Neurotransmitter Biomarkers

Schizophrenia spectrum disorders (SSD) are characterized as a multidimensional and severe mental illness, involving abnormalities at various levels, including molecular processes, brain structure, and function. The complex pathophysiology of SSD arises from the interactive influence of multiple factors rather than a singular predominant element. This chapter presents a comprehensive review spanning a 12-year period (2011–2023) dedicated to scrutinizing studies focused on developing diagnostic models for SSD utilizing neurotransmitter biomarkers, emphasizing on assessment through receiver operating characteristic (ROC) analysis. The screening process included 12 articles, spanning 8 countries, and involving around 1,000 SSD patients. While several studies explored molecules associated with glutamatergic pathways, such as glutamate and GABA, their individual performance was found to be moderate. Notably, a model incorporating three components of the endocannabinoid system demonstrated an area under the curve (AUC) of 94%. A standalone agmatine model yielded an AUC of 97%. A model utilizing a cognitive domain as a predictor exhibited an AUC of 92%, surpassing the performance of a catecholamine panel (AUC 86%) in distinguishing SSD patients from healthy controls. These findings underscore the complexity of SSD and the importance of considering diverse factors, including choice of biomarkers and their contextual measurement, for constructing more efficient diagnostic models.