional specificity of sex effects on subcortical volumes across the lifespan in healthy aging

Abstract

When conceptualizing age-specific onsets and sex-specific characteristics of neuropsychiatric diseases in a neurobiological context, it may be crucially important to consider differential trajectories of aging. Here, we investigated effects of age, sex, and their interactions on absolute and relative volumes of subcortical structures with known involvement in psychiatric disorders, including the basal ganglia, thalamus, hippocampus, and amygdala. Structural MRI data of 76 healthy subjects (38 males, 19-70 years) from the ICBM database were analyzed. Age-related absolute atrophy was generally found in the basal ganglia and thalamus, while in the hippocampus decline was only observed in males, and was generally absent in the amygdala. Disproportionate degeneration in the basal ganglia and thalamus, exceeding cortical decline was specific for females. When allowing higher-order models, a quadratic model could better describe the negative relation of absolute volume and age in the basal ganglia in males, and generally in the hippocampus and amygdala. We could show that negative age-relations are highly specific for certain subcortical structures in either gender. Importantly these findings also emphasize the significant impact of analytical strategies when deciding for correction of subcortical volumes to the whole-brain decline. Specifically, in the basal ganglia disproportionate shrinkage in females was suggested by the relative analysis while absolute volume analysis rather stressed an accelerating decline in older males. Given strong involvement of the basal ganglia in both cognitive aging and emotional regulation, our findings may be crucial for studies investigating the onset and prevalence of dementia and depressive symptoms in male and female aging.

Decreased uncinate fasciculus tract integrity in male

“…Therefore, we took the correlation between all tract measures (r = 0.484) into account using the Simple Interactive Statistical Analysis Bonferroni tool (www. quantitativeskills.com/sisa/calculations/bonfer.htm), 47 rendering a p < 0.017 significant. For the segment analysis, a mean correlation coefficient of r = 0.280 was observed, resulting in a corrected α of < 0.011 for these analyses.…”

Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

“…To control for the number of statistical tests we used a Bonferroni correction based on the number of ROIs, adjusted for the correlation be tween the ROIs. 43,44 For the volumes (11 ROIs with an average r of 0.359 between the regions) this resulted in a critical α of 0.01. For the cortical thickness (5 ROIs with an average r of 0.45) and surface area (5 ROIs with an average r of 0.57) calculations the critical α were 0.02 and 0.03, respectively.…”

Perils and pitfalls of reporting sex differences

“…This sex difference is relatively large, as is the difference in total brain volume (figure 2b) [56]. When brain volume is controlled, sex differences in individual brain regions are smaller or disappear completely [66].…”