Genes-Protein-Metabolite Networks in Schizophrenia: A Systems Biology Perspective

Abstract

Schizophrenia is a complex mental disorder characterized by disturbances in thinking, perception, emotions, and behaviour. This study aims to delve into the fundamental abnormalities found in the genetic, proteomic, and metabolic processes, specifically within the dorsolateral region of the prefrontal cortex (DLPFC). Our focus is on understanding how these abnormalities contribute to the manifestation of dysfunction in schizophrenia and providing potential insights into therapeutic targets. The DLPFC plays a crucial role in essential cognitive functions such as task switching, interference prevention, inhibition, planning, and working memory. By examining proteins, metabolites, and genetic components, our objective is to unravel the metabolic pathways and establish connections between these different elements. We aim to identify patterns that contribute to both functional (executive functioning) and behavioural (delusions and hallucinations) dysregulations unique to schizophrenia. Our investigations have revealed dysregulations in gene expression, chromatin remodelling, particularly in the DLPFC. This suggests disruptions in normal gene regulation mechanisms, abnormal protein expression and signalling pathways, shedding light on the molecular mechanisms involved and identifying potential biomarker proteins associated with schizophrenia. This emphasises the significance of interventions related to cytoskeleton, oligodendrocytes, and energy metabolism for diagnosis and targeted treatments. Through transcriptome analyses, we have discovered unique gene expression patterns in schizophrenia, revealing molecular subtypes, metabolic dysregulation, changes in metabolic gene expression, energy metabolism, and imbalances in neurotransmitters, which shed light on the influence of genetic variations on cognition and provide insights into the disorder’s molecular mechanisms. With our study, we also propose further investigation into the dysregulations involved in schizophrenia’s complex pathophysiology, which is necessary to uncover new markers or therapeutic targets, leading to advancements in research and treatment of the disorder.