The University of Glasgow’s Institute of Health and Wellbeing is considered world-leading in health and biomedical informatics research, advancing the use of routine health data and record linkage for research. We are well-placed in Glasgow to develop eCohorts for mental health that can be accessed by researchers from across the UK and internationally. For this project, we will extend several ongoing large scale, national-level data linkage studies with the aim of understanding predictors and modifiers of, and potential novel treatments for, mental health problems.
1) Antihypertensives as repurposed treatments for mood and cognitive disorders
Recent genetic research suggests that mood disorders and hypertension may share common biological pathways1. Preliminary evidence suggests that certain types of antihypertension medications (ACE inhibitors and angiotensin-receptor blockers (ARBs)) may be useful as repurposed treatments for depression and bipolar disorder2
Using linked health data, we recently found that treatment with ACE-inhibitors or ARBs (compared to other classes of antihypertensive) was associated with lower rates of new-onset hospital admission for mood disorders3, suggesting a possible role for ARBs in the treatment of mood disorders.
We have been working with the Information Services Division (ISD) of NHS Scotland to identify, an eCohort of individuals treated with antihypertensive medications (and controls) which will allow us to assess whether different classes of antihypertensive are effective in preventing future mood disorder outcomes. We plan to extend this work to also assess associations between different classes of antihypertensives with cognitive disorders and dementia.
2) Patterns of prescribing and clinical outcomes in bipolar disorder
In patients with bipolar disorder, lithium is recommended as the first-line treatment, but its use is in decline. We have successfully linked Scottish national prescription data for lithium to NHS data on hospital admissions and outpatient appointments to evaluate prescribing patterns for BD over the last eight years. We plan to extend this work to assess the impact of lithium therapy (compared to treatment with other medications such as atypical antipsychotics) on the long-term physical health and mortality outcomes of patients with bipolar disorder. Specifically, we are interested in assessing whether bipolar disorder patients treated with lithium are less likely than those treated with antipsychotics to develop cardiometabolic disease (ischaemic heart disease, stroke and diabetes) and dementia.
3) Using the SHARE population register to investigate the pharmacogenomics of lithium response in bipolar disorder
‘SHARE’ (https://www.registerforshare.org/) is a unique register of people in Scotland who have consented to being approached to take part in research studies that make use of their routine clinical data, including consent for the use of genomic data taken from blood samples. So far, there are 190,000 individuals on the SHARE register, including around 1,000 individuals with a diagnosis of bipolar disorder plus a record of being treated with lithium. Of these, 500 have provided a sample of DNA. We will invite all of these individuals to a detailed assessment of associations between genetic factors and responsiveness to lithium treatment
- Craddock N, Sklar P. Bipolar Disorder 1 - Genetics of bipolar disorder. Lancet 2013. doi:10.1016/S0140-6736(13)60855-7.
- Ostacher MJ, Iosifescu D V., Hay A, Blumenthal SR, Sklar P, Perlis RH. Pilot investigation of isradipine in the treatment of bipolar depression motivated by genome-wide association. Bipolar Disord 2014. doi:10.1111/bdi.12143.
- Boal AH, Smith DJ, McCallum L, Muir S, Touyz RM, Dominiczak AF, et al. Monotherapy with major antihypertensive drug classes and risk of hospital admissions for mood disorders. Hypertension 2016. doi:10.1161/HYPERTENSIONAHA.116.08188.