Sex differences in impulsivity and brain volumes in methamphetamine users

Abstract

Methamphetamine (METH) is an addictive stimulant adversely affecting brain structure and function. The aim of this study was to investigate impulsivity and brain structures, and sex differences on these variables, between METH users and non-drug user controls (CON). Structural MRI was performed in 124 subjects: 62 METH (ages 41.2±1.4 years, 34 males, 28 females) and 62 CON (ages 43.3±2.3 years, 36 males, 26 females). FreeSurfer 5.1 automated morphometry was used to measure brain morphometry. Subjects completed the Barratt Impulsiveness Scale (BIS) questionnaire, which measures six factors. 2-way and repeated measures ANCOVA, co-varying for age, education, depressive symptoms, and intracranial volume, evaluated for independent and interactive effects of group status and sex. Relationships between METH usage characteristics, brain volumes, and impulsivity scores with significant group differences were examined with Pearson correlations. METH users had higher impulsivity scores in a majority of the factors (p<0.001-0.05). Male METH users had larger right superior frontal volumes compared to CON, while female METH users had smaller volumes compared to CON (p=0.02). Groupby-volume interactions were found in the right superior frontal (p=0.02) and right insula (p=0.02). In the male METH users, greater volumes in these regions were associated with less self-control. Female METH users had larger accumbens compared to female CON (p=0.03). METH users had consistently thinner left frontal cortical regions compared to CON (p=0.003). Consistent with prior reports, METH users were more impulsive and had thinner left frontal cortices than CON. Male METH users had larger superior frontal and insula volumes than CON, which was associated with less self-control (p=0.009-0.05). This was not seen in the female METH users, possibly due to a protective effect of estrogen from neuroinflammation in these regions. This suggests that men and women may be affected differently, and sex should be accounted for in brain morphometry studies.