Gaudreault Pierre-Olivier, King Sarah G, Huang Yuefeng, Ceceli Ahmet O, Kronberg Greg, Alia-Klein Nelly, Goldstein Rita Z
Psychiatry and Neuroscience Departments, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
medRxiv. 2024 Jun 11:2024.06.10.24308719. doi: 10.1101/2024.06.10.24308719.
Amidst an unprecedented opioid epidemic, identifying neurobiological correlates of change with medication-assisted treatment of heroin use disorder is imperative. Distributed white matter (WM) impairments in individuals with heroin use disorder (iHUD) have been associated with increased drug craving, a reliable predictor of treatment outcomes. However, little is known about the extent of whole-brain structural connectivity changes with inpatient treatment and abstinence in iHUD.
To assess WM microstructure and associations with drug craving changes with inpatient treatment in iHUD (effects of time/re-scan compared to controls; CTL).
Longitudinal cohort study (12/2020-09/2022) where iHUD and CTL underwent baseline magnetic resonance imaging (MRI#1) and follow-up (MRI#2) scans, (mean interval of 13.9 weeks in all participants combined).
The iHUD and CTL were recruited from urban inpatient treatment facilities and surrounding communities, respectively.
Thirty-four iHUD (42.1yo; 7 women), 25 age-/sex-matched CTL (40.5yo; 9 women).
Between scans, inpatient iHUD continued their medically-assisted treatment and related clinical interventions. CTL participants were scanned at similar time intervals.
Changes in white matter diffusion metrics [fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivities (RD)] in addition to baseline and cue-induced drug craving, and other clinical outcome variables (mood, sleep, affect, perceived stress, and therapy attendance).
Main findings showed HUD-specific WM microstructure changes encompassing mostly frontal major callosal, projection, and association tracts, characterized by increased FA (.949<1-p<.986) and decreased MD (.949<1-p<.997) and RD (.949<1-p<.999). The increased FA (r=-0.72, p<.00001) and decreased MD (r=0.69, p<.00001) and RD (r=0.67, p<.0001) in the genu and body of the corpus callosum and the left anterior corona radiata in iHUD were correlated with a reduction in baseline craving (.949<1-p<.999). No other WM correlations with outcome variables reached significance.
Our findings suggest whole-brain normalization of structural connectivity with inpatient medically-assisted treatment in iHUD encompassing recovery in frontal WM pathways implicated in emotional regulation and top-down executive control. The association with decreases in baseline craving further supports the relevance of these WM markers to a major symptom in drug addiction, with implications for monitoring clinical outcomes.
在前所未有的阿片类药物流行背景下，确定海洛因使用障碍药物辅助治疗中变化的神经生物学相关性至关重要。海洛因使用障碍患者（iHUD）存在的分布式白质（WM）损伤与药物渴望增加有关，而药物渴望是治疗结果的可靠预测指标。然而，对于iHUD患者住院治疗及戒断后全脑结构连接变化的程度知之甚少。
评估iHUD患者住院治疗期间WM微观结构及其与药物渴望变化的关联（与对照组相比，时间/重新扫描的影响；CTL）。
纵向队列研究（2020年12月 - 2022年9月），iHUD组和CTL组接受了基线磁共振成像（MRI#1）和随访（MRI#2）扫描（所有参与者的平均间隔为13.9周）。
iHUD组和CTL组分别从城市住院治疗设施和周边社区招募。
34名iHUD患者（42.1岁；7名女性），25名年龄和性别匹配的CTL参与者（40.5岁；9名女性）。
在两次扫描之间，住院的iHUD患者继续接受药物辅助治疗及相关临床干预。CTL参与者在相似的时间间隔进行扫描。
白质扩散指标的变化[分数各向异性（FA）、平均扩散率（MD）、轴向扩散率（AD）和径向扩散率（RD）]，以及基线和线索诱导的药物渴望，和其他临床结局变量（情绪、睡眠、情感、感知压力和治疗出勤率）。
主要研究结果显示，特定于HUD的WM微观结构变化主要涉及额叶主要胼胝体、投射和联合束，其特征为FA增加（.949 < 1 - p <.986）、MD降低（.949 < 1 - p <.997）和RD降低（.949 < ！ - p <.999）。iHUD患者胼胝体膝部和体部以及左侧前放射冠中FA增加（r = - 0.72，p <.00001）、MD降低（r = 0.69，p <.00001）和RD降低（r = 0.67，p <.0001）与基线渴望降低相关（.949 < 1 - p <.999）。没有其他WM与结局变量的相关性达到显著水平。
我们的研究结果表明，iHUD患者住院药物辅助治疗后全脑结构连接正常化，包括涉及情绪调节和自上而下执行控制的额叶WM通路的恢复。与基线渴望降低的关联进一步支持了这些WM标记物与药物成瘾主要症状的相关性，对监测临床结局具有重要意义。
