Childhood maltreatment and amygdala connectivity in methamphetamine dependence

Abstract

Aims: Methamphetamine (METH) is an addictive stimulant known to adversely affect behavior and the brain. The aim of this study was to investigate impulsivity and brain structures, and possible sex differences on these variables, between METH users and non-drug user controls (CON). Methods: 101 subjects completed the Barratt Impulsiveness Scale (BIS) questionnaire and structural brain MRI: 52 METH (ages 41.6±1.5 years, 30 males, 22 females) and 49 CON (ages 45.0±2.3 years, 30 males, 19 females). Automated morphometry in FreeSurfer 5.1 was used to measure brain volumes. 2-wayANCOVA, co-varying for education, depressive symptoms, and intracranial volume, evaluated for independent and interactive effects of group status and sex. Abnormal brain volumes were correlated with BIS. Results:METH users had higher impulsivity scores in all six factors (p<0.0001–0.006). All women had lower scores in attention compared to men (p=0.02). A group-by-sex interaction was found in perseverance (p=0.03); male METH users had higher scores compared to CON and female METH (p<0.0001–0.04). METH had larger right (R) globus pallidus (p=0.03) and R insula (p=0.01), but smaller left (L) insula (p=0.04). Only male METH had smaller L precentral gyrus than male CON (p=0.06), but only female METH had larger R accumbens than female CON (p=0.02). L precentral volumes negatively correlated with attention scores in females (r=−0.36, p=0.02), but not in the males (interaction-p=0.05). Conclusions: Consistent with prior reports, METH users had greater impulsivity, especially in the males. METH users also had larger R globus pallidus, but smaller L insula, andmale METH users tended to have smaller precentral gyrus. In women, those with larger precentral gyrushadbetter attention, similar to that inADHD patients.While larger accumbenswas also reported inMETHusers, we found this only in female METH users. The larger volume in femaleMETH usersmay be due to greater neuroinflammation than in men, which may reflect a compensatory neuroprotective effect in female METH users. Financial Support: R24DA-27318; K24DA-16170; U54NS56883; G12-MD007601.