Department of Psychiatry and Behavioral Health, Renaissance School Of Medicine at Stony Brook University, Stony Brook, New York, USA.
Department of Psychology, Program in Public Health, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
J Neuroendocrinol. 2023 Jul;35(7):e13316. doi: 10.1111/jne.13316. Epub 2023 Jul 25.
Opioid-induced deficits in maternal behaviors are well-characterized in rodent models. Amid the current epidemic of opioid use disorder (OUD), prevalence among pregnant women has risen sharply. Yet, the roles of buprenorphine replacement treatment for OUD (BT/OUD) in the brain functions of postpartum mothers are unclear. Using functional magnetic resonance imaging (fMRI), we have developed an evolutionarily conserved maternal behavior neurocircuit (MBN) model to study human maternal care versus defensive/aggressive behaviors critical to mother-child bonding. The anterior cingulate gyrus (ACC) is not only involved in the MBN for mother-child bonding and attachment, but also part of an opioid sensitive "pain-matrix". The literature suggests that prescription opioids produce physical and emotional "analgesic" effects by disrupting specific resting-state functional connectivity (rs-FC) of ACC to regions related to MBN. Thus, in this longitudinal study, we report findings of overlapping MBN and pain matrix circuits, for mothers with chronic exposure of BT/OUD. A total of 32 mothers were studied with 6 min rs-FC at 1 month (T1) and 4 months postpartum (T2), including seven on BT/OUD and 25 non-BT/OUD mothers as a comparison group. We analyzed rs-FC between the insula, putamen, and the dorsal anterior cingulate cortex (DACC) and rostral ACC (RACC), as the regions of interest that mediate opioid analgesia. BT/OUD mothers, as compared to non-BT/OUD mothers, showed less left insula-RACC rs-FC but greater right putamen-DACC rs-FC at T1, with these between-group differences diminished at T2. Some of these rs-FC results were correlated with the scores of postpartum parental bonding questionnaire. We found time-by-treatment interaction effects on DACC and RACC-dependent rs-FC, potentially identifying brain mechanisms for beneficial effects of BT, normalizing dysfunction of maternal brain and behavior over the first four months postpartum. This study complements recent studies to ascertain how BT/OUD affects maternal behaviors, mother-child bonding, and intersubjectivity and reveals potential MBN/pain-matrix targets for novel interventions.
阿片类药物诱导的母性行为缺陷在啮齿动物模型中得到了很好的描述。在当前阿片类药物使用障碍（OUD）流行的情况下，孕妇的患病率急剧上升。然而，丁丙诺啡替代治疗 OUD（BT/OUD）在产后母亲大脑功能中的作用尚不清楚。我们使用功能磁共振成像（fMRI）开发了一个进化保守的母婴行为神经回路（MBN）模型，以研究人类母婴护理与对母婴结合至关重要的防御/攻击行为。前扣带皮层（ACC）不仅参与母婴结合和依恋的 MBN，还参与阿片类药物敏感的“疼痛矩阵”。文献表明，处方类阿片类药物通过破坏与 MBN 相关的 ACC 与区域的特定静息状态功能连接（rs-FC），产生身体和情绪上的“镇痛”作用。因此，在这项纵向研究中，我们报告了慢性暴露于 BT/OUD 的母亲的重叠 MBN 和疼痛矩阵回路的发现。共有 32 名母亲参与了研究，她们在产后 1 个月（T1）和 4 个月（T2）时进行了 6 分钟 rs-FC，包括 7 名接受 BT/OUD 治疗的母亲和 25 名未接受 BT/OUD 治疗的母亲作为对照组。我们分析了岛叶、壳核和背侧前扣带皮层（DACC）与额前扣带皮层（RACC）之间的 rs-FC，作为介导阿片类药物镇痛的感兴趣区域。与非 BT/OUD 母亲相比，BT/OUD 母亲在 T1 时左岛叶-RACC 的 rs-FC 减少，但右壳核-DACC 的 rs-FC 增加，这种组间差异在 T2 时减小。这些 rs-FC 结果中的一些与产后父母纽带问卷的评分相关。我们发现 DACC 和 RACC 依赖的 rs-FC 存在时间-治疗相互作用效应，这可能确定了 BT 的有益效应的大脑机制，使产后 4 个月内母亲大脑和行为的功能障碍正常化。这项研究补充了最近的研究，以确定 BT/OUD 如何影响母婴行为、母婴结合和主体间性，并揭示了用于新型干预的潜在 MBN/疼痛矩阵靶点。
