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Plasma proteomics and related pathways of OCD

Poster No:

518

Submission Type:

Abstract Submission

Authors:

Shujie Geng¹, LiPing Zheng¹, Linbo Wang¹, Trevor Robbins², JianFeng Feng¹

Institutions:

¹Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China, ²University of Cambridge, Cambridge, UK

First Author:

Shujie Geng
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China

Co-Author(s):

LiPing Zheng
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China

Linbo Wang
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China

Trevor Robbins
University of Cambridge
Cambridge, UK

JianFeng Feng
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University
Shanghai, China

Introduction:

Obsessive-compulsive disorder (OCD) is a relatively common neuropsychiatric disorder characterizing by compulsivity, repetitive and unwanted thoughts and behaviors, and potential maladaptive consequences. The frontal-striatal model underlying goal-directed and habitual systems has uncovered the neural mechanism of pathophysiology of OCD and supported by reasonable neuroimaging, neurotransmitter and animal studies [1]. However, the comprehensive perspective of peripheral mechanism underlying OCD is still largely unknown. As the final products of gene expression, protein is of great importance in various cellular functions and can reflect dynamic external and internal changes. Also, blood is relatively easy to access in clinical. It indicates that plasma proteins and its associations with gene and brain might be of huge potential to serve as the biomarker and provide new insights into the pathophysiology of OCD. Despite the potential of plasma proteins for OCD, previous studies showed inconsistent findings due to the small sample sizes, limited proteomic coverage and association with multiscale measurements. The recent released plasma proteomics data from UK Biobank Pharma Proteomics Project (UKB-PPP) makes it possible to bridge the gap.

Methods:

The 2,920 plasma proteins across 53,026 participants from UKB-PPP was used to identify the OCD-related proteins and their pathways. 93 OCD patients were diagnosed according to the ICD-10 codes in Data-Field 41270, excluding blood and immune disorders, endocrine disorders, mental and behavioral disorders, and nervous system disorders. 886 healthy controls were matched according to age, sex, ethnic, education, townsend and BMI. To identify the OCD-related plasma proteins, two sample t test and FDR correction was utilized between OCD patients and healthy controls across proteins. To evaluate the biological relevance of the identified OCD-related proteins, we conducted functional enrichment analysis for Geno Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The associations between OCD-related proteins and brain structural measurements were calculated in healthy populations with the Bonferroni correction. To further identify the casual relationship between the identified plasma proteins and OCD, two sample Mendelian Randomization and FDR correction were conducted. The temporal progress of the casual plasma proteins was illustrated.

Results:

By two sample t test and FDR correction (p < 0.05), 47 plasma proteins showed significantly different expression levels between OCD populations and healthy controls as shown in Figure 1.A. 41 proteins were hyper-expressed with the GAST, GDF15 and CXCL17 as the top 3. The functional enrichment analysis in Figure 1.B showed that the OCD-related protein was functionally associated with immune response including macrophage migration and leukocyte activation. 7 OCD-related proteins (CXCL17, GDF15, HAVCR1, ACE2, WFDC2, AMBP and OGN) were significantly associated with brain volumes in bilateral inferior temporal gyrus, left middle temporal gyrus, bilateral thalamus and right accumbens after Bonferroni corrected (p < 0.05). The two sample Mendelian Randomization identified 3 proteins (ANXA10, TREM2 and GDF15) casually related to the outcome of OCD. Inversed U-shape trajectory was observed in GDF15, while TREM2 gradually decreased.

Conclusions:

47 OCD-related plasma proteins were identified and functionally annotated. Our results highlight the immune-related pathways and associations with brain structure in OCD.

Disorders of the Nervous System:

Psychiatric (eg. Depression, Anxiety, Schizophrenia) ¹

Modeling and Analysis Methods:

Other Methods

Novel Imaging Acquisition Methods:

Anatomical MRI ²

Keywords:

MRI

Obessive Compulsive Disorder

Psychiatric Disorders

^1|2Indicates the priority used for review

Abstract Information

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Healthy subjects only or patients (note that patient studies may also involve healthy subjects):

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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel? NOTE: Any human subjects studies without IRB approval will be automatically rejected.

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Were any animal research approved by the relevant IACUC or other animal research panel? NOTE: Any animal studies without IACUC approval will be automatically rejected.

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Please indicate which methods were used in your research:

Structural MRI

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Other, Please specify - Blood test

For human MRI, what field strength scanner do you use?

3.0T

Provide references using APA citation style.

[1] Robbins, T. W., Banca, P., & Belin, D. (2024). From compulsivity to compulsion: the neural basis of compulsive disorders. Nature reviews. Neuroscience, 25(5), 313–333.

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