Cortisol and cytokines in schizophrenia: A scoping review

With a complex etiology and chronic, disabling evolution, schizophrenia continues to represent a challenge for patients, clinicians, and researchers alike. Recent emphasis in research on finding practical blood-based biomarkers for diagnosis improvement, disease development prediction, and therapeutic response monitoring in schizophrenia, led to studies aiming at elucidating a connection between stress and inflammation markers.

We set here to explore recent literature aiming to understand the connection between cytokines and cortisol level changes in individuals with schizophrenia and their potential relevance as markers of clinical improvement under treatment. A search was completed in Pubmed, Embase, Web of Science, and APAPsycInfo databases with search terms: (cytokines) AND (cortisol) AND (schizophrenia). This provided 43 results from Pubmed, 82 results from Embase, 52 results from Web of Science, and 9 results from APA PsycInfo. After removing articles not fitting the criteria, 13 articles were selected.

While all studies included assess cortisol levels in individuals with schizophrenia, most of them included a healthy control group for comparisons there is diversity in the inflammation markers assessed - the most frequent being the IL-2, IL-4, IL-6, IL-8, and TNF-α. Eleven of the 13 studies compare stress and inflammatory markers in individuals with schizophrenia to healthy controls, one study compares two subgroups of patients with schizophrenia, and one study compares pre- and post-measures in the same group of individuals with schizophrenia.

The focus of the studies within the topic is diverse. Many of the selected studies found correlations between cortisol and inflammation markers, however, the direction of correlation and inflammatory markers included differed. A variety of mechanisms behind cortisol and immunological changes associated with schizophrenia were considered. Evidence was found in these studies to suggest that biological immune and stress markers may be associated with clinical improvement in participants with schizophrenia, however, the exact mechanisms remain to be determined.