Social and Cognitive Computing Department, Institute of High Performance Computing, Agency for Science, Technology and Research, Singapore, Singapore.
Division of Population and Behavioral Science, Medical School, University of St Andrews, St Andrews, UK.
Transl Psychiatry. 2022 Feb 26;12(1):81. doi: 10.1038/s41398-022-01813-4.
Opioid use disorder (OUD) affects more than 27 million people globally accounting for more than 300,000 deaths annually. Protracted abstinence among individuals with OUD is rare due to a high relapse rate among those not receiving medications for OUD. Extensive preclinical studies form the basis of the allostasis theory, which proposes long-lasting functional brain abnormalities that persist after opioid withdrawal and contribute to relapse. Few studies have tested the allostasis theory in humans using neuroimaging. Here, we used fMRI and an instrumental learning task to test allostasis theory predictions (ATP) of functional abnormalities in both positive valence (PVS) and negative valence (NVS) accumbens systems in OUD patients with protracted abstinence (n = 15), comparing them with OUD patients receiving methadone treatment (MT) (n = 33), and with healthy controls (n = 23). As hypothesized, protracted abstinence OUD patients showed incomplete recovery of nucleus accumbens function, as evidenced by the blunted response to aversive events (NVS) during negative reinforcement, as observed in MT patients. In contrast, their accumbens response to rewarding events (PVS) during positive reinforcement was similar to that of controls and different from that in MT patients whose response was blunted. Protracted abstinence OUD patients also showed improvements in depression symptoms compared to MT patients. Residual depressive symptoms and pre-MT intravenous drug measures were associated with worse accumbens function in protracted abstinence. These results support the ATP of long-lasting dysfunction of NVS after withdrawal and show preliminary evidence of recovery of PVS function with protracted withdrawal. Therapeutic strategies that target NVS may facilitate recovery.
阿片类使用障碍（OUD）影响着全球超过 2700 万人，每年导致超过 30 万人死亡。由于未接受 OUD 治疗的患者复发率很高，因此，OUD 患者的长期禁欲很少见。广泛的临床前研究构成了适应理论的基础，该理论提出了在阿片类药物戒断后持续存在的持久的大脑功能异常，这导致了复发。很少有研究使用神经影像学在人类中测试适应理论。在这里，我们使用 fMRI 和一项仪器学习任务来测试 OUD 患者（n=15，有长期禁欲）和接受美沙酮治疗的 OUD 患者（n=33）以及健康对照组（n=23）的正价（PVS）和负价（NVS）伏隔核系统中功能异常的适应理论预测（ATP）。正如假设的那样，长期禁欲的 OUD 患者的伏隔核功能恢复不完全，这表现为在负强化期间对厌恶事件（NVS）的反应迟钝，这在接受美沙酮治疗的患者中观察到。相比之下，他们在正强化期间对奖励事件（PVS）的伏隔核反应与对照组相似，与美沙酮治疗患者的反应不同，后者的反应迟钝。与接受美沙酮治疗的患者相比，长期禁欲的 OUD 患者的抑郁症状也有所改善。残留的抑郁症状和接受美沙酮治疗前的静脉药物使用情况与长期禁欲时伏隔核功能较差有关。这些结果支持 NVS 长期功能障碍的 ATP，并初步证明了长期禁欲时 PVS 功能的恢复。针对 NVS 的治疗策略可能有助于恢复。
