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AimSchizophrenia involves complex interactions between biological and environmental factors, including childhood trauma, cognitive impairments, and premorbid adjustment. Predicting its severity and progression remains challenging. Biomarkers like glial cell line-derived neurotrophic factor (GDNF) and miRNA-29a may bridge biological and environmental aspects. The goal was to explore the connections between miRNAs and neural proteins and cognitive functioning, childhood trauma, and premorbid adjustment in the first episode of psychosis (FEP).MethodThis study included 19 FEP patients who underwent clinical evaluation with: the Childhood Trauma Questionnaire (CTQ), the Premorbid Adjustment Scale (PAS), the Positive and Negative Syndrome Scale (PANSS), and the Montreal Cognitive Assessment Scale (MoCA). Multiplex assays for plasma proteins were conducted with Luminex xMAP technology. Additionally, miRNA levels were quantitatively determined through RNA extraction, cDNA synthesis, and RT-qPCR on a 7500 Fast Real-Time PCR System.ResultsAmong miRNAs, only miR-29a-3p exhibited a significant correlation with PAS-C scores (r = -0.513, p = 0.025) and cognitive improvement (r = -0.505, p = 0.033). Among the analyzed proteins, only GDNF showed correlations with MoCA scores at the baseline and after 3 months (r = 0.533, p = 0.0189 and r = 0.598, p = 0.007), cognitive improvement (r = 0.511, p = 0.025), and CTQ subtests. MIF concentrations correlated with the PAS-C subscale (r = -0.5670, p = 0.011).ConclusionGDNF and miR-29a-3p are promising as biomarkers for understanding and addressing cognitive deficits in psychosis. This study links miRNA and MIF to premorbid adjustment and reveals GDNF’s unique role in connection with childhood trauma.

IntroductionThe standard care of schizophrenia patients is based on the assessment of their psychotic behavior, using interview-based, subjective scales that measure symptoms severity. We aimed at defining easily accessible and inexpensive blood-derived clinical diagnostic parameters that might serve as objective markers in the prediction of the effects of pharmacological treatment of schizophrenia patients.MethodsA total of 40 patients with schizophrenia diagnosis according to ICD 10 during psychotic decompensation were included in the study. Blood-based biochemical parameters, BMI and interview-based medical scales of symptom severity were determined – all at admission and after 12 weeks of standard pharmacological treatment.ResultsThe drops in scale values were correlated with clinical parameters. All scale changes after treatment were dependent on the value of the given scale at admission, with higher initial values leading to larger drops of the values after treatment. Models based on those correlations were significantly improved when immune and metabolism parameters were included. C4 complement and C-reactive protein (CRP) level at admission were predictive of changes in Positive and Negative Syndrome Scale (PANSS) subscales related to significant disruption of thought processes, reality testing and disorganization. The pharmacological treatment-driven changes in scales representing negative symptoms were correlated with markers of the patients’ thyroid status and metabolism.DiscussionWe show that objective markers can be obtained by testing immune and metabolic parameters from the patients’ blood and may be added at a low cost to the standard care of schizophrenia patients in order to predict the outcome of pharmacological treatment.