Sex differences in decreased limbic and cortical grey matter volume in cocaine dependence: a voxel‐based morphometric study

Abstract

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.

Sex Differences in Gray Matter Changes and Brain-Behavior Relationships in Patients with Stimulant Dependence

“…Authors of some studies (15)(16)(17) primarily have recruited men to exclude the confounding effects of sex, and other investigators (2,18,19) have not included sex as a factor in their analyses of gray matter in patients with stimulant dependence. In fact, to our knowledge, only two studies (20,21) have included descriptions of structural differences between the sexes in patients with stimulant dependence. Rando et al (21) reported lower GMV in the left inferior frontal medial frontal gyrus, anterior cingulate gyrus, insula, and nucleus accumbens in patients with stimulant dependence (2,3).…”

“…In fact, to our knowledge, only two studies (20,21) have included descriptions of structural differences between the sexes in patients with stimulant dependence. Rando et al (21) reported lower GMV in the left inferior frontal medial frontal gyrus, anterior cingulate gyrus, insula, and nucleus accumbens in patients with stimulant dependence (2,3). In the largest meta-analysis of stimulant dependence to date, Ersche et al (2) reported significant decreases in gray matter in the insula, ventromedial prefrontal cortex, inferior frontal gyrus, anterior cingulate gyrus, and anterior thalamus.…”

“…These differences between the sexes could reflect a greater neuroanatomic endophenotype in women that predisposes them to stimulant dependence or a vulnerability to morphologic changes that result from stimulant dependence. Decreased GMV in women with stimulant dependence compared Few previous studies have been focused on the investigation of sexual dimorphism in GMV in patients with stimulant dependence; in fact, authors of only two studies reported structural sex differences in persons with stimulant dependence: Rando et al (21) and Tanabe et al (20). Consistent with our results, Rando et al's (21) findings showed greater GMV in healthy subjects than in women with cocaine dependence in the left inferior frontal gyrus, left insula, left superior temporal gyrus, right temporooccipital cortex, and left hippocampus.…”

Compulsive sexual behavior: Prefrontal and limbic volume and interactions

“…A recent meta‐analysis of 9 studies and 296 alcohol dependent individuals found significantly reduced prefrontal gray matter (GM) volumes, including anterior cingulate cortex (ACC) [Xiao et al, 2015], with frontal cortical GM volume being negatively associated with lifetime alcohol use [Taki et al, 2006]. Prefrontal GM volumes were similarly reduced in cocaine dependent individuals, including in orbitofrontal cortex (OFC) [Rando et al, 2013; Tanabe et al, 2009], anterior prefrontal cortex [Rando et al, 2013] and ACC [Connolly et al, 2013], the latter associated with years of drug use [Connolly et al, 2013]. …”

Hippocampal volume mediates the relationship between measures of pre-treatment cocaine use and within-treatment cocaine abstinence

“…However, findings regarding the volumes of the amygdala and hippocampus in cocaine-dependent patients are less consistent. One study reported increased volume in the amygdala (Ersche et al, 2012), several studies reported reduced volume in at least one of the two structures (Alia-Klein et al, 2011; Makris et al, 2004; Moreno-Lopez et al, 2012; Rando et al, 2013), and several studies did not find volumetric differences (Jacobsen et al, 2001; Narayana et al, 2010; Sim et al, 2007); reviewed in (Mackey and Paulus, 2013)).…”