UHPLC-HRMS Links Blood Chemistry to BMI in Schizophrenia

Obesity is very common in people with schizophrenia (SCZ) and tends to make both their mental symptoms and thinking abilities worse. However, exactly why this happens on a biological level is not well understood. Researchers at Tianjin Anding Hospital in China set out to investigate this by looking for patterns in blood chemistry that relate to body weight in people with long-term schizophrenia. They collected blood samples after participants had fasted, then used ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) to get a detailed picture of the various substances present. Their findings were published in the journal Schizophrenia Research.¹

Why Does Obesity in Schizophrenia Matter, and What Don't We Understand About It Yet?

Schizophrenia is a serious, long-term mental illness that places a heavy burden on both the people who have it and society at large.^2,3Research shows that nearly half of people with schizophrenia are affected by obesity,a rate which is two to three times higher than what is seen in the general population.^4,5A higher body mass index (BMI), a common way to measure obesity, is a notable and clinically important trait in people with schizophrenia. It is worth pointing out that having a high BMI in this group is not just a separate metabolic issue tacked on alongside schizophrenia, but rather it is closely tied to a greater risk of heart and metabolism-related problems, worse thinking and memory performance, and poorer outcomes over the long run.^6,7nThese findings suggest that obesity in people with schizophrenia might stem from underlying biological changes that go beyond just lifestyle habits or medication side effects. Still, scientists do not have a clear understanding of what is happening on a metabolic level that sets apart patients with higher versus lower BMI.⁸

How Does Blood Chemistry Differ Between Higher- and Lower-BMI Schizophrenia Patients, and Is This Linked to Symptoms or Cognition?

The study included 347 people with long-term schizophrenia, who were split into two groups based on whether they had a higher or lower body mass index (BMI). To assess their mental health symptoms and thinking abilities, the researchers used two standard evaluation tools; The Positive and Negative Symptom Scale (PANSS), which measures psychiatric symptoms, and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), which tests memory, attention, and other cognitive skills. The researchers then used several statistical techniques to compare the two groups, identify meaningful patterns, and test how well certain substances could predict a person's weight category.¹

The team found 58 substances in the blood that differed meaningfully between the higher and lower BMI groups, mostly involving amino acids (building blocks of protein) and fatty acids. Further analysis showed notable disruptions in three biological processes: one involved in producing the amino acid arginine, one related to niacin (vitamin B3) processing, and one involved in breaking down the amino acid phenylalanine.¹

When the researchers combined certain amino acids and fatty acids together, they were able to reasonably predict whether someone was likely to have a higher BMI. Additionally, two specific substances (C-mannosyl valine and C-mannosyl phenylalanine) were linked to worse cognitive performance in the lower BMI group, while another substance (2-aminoheptanoic acid) was linked to more severe negative symptoms (such as reduced motivation or emotional expression) in the higher BMI group.¹

“Distinct metabolic profiles, wrote the authors of the paper,¹ “characterize BMI heterogeneity in SCZ and are differentially associated with cognitive impairment and negative symptoms.”

Read More on Similar Subjects
HPLC Analysis of Plasma H₂S Reveals Insights into Cognitive Improvement in Schizophrenia
Chromatography Uncovers Potential Obesity Biomarkers

References

1. Chi, J.; Han, Y.; Zhang, X. et al. Metabolomics Analysis Reveals BMI-Related Metabolic Characteristics in Schizophrenia Patients. Schizophr Res. 2026, 296, 218-226. DOI: 10.1016/j.schres.2026.07.012
2. Huang, Y.; Wu, K.; Li, H. et al.Homocysteine Level, Body Mass Index and Clinical Correlates in Chinese Han Patients with Schizophrenia. Sci. Rep.2020, 10 (1), 16119. DOI: 10.1038/s41598-020-72934-3
3. Tiffin, P. A.; Welsh, P. Practitioner Review: Schizophrenia Spectrum Disorders and the At-Risk Mental State for Psychosis in Children and Adolescents--Evidence-Based Management Approaches. J. Child Psychol. Psychiatry2013, 54 (11), 1155-1175. DOI: 10.1111/jcpp.12136
4. Li, Q.; Du, X.; Zhang, Y. et al. The Prevalence, Risk Factors and Clinical Correlates of Obesity in Chinese Patients with Schizophrenia. Psychiatry Res.2017, 251, 131-136. DOI: 10.1016/j.psychres.2016.12.041
5. Manu, P.; Dima, L.; Shulman, M. et al. Weight Gain and Obesity in Schizophrenia: Epidemiology, Pathobiology, and Management. Acta Psychiatr. Scand.2015, 132 (2), 97-108. DOI: 10.1111/acps.12445
6. Liu, C.; Zhang, Z.; Wang, B. et al. Global Health Impacts of High BMI: A 30-Year Analysis of Trends and Disparities Across Regions and Demographics. Diabetes Res. Clin. Pract.2024, 217, 111883. DOI: 10.1016/j.diabres.2024.111883
7. Zeng, M. Wang, X.; Zhou, J. et al. Body Mass Index-Specific Metabolic Profiles in Schizophrenia: Implications for Cognitive Dysfunction and Psychopathology. J. Neural Trans2025, 132, 1197–1208. DOI:10.1007/s00702-025-02951-x
8. Corbin, L. J.; Timpson, N. J. Body Mass Index: Has Epidemiology Started to Break Down Causal Contributions to Health and Disease? Obesity 2016, 24 (8), 1630-1638. DOI: 10.1002/oby.21554