绘制精神病患者灰质改变的分子和微观结构图

IF 9.6 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Psychiatry Pub Date : 2024-09-12 DOI:10.1038/s41380-024-02724-0
Natalia García-San-Martín, Richard A. I. Bethlehem, Agoston Mihalik, Jakob Seidlitz, Isaac Sebenius, Claudio Alemán-Morillo, Lena Dorfschmidt, Golia Shafiei, Víctor Ortiz-García de la Foz, Kate Merritt, Anthony David, Sarah E. Morgan, Miguel Ruiz-Veguilla, Rosa Ayesa-Arriola, Javier Vázquez-Bourgon, Aaron Alexander-Bloch, Bratislav Misic, Edward T. Bullmore, John Suckling, Benedicto Crespo-Facorro, Rafael Romero-García
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引用次数: 0

摘要

精神病谱包含一系列与大脑发育异常有关的不同临床症状。要检测各种精神疾病的非典型神经解剖学成熟模式,需要一种可解释的衡量标准,并根据年龄、性别和部位效应进行标准化。导致大脑结构偏离典型神经发育模式的分子和微观结构属性尚不清楚。在这里,我们汇总了来自 38696 名健康对照组(HC)和 1256 名精神病相关病例的结构磁共振成像数据,包括精神分裂症(SCZ)和情感分裂症(SAD)患者的一级亲属(n = 160)、有精神病经历的人(n = 157)、精神病首次发作患者(FEP,n = 352)以及慢性 SCZ 或 SAD 患者(n = 587)。我们使用规范建模方法生成了皮质灰质(GM)表型的百分位数,确定了所有情况下区域体积低于预期轨迹的偏差,其中临床诊断的 FEP 和慢性患者受到的影响更大。此外,我们还采用多元方法将健康人的 46 种神经生物学特征(包括神经递质、细胞类型、层厚度、微结构、皮质扩展和新陈代谢)映射到这些异常中心。结果发现,神经生物学特征与中心偏离高度共定位,其中新陈代谢(如脑氧代谢率(CMRGlu)和脑血流量(CBF))和神经递质浓度(如血清素(5-HT)和乙酰胆碱(α4β2)受体)与异常基因组轨迹的空间重叠最为一致。综上所述,这些发现揭示了在精神病的不同阶段可能导致大脑非典型成熟的易感因素。
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Molecular and micro-architectural mapping of gray matter alterations in psychosis

The psychosis spectrum encompasses a heterogeneous range of clinical conditions associated with abnormal brain development. Detecting patterns of atypical neuroanatomical maturation across psychiatric disorders requires an interpretable metric standardized by age-, sex- and site-effect. The molecular and micro-architectural attributes that account for these deviations in brain structure from typical neurodevelopment are still unknown. Here, we aggregate structural magnetic resonance imaging data from 38,696 healthy controls (HC) and 1256 psychosis-related conditions, including first-degree relatives of schizophrenia (SCZ) and schizoaffective disorder (SAD) patients (n = 160), individuals who had psychotic experiences (n = 157), patients who experienced a first episode of psychosis (FEP, n = 352), and individuals with chronic SCZ or SAD (n = 587). Using a normative modeling approach, we generated centile scores for cortical gray matter (GM) phenotypes, identifying deviations in regional volumes below the expected trajectory for all conditions, with a greater impact on the clinically diagnosed ones, FEP and chronic. Additionally, we mapped 46 neurobiological features from healthy individuals (including neurotransmitters, cell types, layer thickness, microstructure, cortical expansion, and metabolism) to these abnormal centiles using a multivariate approach. Results revealed that neurobiological features were highly co-localized with centile deviations, where metabolism (e.g., cerebral metabolic rate of oxygen (CMRGlu) and cerebral blood flow (CBF)) and neurotransmitter concentrations (e.g., serotonin (5-HT) and acetylcholine (α4β2) receptors) showed the most consistent spatial overlap with abnormal GM trajectories. Taken together these findings shed light on the vulnerability factors that may underlie atypical brain maturation during different stages of psychosis.

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来源期刊
Molecular Psychiatry
Molecular Psychiatry 医学-精神病学
CiteScore
20.50
自引率
4.50%
发文量
459
审稿时长
4-8 weeks
期刊介绍: Molecular Psychiatry focuses on publishing research that aims to uncover the biological mechanisms behind psychiatric disorders and their treatment. The journal emphasizes studies that bridge pre-clinical and clinical research, covering cellular, molecular, integrative, clinical, imaging, and psychopharmacology levels.
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