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

Background: Data suggest that the amygdala and hippocampus contribute to cocaine seeking and use, particularly following exposure to cocaine-related cues and contexts. Furthermore, indices of pre-treatment cocaine-use severity have been shown to correlate with treatment outcome in cocaine-dependent patients.

Methods: The aim of this study was to assess the relationships between amygdalar and hippocampal volumes and cocaine use before and during treatment. High-resolution magnetic-resonance brain images were obtained from 23 cocaine-dependent patients prior to treatment and 54 healthy comparison individuals. Automated segmentation of the amygdala and hippocampus images was performed in FreeSurfer. Cocaine-dependent patients subsequently received behavioral therapy alone or combined with contingency management as part of a treatment trial, and cocaine-use indices (self-report, urine toxicology) were collected.

Results: Comparison participants and cocaine-dependent patients did not show significant difference in amygdalar and hippocampal volumes at pre-treatment. Within the patient group, greater hippocampal volumes were correlated with more days of cocaine use before treatment and with poorer treatment outcome as indexed by shorter durations of continuous abstinence from cocaine and lower percentages of cocaine-negative urine samples during treatment. Mediation analysis indicated that pre-treatment hippocampal volumes mediated the relationships between pre-treatment cocaine use and treatment outcomes.

Conclusions: The finding of a significant correlation between hippocampal volume and pre-treatment cocaine-use severity and treatment response suggests that hippocampal volume should be considered when developing individualized treatments for cocaine dependence.