Relationship Between Synaptic Density and Cortical (Micro)structure in Healthy Participants, Patients With Schizophrenia Spectrum Disorder, and Unaffected Siblings: A Multimodal [11C]UCB-J Positron Emission Tomography and Magnetic Resonance Imaging Study

IF 4.9 2区医学 Q1 NEUROSCIENCES

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging Pub Date : 2026-10-01 Epub Date: 2025-11-29 DOI:10.1016/j.bpsc.2025.11.008

Jesca E. de Jager, Monique van der Weijden-Germann, Edwin van Dellen, Erik F.J. de Vries, Iris E.C. Sommer, Jasper O. Nuninga

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引用次数: 0

Abstract

Background

The structure and tissue composition of the cortex may be sensitive to loss of synapses. However, the relationship between measurements of synaptic density, cortical thickness, and microstructure remains unknown. These measures are reduced in schizophrenia spectrum disorders (SSDs) and to a lesser degree in unaffected relatives. Here, we investigated whether synaptic density and cortical (micro)structure are related in healthy participants and whether these associations are altered in patients with SSDs and unaffected siblings.

Methods

Brain uptake of the tracer [¹¹C]UCB-J, measured in vivo with positron emission tomography (PET), was used as a proxy measure for synaptic density. Healthy participants (n = 25), patients with SSDs (n = 24), and unaffected siblings (n = 25) underwent [¹¹C]UCB-J PET, T1-weighted magnetic resonance imaging, and diffusion-weighted imaging scans.

Results

We found a positive relationship between [¹¹C]UCB-J nondisplaceable binding potential (BP_ND) and cortical thickness (β = 0.61, p = .02) and showed a similar (although nonsignificant) positive relationship in unaffected siblings (β = 0.41, p = .09). This relationship was not present in patients with SSDs (β = 0.03, p = .90). Additionally, [¹¹C]UCB-J BP_ND had a negative relationship with mean diffusivity in control participants (β = −0.54, p = .01) and unaffected siblings (β = −0.47, p = .01). In patients with SSDs, again this relationship was disrupted (β = 0.07, p = .78).

Conclusions

We found a robust association between synaptic density and cortical (micro)structure in healthy individuals. The lost relationship in patients suggests that SSD-related synapse loss is not proportional to the number and organization of gray matter constituents. Despite the shared genetic risk, this relationship is preserved in unaffected siblings, suggesting the absence of a “second hit” inducing excessive synaptic pruning.

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健康受试者、精神分裂症谱系障碍患者和未患病兄弟姐妹突触密度与皮质（微观）结构的关系：一项多模态[11C]UCB-J PET和MRI研究

背景：皮层的结构和组织组成可能对突触的丧失很敏感。然而，突触密度、皮质厚度和微观结构之间的关系尚不清楚。这些措施在精神分裂症谱系障碍（SSD）中减少，在未受影响的亲属中减少程度较小。在这里，我们研究了健康受试者的突触密度和皮层（微观）结构是否相关，以及这些关联在SSD患者和未患病的兄弟姐妹中是否改变。方法：采用活体正电子发射断层扫描（PET）测量示踪剂[11C]UCB-J的脑摄取作为突触密度的替代测量。健康受试者（n=25）、SSD患者（n=24）和未受影响的兄弟姐妹（n=25）接受了[11C]UCB-J PET、t1加权MRI和扩散加权成像扫描。结果：我们发现[11C]UCB-J BPND与皮质厚度呈正相关（β=0.61, p= 0.02），在未受影响的兄弟姐妹中也表现出类似（但不显著）的正相关（β=0.41, p= 0.09）。这种关系在SSD患者中不存在（β=0.03, p= 0.90）。此外，[11C]UCB-J BPND与对照组（β=-0.54, p= 0.01）和未患病兄弟姐妹（β=-0.47, p= 0.01）的平均扩散率（MD）呈负相关。在SSD患者中，这种关系再次被打破（β=0.07, p= 0.78）。结论：我们发现健康个体的突触密度与皮层（微观）结构之间存在密切关联。患者的丢失关系表明，ssd相关的突触丢失与灰质成分的数量和组织不成比例。尽管有共同的遗传风险，但未受影响的兄弟姐妹保持了这种关系，这表明没有第二次打击导致过度的突触修剪。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biological Psychiatry-Cognitive Neuroscience and Neuroimaging Neuroscience-Biological Psychiatry

CiteScore

10.40

自引率

1.70%

发文量

247

审稿时长

30 days

期刊介绍： Biological Psychiatry: Cognitive Neuroscience and Neuroimaging is an official journal of the Society for Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal focuses on studies using the tools and constructs of cognitive neuroscience, including the full range of non-invasive neuroimaging and human extra- and intracranial physiological recording methodologies. It publishes both basic and clinical studies, including those that incorporate genetic data, pharmacological challenges, and computational modeling approaches. The journal publishes novel results of original research which represent an important new lead or significant impact on the field. Reviews and commentaries that focus on topics of current research and interest are also encouraged.