南京医科大学Fei Wang等研究人员合作揭示早发精神障碍中的海马发育异常和干预措施。相关论文于2023年12月23日在线发表在《神经科学快报》杂志上。

研究人员对甲基偶氮氧乙酸甲酯（MAM）大鼠的幼年期、青春期和成年期进行了纵向结构磁共振成像（MRI）扫描，以确定特定的脑区和干预的关键窗口。然后，研究人员揭示了在关键窗口期对目标脑区进行重复经颅磁刺激（rTMS）干预的效果。此外，研究人员还在一组患有早发精神障碍（被诊断为重度抑郁症或双相情感障碍）的青少年患者身上测试了这一干预范式的疗效，以评估其临床转化潜力。结果表明，与对照组相比，MAM大鼠从幼年期到成年期的纹状体体积都明显较低（P均小于0.001）。相比之下，海马体的体积在儿童期并无显著差异（P>0.05），但从青春期到成年期则明显低于对照组（P均<0.001）。

随后，对MAM模型的枕叶皮层进行经颅磁刺激，该皮层在解剖学上与海马相连。与MAM-sham组相比，MAM-rTMS组的海马体积显著增加（P<0.01），而纹状体的体积保持不变（P>0.05）。在临床试验中，与基线相比，经颅磁刺激治疗后，患有早发精神障碍的青少年的海马体积显著增加（P<0.01），这些体积变化与抑郁症状的改善相关（r=-0.524，P=0.018）。这些研究结果凸显了针对青春期海马发育异常进行干预的潜力，以及经颅磁刺激作为缓解神经发育异常过程和减轻临床症状的治疗方法的前景。

据了解，早发性精神障碍与青春期神经发育过程紊乱有关。MAM动物模型会诱发神经发育过程的紊乱，从病因学的角度模拟了与早发性精神障碍相关的神经发育异常。

附：英文原文

Title: Aberrant Hippocampal Development in Early-onset Mental Disorders and Promising Interventions: Evidence from a Translational Study

Author: Yang, Jingyu, Guo, Huiling, Cai, Aoling, Zheng, Junjie, Liu, Juan, Xiao, Yao, Ren, Sihua, Sun, Dandan, Duan, Jia, Zhao, Tongtong, Tang, Jingwei, Zhang, Xizhe, Zhu, Rongxin, Wang, Jie, Wang, Fei

Issue&Volume: 2023-12-23

Abstract: Early-onset mental disorders are associated with disrupted neurodevelopmental processes during adolescence. The methylazoxymethanol acetate (MAM) animal model, in which disruption in neurodevelopmental processes is induced, mimics the abnormal neurodevelopment associated with early-onset mental disorders from an etiological perspective. We conducted longitudinal structural magnetic resonance imaging (MRI) scans during childhood, adolescence, and adulthood in MAM rats to identify specific brain regions and critical windows for intervention. Then, the effect of repetitive transcranial magnetic stimulation (rTMS) intervention on the target brain region during the critical window was investigated. In addition, the efficacy of this intervention paradigm was tested in a group of adolescent patients with early-onset mental disorders (diagnosed with major depressive disorder or bipolar disorder) to evaluate its clinical translational potential. The results demonstrated that, compared to the control group, the MAM rats exhibited significantly lower striatal volume from childhood to adulthood (all P &lt;0.001). In contrast, the volume of the hippocampus did not show significant differences during childhood (P &gt;0.05) but was significantly lower than the control group from adolescence to adulthood (both P &lt;0.001). Subsequently, rTMS was applied to the occipital cortex, which is anatomically connected to the hippocampus, in the MAM models during adolescence. The MAM-rTMS group showed a significant increase in hippocampal volume compared to the MAM-sham group (P &lt;0.01), while the volume of the striatum remained unchanged (P &gt;0.05). In the clinical trial, adolescents with early-onset mental disorders showed a significant increase in hippocampal volume after rTMS treatment compared to baseline (P &lt;0.01), and these volumetric changes were associated with improvement in depressive symptoms (r = −&nbsp;0.524, P = 0.018). These findings highlight the potential of targeting aberrant hippocampal development during adolescence as a viable intervention for early-onset mental disorders with neurodevelopmental etiology as well as the promise of rTMS as a therapeutic approach for mitigating aberrant neurodevelopmental processes and alleviating clinical symptoms.

DOI: 10.1007/s12264-023-01162-2

Source: https://link.springer.com/article/10.1007/s12264-023-01162-2