Identification of Biomarkers in Neuropsychiatric Disorders Based on Systems Biology and Epigenetics

Abstract

Clinically useful biomarkers are available for some neuropsychiatric disorders like fragile X syndrome, Rett syndrome, and Huntington’s disease. Despite many decades of research on the pathogenesis of neuropsychiatric disorders like schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD), the exact pathogenesis of these disorders remains unclear, and there are no clinically useful biomarkers for these disorders. However, there is increasing evidence that abnormal epigenetic mechanisms of gene expression contribute to the pathogenesis of SZ, BD, and MDD. Both systems (or network) biology and epigenetics (a component of systems biology) attempt to make sense of biological systems that are highly dynamic and multi-compartmental. This article suggests that systems biology, emphasizing the epigenetic component of systems biology, could help identify clinically useful biomarkers in neuropsychiatric disorders like SZ, BD, and MDD.

Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers

“…While the search for clinically useful diagnostic biomarkers for neuropsychiatric disorders has a history spanning several decades, there is little in the way of successful outcomes to report for several reasons. Perhaps the most important of these is the existence of significant levels of heterogeneity which, in some cases, can be reduced to different subtypes for many of these disorders, which is reflected in the high levels of variation in gene expression or chromatin modification between tissues and patient populations [162]. While there has been great progress towards covering the common variant genetic heterogeneity through large mega GWAS and meta-analysis there have been no comprehensive meta-analyses on epigenetic diagnostic biomarker studies.…”

DNA Methylation and Schizophrenia: Current Literature and Future Perspective

“…A biological marker, or biomarker, is a trait that can be evaluated and measured as an indicator of biological process, pathological process, or treatment response [ 218 ]. There are currently no precise and functional biomarkers for neuropsychiatric disorders like schizophrenia [ 219 ]. Studies of epigenetic changes in schizophrenia hold promise for the development of diagnostic and prognostic biomarkers for schizophrenia and a therapeutic target [ 177 ].…”

Modeling SARS-CoV-2 infection in individuals with opioid use disorder with brain organoids

“… 62 – 64 OUD and other substance use disorders are usually compounded with additional neuropsychiatric disorders, such as depression, anxiety, schizophrenia, bipolar disorder, attention-deficit hyperactivity disorder (ADHD), psychotic illness, borderline personality disorder, and antisocial personality disorder. 65 – 68 Researchers have posed several reasons for such a high prevalence of comorbidity between OUD and other neuropsychiatric disorders: (1) they target similar brain regions (nucleus accumbens, ventral tegmental area, prefrontal cortex, hippocampus, amygdala) and neural circuitry (implicating the reward system, decision making, impulse control, stress response, and emotions) 66 – 68 ; (2) they share common molecular mechanisms affected by various genetic, epigenetic, and environmental factors such as genetic mutations, stress, adversity, trauma, and drug exposure and/or access 62 , 65 – 67 , 69 – 71 ; (3) there are numerous clinical similarities and overlapping symptoms with each other, and one disease may unmask or exacerbate the symptoms of the other. 67 However, the precise mechanisms for many neuropsychiatric diseases, including OUD, are unclear, and further investigation is crucial for a greater understanding of the nature of these diseases and their complex relationship.…”