Department of Psychiatry. Early Intervention Unit, Affiliated Nanjing Brain Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, PR China.
Department of Psychiatry and Gerontology, The First Affiliated Hospital, China Medical University, 155 Nanjing North Street, Shenyang, 110001, Liaoning, PR China.
BMC Psychiatry. 2023 Mar 9;23(1):153. doi: 10.1186/s12888-023-04597-z.
Schizophrenia (SZ) arises from a complex interplay involving genetic and molecular factors. Early intervention of SZ hinges upon understanding its vulnerability and resiliency factors in study of SZ and genetic high risk for SZ (GHR).
Herein, using integrative and multimodal strategies, we first performed a longitudinal study of neural function as measured by amplitude of low frequency function (ALFF) in 21 SZ, 26 GHR, and 39 healthy controls to characterize neurodevelopmental trajectories of SZ and GHR. Then, we examined the relationship between polygenic risk score for SZ (SZ-PRS), lipid metabolism, and ALFF in 78 SZ, and 75 GHR in cross-sectional design to understand its genetic and molecular substrates.
Across time, SZ and GHR diverge in ALFF alterations of the left medial orbital frontal cortex (MOF). At baseline, both SZ and GHR had increased left MOF ALFF compared to HC (P < 0.05). At follow-up, increased ALFF persisted in SZ, yet normalized in GHR. Further, membrane genes and lipid species for cell membranes predicted left MOF ALFF in SZ; whereas in GHR, fatty acids best predicted and were negatively correlated (r = -0.302, P < 0.05) with left MOF.
Our findings implicate divergence in ALFF alteration in left MOF between SZ and GHR with disease progression, reflecting vulnerability and resiliency to SZ. They also indicate different influences of membrane genes and lipid metabolism on left MOF ALFF in SZ and GHR, which have important implications for understanding mechanisms underlying vulnerability and resiliency in SZ and contribute to translational efforts for early intervention.
精神分裂症（SZ）是由遗传和分子因素复杂相互作用引起的。SZ 的早期干预取决于对 SZ 易感性和弹性因素以及 SZ 遗传高风险（GHR）的研究。
在此，我们首先使用整合和多模态策略，对 21 名 SZ、26 名 GHR 和 39 名健康对照者进行了神经功能的纵向研究，以衡量低频振幅（ALFF），以描述 SZ 和 GHR 的神经发育轨迹。然后，我们在横断面设计中检查了 SZ 的多基因风险评分（SZ-PRS）、脂质代谢与 ALFF 之间的关系，以了解其遗传和分子基础。
随着时间的推移，SZ 和 GHR 在左侧内侧眶额皮层（MOF）的 ALFF 改变上出现分歧。在基线时，与 HC 相比，SZ 和 GHR 的左侧 MOF ALFF 均增加（P < 0.05）。在随访时，SZ 的 ALFF 持续增加，但 GHR 则恢复正常。此外，细胞膜基因和细胞膜脂质种类可预测 SZ 的左侧 MOF ALFF；而在 GHR 中，脂肪酸是最佳预测指标，且与左侧 MOF 呈负相关（r = -0.302，P < 0.05）。
我们的发现表明，随着疾病的进展，SZ 和 GHR 之间左侧 MOF 的 ALFF 改变存在分歧，反映了 SZ 的易感性和弹性。它们还表明，在 SZ 和 GHR 中，细胞膜基因和脂质代谢对左侧 MOF ALFF 的影响不同，这对理解 SZ 易感性和弹性的机制具有重要意义，并为早期干预的转化努力做出了贡献。
