Hub for Metabolic Psychiatry

Metabolic psychiatry is a critical but under-researched area. Individuals with severe mental illness (SMI) are at increased risk of obesity, diabetes, cardiovascular disease and premature mortality. There are established bidirectional mechanisms between SMI and metabolic disorders and recent research suggests that metabolic interventions may be therapeutic for SMI.

The Hub for Metabolic Psychiatry will have three overarching objectives: a) to drive discovery science in metabolic psychiatry; b) to develop and test novel metabolism-based treatment approaches for SMI in collaboration with people with lived experience of SMI; and c) to build UK-wide capacity for future metabolic psychiatry research and clinical innovation.

We will have four experimental workstreams:

1. Genomics and causal inference: Data from genomics research has identified that adiposity traits are causally related to major depressive disorder. There are also positive genetic correlations between diabetes and SMI but the causal direction of these associations is unclear. Further, there may be important differences in these associations according to ethnicity/ancestry. This workstream will use causal inference methods such as Mendelian randomisation to better understand the shared biology of SMI and metabolic disorders.

2. Health informatics and data science: We will use data linkage within multiple national and international datasets to investigate obesity/diabetes and SMI, with a focus on identifying patterns of comorbidity and predictors of both psychiatric and metabolic outcomes. These datasets include SCI-Diabetes data in Scotland, virtual patient cohorts from the NHS Information Services Division, Edinburgh DataLoch, UK-wide Clinical Practice Research Datalink, and multiple national-level datasets from Denmark.

3. Metabolic biomarkers of clinical outcomes in SMI: We will identify metabolomic biomarkers of SMI and conduct a 12-month prospective study to assess how changes in metabolic profile relate to clinical and functional outcomes. This workstream will deploy several innovative data collection methods, including continuous monitoring of metabolic biomarkers, radar-based and actigraph assessments of sleep and circadian rhythms, ecological momentary assessments of mental state and state-of-the-art metabolomics analyses.

4. Co-developing and testing novel metabolism-based interventions for SMI: Working closely with the James Lind alliance and The McPin Foundation, we will co-develop and assess the acceptability and therapeutic potential of a range of metabolic interventions as novel treatments for SMI, including digital approaches, chrononutrition (time restricted eating), the ketogenic diet, low carb diets, metformin and GLP1 receptor antagonists. This work will prioritise and co-design future clinical trials of metabolic interventions for SMI.

Two additional cross-cutting workstreams will feed into the four experimental workstreams:

5. Data analysis and open science workstream: We will develop and test statistical approaches - including dynamic structural equation modelling and machine learning - for each of the workstreams above and create a data curation and data sharing platform to maximise the open science opportunities of this work.

6. Patient and public involvement, engagement and dissemination workstream: The McPin Foundation will help with each of the workstreams to ensure that people with lived experience of SMI are at the heart of this work, from experimental design to dissemination and knowledge exchange activities.

Overall, the Hub for Metabolic Psychiatry represents an innovative programme of lived experience involvement, discovery science and clinical research within an area that is extremely high priority for people with SMI and their families. It fills an important gap in the current research landscape and will place the UK at the forefront of future metabolic psychiatry research and innovation.

Metabolic psychiatry is a critical but under-researched area. Individuals with severe mental illness (SMI) are at increased risk of obesity, diabetes, cardiovascular disease and premature mortality. There are established bidirectional mechanisms between SMI and metabolic disorders and recent research suggests that some metabolic interventions may be therapeutic for SMI. The Hub for Metabolic Psychiatry will have four experimental workstreams: 1. Genomics and causal inference within large-scale genetic datasets to better understand the shared biology of SMI and metabolic disorders; 2. Health informatics and data science approaches within multiple routine linked healthcare datasets to investigate the interface between obesity/diabetes and SMI (with a focus on identifying patterns of comorbidity and predictors of health outcomes); 3. Identifying metabolic biomarkers of clinical outcomes in SMI within a 12-month prospective study that will also assess how changes in metabolic profile and sleep and circadian factors relate to clinical and functional outcomes; and 4. Co-developing and testing novel metabolism-based interventions for SMI such as digital approaches, time-restricted eating, the ketogenic diet, low carb diets, metformin and GLP1 receptor agonists. Two additional cross-cutting workstreams will feed into each stage of the four experimental workstreams: 5. Data analysis and open science; and 6. Patient and public involvement, engagement and dissemination activities (in collaboration with by The James Lind Alliance and The McPin Foundation). Overall, The Hub for Metabolic Psychiatry represents an innovative programme of discovery science, clinical research and lived experience collaboration at the interface between mental illness and metabolism.