Metabolic Proteins & Metabolites

• Approximately 60% of people with serious mental illness are overweight or obese and are 3 times more likely to have obesity than the general population [1].

• People with SMI have 2 -3 times the risk of Type 2 Diabetes [2,3,4].

• People with SMI have 2-3 times increased mortality from cardiovascular disease [5].

• Over 70% of deaths in those with SMI in the UK occur due to preventable physical illness [6].
  
  This is partly driven by lifestyle, diet, psychotropic medications and access to healthcare but increasing evidence from genomics [7], epigenomics [8], metabolomics [9], transcriptomics [10] and other areas of research indicate an important biological overlap between metabolic dysfunction and severe psychopathology.

• The association between metabolic dysfunction and SMI can no longer be attributed solely to side-effects of medication. 40.8% of drug-naïve patients are overweight or obese [11].

• A significant part of the core pathophysiology of SMI may be metabolic in nature and a focus on metabolic aspects of SMI is supported by preliminary evidence of efficacy for interventions such as the ketogenic diet and metformin in SMI. [12, 13].
  
  Through six workstreams, the hub will work to identify the underlying connections between metabolic dysfunction and SMI. And in doing so, accelerate scientific progress toward better physical and mental health for people living with SMI.
  
  

References

1. Afzal, M., Siddiqi, N., Ahmad, B., Afsheen, N., Aslam, F., Ali, A., Ayesha, R., Bryant, M., Holt, R., Khalid, H., Ishaq, K., Koly, K. N., Rajan, S., Saba, J., Tirbhowan, N., & Zavala, G. A. (2021). Prevalence of Overweight and Obesity in People With Severe Mental Illness: Systematic Review and Meta-Analysis. Frontiers in endocrinology, 12, 769309. https://doi.org/10.3389/fendo.2021.769309

2. Vancampfort, D., Wampers, M., Mitchell, A. J., Correll, C. U., De Herdt, A., Probst, M., & De Hert, M. (2013). A meta-analysis of cardio-metabolic abnormalities in drug naïve, first-episode and multi-episode patients with schizophrenia versus general population controls. World psychiatry : official journal of the World Psychiatric Association (WPA), 12(3), 240–250. https://doi.org/10.1002/wps.20069

3. Liu, Y. K., Ling, S., Lui, L. M. W., Ceban, F., Vinberg, M., Kessing, L. V., Ho, R. C., Rhee, T. G., Gill, H., Cao, B., Mansur, R. B., Lee, Y., Rosenblat, J., Teopiz, K. M., & McIntyre, R. S. (2022). Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: A systematic review and meta-analysis. Journal of affective disorders, 300, 449–461. https://doi.org/10.1016/j.jad.2021.12.110

4. Zhao Z, Okusaga OO, Quevedo J, Soares JC, Teixeira AL. The potential association between obesity and bipolar disorder: A meta-analysis. J Affect Disord. 2016 Sep 15;202:120-3. doi: 10.1016/j.jad.2016.05.059. Epub 2016 May 28. PMID: 27262632.

5. Nordentoft, M., Wahlbeck, K., Hällgren, J., Westman, J., Osby, U., Alinaghizadeh, H., Gissler, M., & Laursen, T. M. (2013). Excess mortality, causes of death and life expectancy in 270,770 patients with recent onset of mental disorders in Denmark, Finland and Sweden. PloS one, 8(1), e55176. https://doi.org/10.1371/journal.pone.0055176

6. Premature mortality in adults with severe mental illness (SMI). GOV.UK. (n.d.). Retrieved March 28, 2023, from https://www.gov.uk/government/publications/premature-mortality-in-adults-with-severe-mental-illness/premature-mortality-in-adults-with-severe-mental-illness-smi

7. Amare, A. T., Schubert, K. O., Klingler-Hoffmann, M., Cohen-Woods, S., & Baune, B. T. (2017). The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies. Translational psychiatry, 7(1), e1007. https://doi.org/10.1038/tp.2016.261

8. Gharipour, M., Barekatain, M., Sung, J., Emami, N., Sadeghian, L., Dianatkhah, M., Sarrafzadegan, N., & Jahanfar, S. (2020). The Epigenetic Overlap between Obesity and Mood Disorders: A Systematic Review. International journal of molecular sciences, 21(18), 6758. https://doi.org/10.3390/ijms21186758

9. Orešič, M. (2012). Obesity and psychotic disorders: Uncovering common mechanisms through metabolomics. Disease Models & Mechanisms, 5(5), 614–620. https://doi.org/10.1242/dmm.009845

10. Li, X., Su, X., Liu, J., Li, H., Li, M., 23andMe Research Team, Li, W., & Luo, X. J. (2021). Transcriptome-wide association study identifies new susceptibility genes and pathways for depression. Translational psychiatry, 11(1), 306. https://doi.org/10.1038/s41398-021-01411-w

11. Maina, G., Salvi, V., Vitalucci, A., D’Ambrosio, V., & Bogetto, F. (2008). Prevalence and correlates of overweight in drug-naïve patients with bipolar disorder. Journal of affective disorders, 110(1-2), 149–155. https://doi.org/10.1016/j.jad.2007.12.233

12. Danan, A., Westman, E. C., Saslow, L. R., & Ede, G. (2022). The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Frontiers in psychiatry, 13, 951376. https://doi.org/10.3389/fpsyt.2022.951376

13. Calkin, C. V., Chengappa, K. N. R., Cairns, K., Cookey, J., Gannon, J., Alda, M., O’Donovan, C., Reardon, C., Sanches, M., & Růzicková, M. (2022). Treating Insulin Resistance With Metformin as a Strategy to Improve Clinical Outcomes in Treatment-Resistant Bipolar Depression (the TRIO-BD Study): A Randomized, Quadruple-Masked, Placebo-Controlled Clinical Trial. The Journal of clinical psychiatry, 83(2), 21m14022. https://doi.org/10.4088/JCP.21m14022