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

Abstract

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 pretreatment. 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.

Basal Hippocampal Activity and Its Functional Connectivity Predicts Cocaine Relapse

“…The absence of this structure/function association in both cocaine-dependent subgroups suggests disease-associated processes may be driving the differences in pHp neural activity. Further, in contrast to a recent report by Xu et al (61), we did not observe a difference in hippocampal volume between relapsed and early remission individuals.…”

Biomarkers for Success

“…The same group was able to replicate these predictive findings in an independent sample using the seed derived from their initial study and a measure of cerebral blood flow done with Single-photon emission computed tomography (SPECT, rather than pCASL) (Adinoff, Harris, Gu, & Stein, 2016). This proposed hippocampal hyperactivity supports other work in which hippocampal volume was positively associated with a return to drug use (Xu et al, 2014). …”

“…For instance, increased amygdala activation in response to implicit cocaine cues correlated with positive affective response ratings to the cues—demonstrating its importance in identification of salience of drug-related stimuli even outside of awareness. (Childress et al, 2008) Amygdala volume has been reported as smaller among cocaine-dependent people compared to controls (Makris et al, 2004) however more recent studies with larger sample sizes have found divergent results (Mei, Xu, Carroll, & Potenza, 2015; Xu et al, 2014). Despite no significant differences in volume, Mei et al did find a negative relationship in cocaine users between amygdala volume and measures of impulsivity (Mei et al, 2015).…”

“…Extensive preclinical work has shown that the hippocampus, along with the amygdala, are involved in stress and cocaine cue induced reinstatement (Atkins, Mashhoon, & Kantak, 2008; Belujon & Grace, 2011; Fuchs, Eaddy, Su, & Bell, 2007; Fuchs et al, 2005; Rogers & See, 2007; See, 2005). Unlike the prefrontal cortex, the hippocampus is not typically smaller in cocaine users than controls (Makris et al, 2004; Mei et al, 2015; Xu et al, 2014), and one group has found that hippocampal volume in individuals entering treatment was prospectively associated with more drug use as measured by urine drug screens and self-report (Xu et al, 2014). Additionally, there is greater cerebral metabolism in the right hippocampus when individuals view cocaine videos compared to neutral videos (Fotros et al, 2013).…”

Anticipatory reward processing among cocaine-dependent individuals with and without concurrent methadone-maintenance treatment: Relationship to treatment response

“…Neural structural factors within regions including the caudate and hippocapmus are related to treatment outcomes among individuals with addictions (Xu et al, 2014; Yip et al, 2014). In addition, individual variability in neurofunctional responses during MID task performance has been linked to neurostructural variability (Yip et al, 2015).…”