Striatal resting-state connectivity after long-term diacetylmorphine treatment in opioid-dependent patients

Abstract

New treatment approaches for opioid-dependent patients include injectable opioid agonist treatment with diacetylmorphine. While evidence has shown beneficial clinical effects of diacetylmorphine, it is still not clear how long-term diacetylmorphine treatment affects the brain and whether functional brain changes are accompanied by clinical improvements. Therefore, this prospective case-control study focuses on long-term effects of diacetylmorphine on resting-state functional connectivity. We included opioid-dependent patients (N = 22, age range 33-58, 16 males) treated with diacetylmorphine and healthy controls (N = 9, age range 27-55, 5 males) that underwent two MRI assessments approximately nine years apart. For the patients, the assessments took part shortly after the diacetylmorphine intake to be able to explore changes in resting-state functional connectivity in brain regions related to the stage of binge and intoxication (caudate, putamen, nucleus accumbens). A cluster in the right superior frontal gyrus was detected, showing over nine years an increase in functional connectivity originating from the left caudate and the left accumbens in patients but not in healthy controls. These connectivity changes in patients were related to the duration of the diacetylmorphine treatment at the follow-up, indicating smaller increases in functional connectivity with longer treatment duration (r = 0.63, P < 0.01). These results suggest that long-term diacetylmorphine treatment in opioid-dependent patients increases fronto-striatal connections, an effect that is linked to the duration of the treatment duration. Future research needs to further address the wide-ranging effects of diacetylmorphine on brain functioning and deepen the understanding of their clinical relevance.

Keywords: diacetylmorphine; heroin maintenance; long-term effects; resting-state functional MRI; striatum.

Graphical abstract

Figure 1 Seed regions of seed-to-voxel analysis for binge/intoxication stage.

Binge regions consisted of the bilateral caudate, putamen and nucleus accumbens according to the Harvard-Oxford subcortical structural atlas as implemented in conn.

Figure 2 Resting-state functional connectivity (rsFC) from binge/intoxication regions to the right superior frontal gyrus (SFG).

(A) Location of the cluster in right SFG (x = +10, y = +10, z = +60). Significant posthoc tests in rsFC from (B) left caudate (T(29) = 4.88, P < 0.001) with (C) individual trajectories and (D) left nucleus accumbens (NA) (T(29) = 6.69, P < 0.001) with (E) corresponding individual trajectories.

Figure 3 Significant positive correlation (r = 0.63, P < 0.01) between resting-state functional connectivity (rsFC) changes in left nucleus accumbens (NA) to right superior frontal gyrus (SFG) and duration of DAM treatment (in years) in patients.