Methadone-induced Damage to White Matter Integrity in Methadone Maintenance Patients: A Longitudinal Self-control DTI Study

Abstract

Methadone maintenance treatment (MMT) can induce impairments in brain function and structure, despite its clinical effectiveness. However, the effect of chronic MMT on brain white matter (WM) is not fully known. Thirty-three MMT patients underwent diffusion tensor imaging (DTI) twice - at the start of the study (Scan1) and one year later (Scan2). Tract-based spatial statistics were used to investigate changes in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) between the two scans. The correlations between DTI indices and methadone consumption and neuropsychological status were analysed. We found significantly decreased FA, decreased AD and increased RD in Scan2 in extensive WM regions; overlapping regions were found in the left posterior limb and the retrolenticular part of internal capsule, superior and posterior corona radiata, bilateral external capsule and the right superior longitudinal fasciculus. In addition, the change of FA in the overlapping regions was positively correlated with the accumulated dosage of methadone use, the RD value in Scan2 and non-planning impulsiveness (NPI) measured at follow-up. The results suggest that methadone has damaging effects on WM integrity. The dose-dependent pattern and characteristics of the impairment may suggest new strategies for MMT.

Figure 1. TBSS analysis of FA, AD and RD between S₂ and S₁.

Compared with S₁, S₂ showed significantly decreased FA (a), decreased AD (b) and increased RD (c) in extensive white matter regions (P < 0.05, corrected by TFCE and FWE). S₁ and S₂ are Scan₁ and Scan₂, respectively.

Figure 2. Overlapping white matter regions with changes in FA, AD and RD.

White matter regions with decreased FA, decreased AD and increased RD are shown in red (a). Regions with decreased FA and decreased AD are shown in yellow (b). Regions with decreased FA and increased RD are shown in purple (c).

Figure 3. Correlations between DTI indices and clinical characteristics.

The proportion of change in FA in the overlapping regions was positively correlated with the accumulated dosage of methadone use within one year (a). The RD value in the overlapping regions in S₂ were positively correlated with the NPI score measured at follow-up (b). RD values × 10⁻³ mm²/s. S₂ is Scan₂.