Dataset Information

Human brain prefrontal cortex proteomics identifies compromised energy metabolism and neuronal function in Schizophrenia

ABSTRACT: Understanding the pathophysiological substrates of schizophrenia is a major challenge for current neuropsychiatric research. As part of a set of multi-omics experiments, we performed an extensive case-control proteomics study on 192 post-mortem tissue sections from prefrontal cortex from 96 individuals, including 47 cases with schizophrenia and 49 healthy controls. Using two independently measured cortical datasets, we identified 387 proteins differentially expressed between schizophrenia cases and controls at a 5% FDR threshold. This significantly regulated set of proteins contains genes located in GWAS-identified schizophrenia loci and proteins identified by pQTL analysis. Gene ontology analysis using GOAT provided evidence for regulation of several major protein categories, emphasizing downregulation of mitochondrial oxidative respiration, ribosomes and the proteasome, upregulation of kinases and (small) GTPases. SynGO analysis supports the notion of synaptic dysfunction in schizophrenia, with major regulators of pre- and postsynaptic function compromised. Our findings highlight the complex molecular dysregulation in schizophrenia, with mitochondrial function downregulated versus signaling and trafficking upregulated, and synapse function disrupted; in combination with prior avenues of research, these finding support a role for energy deficits compromising highly ATP dependent neuronal function as a target for therapeutic interventions.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

SUBMITTER: Frank Koopmans

LAB HEAD: August B. Smit

PROVIDER: PXD058441 | Pride | 2026-03-09

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20220120_rklaas_SUN-schizo-cortex-layer1-3_4-6_DIA_G01-1_S2-A1_1_2271.d.zip	Other
	20220120_rklaas_SUN-schizo-cortex-layer1-3_4-6_DIA_G01-2_S2-A2_1_2272.d.zip	Other
	20220120_rklaas_SUN-schizo-cortex-layer1-3_4-6_DIA_G01-3_S2-A3_1_2273.d.zip	Other
	20220120_rklaas_SUN-schizo-cortex-layer1-3_4-6_DIA_G01-4_S2-A4_1_2274.d.zip	Other
	20220120_rklaas_SUN-schizo-cortex-layer1-3_4-6_DIA_G01-5_S2-A5_1_2275.d.zip	Other

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Publications

Human brain prefrontal cortex proteomics identifies compromised energy metabolism and neuronal function in Schizophrenia.

Koopmans Frank F Dijkstra Anke A AA Li Wei-Ping WP Klaassen Remco V RV Gouwenberg Yvonne Y Yao Shuyang S Bast Lisa L Verhage Matthijs M Karlsson Robert R Dwork Andrew J AJ Stockmeier Craig A CA Hjerling-Leffler Jens J Sullivan Patrick F PF Smit August B AB

Nature communications 20260129

Understanding the pathophysiological substrates of schizophrenia is a major challenge for current neuropsychiatric research. As part of a set of multi-omics experiments, we performed an extensive case-control proteomics study on 192 post-mortem tissue sections from prefrontal cortex from 96 individuals, including 47 cases with schizophrenia and 49 healthy controls. Using two independently measured cortical datasets, we identified 387 proteins differentially expressed between schizophrenia cases ...[more]

PMID: 41611717

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