Sexually dimorphic gray matter changes evident in patients with prior stimulant abuse

1. Women with stimulant dependence after prolonged abstinence had significant changes in gray matter volume that were not observed in men.

2. Significant decreases in gray matter volume were observed in regions corresponding to reward, learning, executive function and affective processing in women but not men, and the volume of the nucleus accumbens, or reward center, was negative correlated with disease severity.

Evidence Rating: 1 (Excellent)

Study Rundown: Substance abuse disorders have been associated with neuroanatomic changes in patients, but there has been limited evaluation of the role of anatomic sex on these neuroanatomic changes amongst patients with stimulant dependence. In this prospective cohort study, age and sex matched subjects who were undergoing treatment for stimulant dependence were evaluated using magnetic resonance imaging to identify neuroanatomic differences after a roughly 3 week period of abstinence. There were significant changes in gray matter volume according to sex in various areas of the brain, including regions associated with reward, learning, executive function and affective processing, such as the insula, orbitofrontal cortex, cingulate cortex, medial frontal gyrus and nucleus accumbens, among others. Compared with female control subjects, women with stimulant dependence showed decreased gray matter volume in these regions, while no changes were seen amongst the male cohort. Of particular interest, the volume of the nucleus accumbens, a region typically associated with reward processing, was negatively correlated with disease severity in female subjects. Additionally, there were statistically significant differences in behavioral approach and impulsivity scores that correlated with gray matter changes in women but not in men.

This study is important in suggesting that there exist sexually dimorphic neuroanatomical differences in patients with stimulant dependence, and that these changes correlate with behavior. Furthermore, these findings suggest that there might be other key differences in how the brain-behavior relationship affects the psychological differences between the sexes in dependence, and may aid in evaluating new approaches to diagnosis and treatment. This study was limited by its overall small size, including only 59 dependence patients, and by the fact that patients addicted to a heterogenous group of stimulants were included, rather than specifying a single type. Future studies should try to perform substance specific analyses, while widening the patient pool to multiple centers in an effort to extrapolate results to a more general patient population.

Click to read the study in Radiology

Relevant reading: Abnormal Brain Structure Implicated in Stimulant Drug Addiction

In-Depth [prospective cohort]: A total of 127 age- and sex-matched subjects (68 control subjects and 59 patients with mixed stimulant abuse) were enrolled prospectively to undergo 3T magnetic resonance imaging of the brain. Specifically, T1-weighted spoiled gradient echo inversion recovery was performed on all subjects, and after adjusting for age, education, and head size, data were obtained on the differences according to sex in gray matter volume of various brain regions. Additionally, these age and sex matched subjects were evaluated for differences in behavioral approach, dependence symptom count, impulsivity, drug exposure, abstinence duration, and years of drug abuse. Mean length of abstinence before imaging was 3 weeks. Patients were recruited from a residential treatment program for those with stimulant dependence including methamphetamine, cocaine, or amphetamine-class substances, and all had been previously diagnosed with substance dependence based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Controls were excluded for dependence on other substances, excluding tobacco. There was no significant difference in gray matter volume between male control subjects and men with stimulant dependence (p = 0.625). Overall, volume changes in the frontal, parietal, temporal, insular and subcortical gray matter regions were significantly decreased in women (p < 0.001) but not in men  (p = 0.625). In particular, volumes were most decreased in the insula (p < 0.001), orbitofrontal cortex (p = 0.003), cingulate cortex (p = 0.005), medial frontal gyrus (p = 0.006), and the nucleus accumbens. Dependence symptom count had a negative correlation with gray matter volume in the nucleus accumbens in women (left: r = -0.364, p = 0.47, right: r = -0.407, p = 0.031 ) but not in men (left: r = -0.063, p = 0.737, right: r = -0.174, p =.349). Among women with stimulant dependence, behavioral approach (p = 0.002) and impulsivity (p = 0.013) were negatively correlated with their respective frontal and temporal gray matter volume changes, which were not found in other groups.

Image: PD

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