Advances in Postmortem Brain Analysis: Correcting for Decay to Better Understand Schizophrenia

Recent research conducted by Skoltech scientists has shed light on the stability of small molecules in postmortem brain tissues, paving the way for more accurate studies of neurological disorders such as schizophrenia. The team examined brain samples from humans, mice, and rats, focusing on nearly 1,000 small molecules, including lipids and metabolites, during the critical initial hours and days following death.

Their findings reveal that approximately 77% of the studied lipids and 25% of the metabolites remain relatively stable within the first 48 hours postmortem, despite the natural tissue decay. This stability allows researchers to distinguish disease-related molecular changes from those caused by tissue degradation, ultimately improving the reliability of postmortem analyses.

The study documented degradation trends across three species—humans, mice, and rats—monitoring the levels of small molecules at death and at multiple intervals over 48 hours. Notably, the decay of most lipids and metabolites can be compensated for in future research, enabling scientists to establish a baseline for healthy brains and compare it with pathological conditions.

This work is particularly significant for the study of psychiatric disorders like schizophrenia and depression, where understanding molecular signatures is crucial. Currently, the underlying biology remains poorly understood due to limitations posed by tissue decay. By providing a method to correct for these effects, the researchers open new avenues for exploring disease-specific molecular footprints in brain tissue.

While focused on healthy brains, the study offers a foundational reference point that will facilitate the calibration of data from diseased tissues. The advanced mass spectrometry techniques employed provided high-resolution measurements of small molecule distributions over time, offering insights into the natural decay process.

According to lead researcher Marina Zavolskova, this research addresses a critical gap in postmortem brain studies: "We now have the tools to account for tissue decay, making it easier to differentiate between true disease markers and postmortem artifacts." These findings are published in the journal Biomolecules and mark a significant step forward in molecular neuroscience research, with broad implications for diagnosing and understanding mental health disorders.

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