Research Paper Advance Articles
mTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease
- 1 Woodinville Psychiatric Associates, Woodinville, WA 98072, USA
- 2 Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA
- 3 Life Sciences, Virginia Commonwealth University, Richmond, VA 23284, USA
- 4 Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, UK
- 5 Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
- 6 MRC Health Data Research UK (HDR UK), London, UK
Received: December 19, 2023 Accepted: July 5, 2024 Published: July 26, 2024
https://doi.org/10.18632/aging.206033How to Cite
Copyright: © 2024 Berner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Gain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response.
Methods: Twenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response.
Results: mTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance.
Conclusions: The data illustrate the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response.
Abbreviations
AUC: Area under the curve; AQ-10: 10-item Autism Spectrum Quotient; BMI: Body mass index; BSA: Bovine serum albumin; CI: Confidence interval; EDTA: Ethylenediaminetetraacetic acid; FDA: Food and drug administration; GAD-7: 7-item Generalized Anxiety Disorder; IL: Interleukin; KSP-6: 6-item Karolinska Scales of Personality; LiTMUS: Lithium Treatment-Moderate dose Use Study; mTORC1: mammalian target of rapamycin complex 1; NMDA: N-methyl-D-aspartate; PC: Principal component; PCA: Principal component analysis; PHQ-9: 9-item Patient Health Questionnaire; RIPA: Radioimmunoprecipitation assay; SD: Standard deviation; SDS: Sodium dodecyl sulfate; p70S6K: 70 ribosomal S6 kinase; UMAP: Uniform manifold approximation and projection; 4EBP1: 4E-binding protein 1.