Peripheral biomarkers of treatment-resistant schizophrenia: Genetic, inflammation and stress perspectives

Abstract

Treatment-resistant schizophrenia (TRS) often results in severe disability and functional impairment. Currently, the diagnosis of TRS is largely exclusionary and emphasizes the improvement of symptoms that may not be detected early and treated according to TRS guideline. As the gold standard, clozapine is the most prescribed selection for TRS. Therefore, how to predict TRS in advance is critical for forming subsequent treatment strategy especially clozapine is used during the early stage of TRS. Although mounting studies have identified certain clinical factors and neuroimaging characteristics associated with treatment response in schizophrenia, the predictors for TRS remain to be explored. Biomarkers, particularly for peripheral biomarkers, show great potential in predicting TRS in view of their predictive validity, noninvasiveness, ease of testing and low cost that would enable their widespread use. Recent evidence supports that the pathogenesis of TRS may be involved in abnormal neurotransmitter systems, inflammation and stress. Due to the heterogeneity of TRS and the lack of consensus in diagnostic criteria, it is difficult to compare extensive results among different studies. Based on the reported neurobiological mechanisms that may be associated with TRS, this paper narratively reviews the updates of peripheral biomarkers of TRS, from genetic and other related perspectives. Although current evidence regarding biomarkers in TRS remains fragmentary, when taken together, it can help to better understand the neurobiological interface of clinical phenotypes and psychiatric symptoms, which will enable individualized prediction and therapy for TRS in the long run.

Schizophrenia Synaptic Pathology and Antipsychotic Treatment in the Framework of Oxidative and Mitochondrial Dysfunction: Translational Highlights for the Clinics and Treatment

“…Enforcing this strategy could be helpful to understand the weight of antipsychotic effects on oxidative stress markers as well as the impact of the redox balance on treatment response. This perspective is specifically relevant for disentangling, even with the limits of peripheral markers, the putative contribution or association of oxidative stress in the response or resistance to antipsychotic treatment [ 332 , 333 ].…”

Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review

“…PRS provides a weighted sum of the number of risk alleles in an individual, with higher scores indicating a higher genetic risk burden [ 184 ], and there is some evidence that a higher genetic risk burden indicates a higher likelihood of developing TRS [ 185 ]. The development of a PRS for TRS may eventually lead to a high predictive accuracy of TRS [ 186 ]. Future work may also want to focus on greater correlation between the genetic factors and clinical phenotype as well as studying the inter-relationships with other measures such as neuroimaging and cognitive and longitudinal outcome variables.…”

Relationship between clinical efficacy and plasma concentration-dose ratio of risperidone in patients with schizophrenia

“…Schizophrenia is a long-term and chronic process (Jiao et al ., 2022). Drug metabolism is a complicated process, including absorption, distribution, metabolism, and excretion.…”