Clinical vitamin D levels are associated with insular volume and inferior temporal gyrus white matter surface area in community-dwelling individuals with knee pain

Abstract

Context: Vitamin D is an essential, fat soluble micronutrient long-known for its effects on calcium homeostasis and bone health. With advances in technology, it is being discovered that Vitamin D exerts its effects beyond the musculoskeletal system. Vitamin D has since been noted in nervous system health and functioning, and is becoming a target of interest in brain health, aging, and chronic pain outcomes.

Objectives: We and others have previously shown that deficient Vitamin D status is associated with greater pain severity across a variety of conditions, however the reason as to why this relationship exists is still being understood. Here, we sought to examine associations between Vitamin D status and brain structure in those with chronic knee pain.

Methods: Structural MRI imaging techniques and whole brain analyses were employed and serum Vitamin D were collected on 140 participants with chronic pain. Covariates included age, sex, race and site, as these data were collected at two separate institutions. ANOVAs using the clinical cut points for Vitamin D status (deficient, insufficient, and optimal) as well as continuous regression-based Vitamin D effects were employed to observe differences in brain volume. P-value was set to 0.017 after correction for multiple comparisons.

Results: We discovered that individuals in our sample (age = 50+; 63.6% female; 52.1% Non-Hispanic Black) who were either clinically deficient (<20 ng/mL) or insufficient (20-30 ng/mL) in serum Vitamin D had significant differences in the gray matter of the left circular insular cortex, left inferior temporal gyrus, right middle temporal gyrus, as well as decreased white matter surface area in the right inferior temporal gyrus compared to those considered to have optimal levels (>30 ng/mL) of serum Vitamin D.

Conclusion: Evidence from these data suggests that Vitamin D, or lack thereof, may be associated with pain outcomes by mediating changes in regions of the brain known to process and interpret pain. More research understanding this phenomenon as well as the effects of Vitamin D supplementation is warranted.

Keywords: brain; chronic pain; insula; vitamin D; white matter.

FIGURE 1

(A) The Jacobian white matter surface area in a cortical cluster overlapping with the right inferior temporal gyrus {region of the Destrieux atlas [FreeSurfer aparc.a2009s (Destrieux et al., 2010)] containing the maximum T-statistics} was higher for individuals with insufficient Vitamin D levels compared to those with optimal levels. To ease visual interpretation, we have used red to represent the significant positive “Insufficient – Optimal” contrast. (B) Box-plots depicting the distribution of the Jacobian white in the cortical vertex where the T-statistics of this group comparison was maximum for each Vitamin D level group.

FIGURE 2

(A) The volume of in a cortical cluster overlapping with inferior segment of the left circular sulcus of the insula {region of the Destrieux atlas [FreeSurfer aparc.a2009s (Destrieux et al., 2010)] containing the maximum T-statistics} was higher for individuals with deficient Vitamin D levels compared to those with optimal levels. To ease visual interpretation, we have used blue to represent the significant positive “Deficient – Optimal” contrast. (B) Box-plots depicting the distribution of the cortical thickness in the cortical vertex where the T-statistics of this group comparison was maximum for each Vitamin D level group.

FIGURE 3

(A) The area of two cortical clusters overlapping with the left inferior and right middle temporal gyri {regions of the Destrieux atlas [FreeSurfer aparc.a2009s (Destrieux et al., 2010)] containing the maximum T-statistics} was higher for individuals with higher Vitamin D status. To ease visual interpretation, we have used red to represent the significant positive Vitamin D status-area correlation. Scatter plots of the cortical area in the cortical vertices where the T-statistics of these regressions were maximum, versus each Vitamin D status, are shown in panels (B,C).