Abstract
Methadone maintenance treatment (MMT) has elevated rates of co-morbid memory deficit and depression that are associated with higher relapse rates for substance abuse. White matter (WM) disruption in MMT patients have been reported but their impact on these co-morbidities is unknown. This study aimed to investigate changes in WM integrity of MMT subjects using diffusion tensor image (DTI), and their relationship with history of heroin and methadone use in treated opiate-dependent individuals. The association between WM integrity changes from direct group comparisons and the severity of memory deficit and depression was also investigated. Differences in WM integrity between 35 MMT patients and 23 healthy controls were evaluated using DTI with tract-based spatial statistical analysis. Differences in DTI indices correlated with diminished memory function, Beck Depression Inventory, duration of heroin use and MMT, and dose of heroin and methadone administration. Changes in WM integrity were found in several WM regions, including the temporal and frontal lobes, pons, cerebellum, and cingulum bundles. The duration of MMT was associated with declining DTI indices in the superior longitudinal fasciculus and para-hippocampus. MMT patients had more memory and emotional deficits than healthy subjects. Worse scores in both depression and memory functions were associated with altered WM integrity in the superior longitudinal fasciculus, para-hippocampus, and middle cerebellar peduncle in MMT. Patients on MMT also had significant WM differences in the reward circuit and in depression- and memory-associated regions. Correlations among decreased DTI indices, disease severity, and accumulation effects of methadone suggest that WM alterations may be involved in the psychopathology and pathophysiology of co-morbidities in MMT.
Highlights
Methadone hydrochloride is proven advantageous as treatment for heroin dependence [1]
Increasing the understanding of the neural basis and the associated cognitive functioning that occurs in chronic heroin use, especially in methadone maintenance therapy (MMT), may help design better treatment strategies
Maladaptive memories associated with drug abuse may result in relapse to drug-seeking and drug-taking behavior
Summary
Methadone hydrochloride is proven advantageous as treatment for heroin dependence [1]. Despite its extensive therapeutic applications, as maintenance treatment it has prominent adverse effects on several cognitive functions, including different levels-ofprocessing framework of psychological memory dysfunction and depression symptoms, which in turn contribute to poorer prognosis and quality of life [2,3,4]. Increasing the understanding of the neural basis and the associated cognitive functioning that occurs in chronic heroin use, especially in methadone maintenance therapy (MMT), may help design better treatment strategies. Heroin-dependent individuals have depression that far exceeds estimates for the general population, have elevated suicide risk [7], and are associated with higher rates of drug re-use [8]. A clear mechanism between drugs abuse, altered memories, emotion, and the corresponding neuroanatomy remains unknown
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