Structural neuroimaging studies have provided evidence of differences in local brain volume between cocaine-dependent and healthy control individuals. While sex differences in aetiology, course and brain dysfunction associated with chronic cocaine abuse have been previously documented, evidence of sex-specific differences in brain volume has not been examined thus far. This study examined sex-related differences in grey matter volume between cocaine-dependent and healthy control subjects using voxel-based morphometry. High-resolution T1 structural scans were obtained from 36 inpatient, treatment-engaged 3-week abstinent cocaine-dependent (CD) individuals. Fifty healthy control subjects were also scanned. Segmentation and registration were performed in SPM8, using New Segment and DARTEL, respectively. The whole-brain statistical analysis was conducted in SPM8 using random field-based cluster-size testing and family-wise error rate correction for multiple comparisons. CD patients were found to have less grey matter volume in anterior prefrontal cortex, including frontopolar and orbitofrontal cortices, and a posterior region surrounding the parietal-occipital sulcus. Female CD patients had less grey matter volume than female controls in left inferior frontal gyrus, insula, superior temporal gyrus and hippocampus. Male CD patients had less grey matter in a superior cortical region that included the precentral gyrus and the mid-cingulate. These sex differences in lower grey matter volume add to the evidence from functional neuroimaging for sex-specific differences in the neurophysiological changes associated with chronic cocaine use.

Fingolimod is an approved therapeutic option for patients with relapsing-remitting multiple sclerosis that primarily functions by sequestering T cells in lymph nodes inhibiting their egress to the central nervous system. However, recent data suggests that Fingolimod may also directly affect the immune cell function. Here we examined the in vivo effects of Fingolimod in modulating the phenotype and function of T cell and Foxp3 regulatory T cell populations in patients with multiple sclerosis under Fingolimod treatment. Besides decreasing the cell numbers in peripheral blood and sera levels of pro-inflammatory cytokines, Fingolimod inhibited the expression of Th1 and Th17 cytokines on CD4+ T cells and increased the expression of exhaustion markers. Furthermore, treatment increased the frequency of regulatory T cells in blood and inhibited the Th1-like phenotype that is characteristic of patients with multiple sclerosis, augmenting the expression of markers associated with increased suppressive function. Overall, our data suggest that Fingolimod performs other important immunomodulatory functions besides altering T cell migratory capacities, with consequences for other autoimmune pathologies characterized by excessive Th1/Th17 responses and Th1-like regulatory T cell effector phenotypes.