Abstract
Schizophrenia (SCZ) is a neurodevelopmental disorder with a high genetic component, but the presence of environmental stressors can be important for its onset and progression. Cannabis use can be a major risk factor for developing SCZ. However, despite the available data on the neurobiological underpinnings of SCZ, there is an important lack of studies in human neuronal tissue and living cells addressing the effects of cannabis in SCZ patients. In this study, we analysed the most relevant bio-macromolecular constituents in olfactory neuroepithelium (ON) cells of healthy controls non-cannabis users, healthy cannabis users, SCZ patients non-cannabis users, and SCZ patients cannabis users using Synchrotron Radiation-Fourier Transform Infrared (SR-FTIR) spectrometry and microscopy. Our results revealed that SCZ patients non-cannabis users, and healthy cannabis users exhibit similar alterations in the macromolecular profile of ON cells, including disruption in lipid composition, increased lipid membrane renewal rate and lipid peroxidation, altered proteins containing more β-sheet structures, and showed an increase in DNA and histone methylation. Notably, these alterations were not observed in SCZ patients who use cannabis regularly. These data suggest a differential effect of cannabis in healthy controls and in SCZ patients in terms of the macromolecular constituents of ON cells.
Highlights
Schizophrenia (SCZ) is a highly prevalent chronic and severe neuropsychiatric disorder
Differences in Global Assessment of Functioning (GAF) scores were observed between groups (K = 14.60; p < 0.01), with SCZ patients non-cannabis users (SCZ/nc) (p < 0.05) and SCZ patients cannabis users (SCZ/c) (p < 0.05) showing significantly lower GAF scores than healthy controls non-cannabis users (HC/nc)
In terms of cannabis use, no significant differences were observed between groups for age of first use or units per week, while a significantly longer length of use was observed in SCZ/c with respect to healthy controls cannabis users (HC/c) (U = 1.00; p < 0.05)
Summary
Schizophrenia (SCZ) is a highly prevalent chronic and severe neuropsychiatric disorder. The double hit hypothesis states that genetic factors together with the presence of one or several environmental cues are necessary for the disease to initiate its chronic course [11] In this sense, the highly prevalent consumption of drugs of abuse in the SCZ population, cannabis, could impact the onset, development, and chronicity of the disease [12]. Obtaining viable neurological tissue to study how biomarkers of disease are modulated by drugs such as cannabis in living patients has proven challenging In this sense, the olfactory neuroepithelium (ON) has great potential as a surrogate model of central nervous system function to study the molecular processes involved in some neuropsychiatric disorders such as SCZ [19]. We compared the IR spectral profile of ON cells derived from SCZ patients non-cannabis users (SCZ/nc), and SCZ patients cannabis users (SCZ/c) with those of healthy controls non-cannabis users (HC/nc), and healthy controls cannabis users (HC/c)
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