The challenges at the core of multimorbidity research

Multimorbidity is common in those with mental illness, and further deterioration of mental health, reduced quality of life, and premature mortality have been reported in those with multiple disorders. 1 Momen NC Plana-Ripoll O Agerbo E et al. Mortality associated with mental disorders and comorbid general medical conditions. JAMA Psychiatry. 2022; 79: 444-453 Crossref PubMed Scopus (31) Google Scholar , 2 Barnes AL Murphy ME Fowler CA Rempfer MV Health-related quality of life and overall life satisfaction in people with serious mental illness. Schizophr Res Treatment. 2012; 2012: 245103 Crossref PubMed Google Scholar , 3 Launders N Dotsikas K Marston L Price G Osborn DPJ Hayes JF The impact of comorbid severe mental illness and common chronic physical health conditions on hospitalisation: a systematic review and meta-analysis. PLoS One. 2022; 17: e0272498 Crossref PubMed Scopus (9) Google Scholar Given that comorbidity is often an exclusion criterion in intervention studies, 4 Stoll CRT Izadi S Fowler S et al. Multimorbidity in randomized controlled trials of behavioral interventions: a systematic review. Health Psychol. 2019; 38: 831-839 Crossref PubMed Scopus (20) Google Scholar evidence from observational studies plays a crucial role in our understanding of its associations with health outcomes. The systematic review and meta-analysis presented by Sean Halstead and colleagues 5 Halstead S Cao C Høgnason Mohr G et al. Prevalence of multimorbidity in people with and without severe mental illness: a systematic review and meta-analysis. Lancet Psych. 2024; (published April 17.)https://doi.org/10.1016/S2215-0366(24)00091-9 Google Scholar provides estimates of multimorbidity (ie, the coexistence of two or more chronic physical conditions [physical multimorbidity] and the coexistence of three or more psychiatric disorders [psychiatric multimorbidity]) in those with schizophrenia-spectrum disorder and bipolar disorder. They report that 25% (95% CI 0·19–0·32) of individuals with these severe mental illnesses have physical multimorbidity, which represents 2·40 (95% CI 1·57–3·65, p=0·0009) times the prevalence in people without severe mental illness, highlighting the pervasiveness of multimorbidity in this population. Furthermore, the authors report that 14% (95% CI 0·08–0·23) of those living with schizophrenia-spectrum disorder and bipolar disorder experience psychiatric multimorbidity. Included studies were predominantly cross-sectional studies carried out in North America or Europe, with high heterogeneity (I2>90%). Based on this comprehensive review, we would like to point out several challenges that remain in the larger context of multimorbidity research. The concept of multimorbidity is extremely complex and arguably impractical to be fully captured in epidemiological research studies—a wide range of disorders; variation in the number, severity, and treatment of comorbidities; different dates of onset (and potentially recovery); and multiple pathways. Thus, multimorbidity research requires simplification. Yet, it remains challenging to achieve simplicity without compromising on the comprehensiveness. The challenge is evident in the 82 studies included in the systematic review by Halstead and colleagues; 5 Halstead S Cao C Høgnason Mohr G et al. Prevalence of multimorbidity in people with and without severe mental illness: a systematic review and meta-analysis. Lancet Psych. 2024; (published April 17.)https://doi.org/10.1016/S2215-0366(24)00091-9 Google Scholar only four studies considered both physical and psychiatric multimorbidity. Limited definitions of multimorbidity are also seen more widely in the literature, as described by Skou and colleagues. 6 Skou ST Mair FS Fortin M et al. Multimorbidity. Nat Rev Dis Primers. 2022; 8: 48 Crossref PubMed Scopus (180) Google Scholar Researchers often consider disorder pairs, counts of conditions within a list, or weighted indices. The pitfalls of using counts and weighted indices have previously been highlighted, 7 Nicholson K Almirall J Fortin M The measurement of multimorbidity. Health Psychol. 2019; 38: 783-790 Crossref PubMed Scopus (41) Google Scholar including that researchers need to consider the populations and outcomes for which they were developed. Halstead and colleagues 5 Halstead S Cao C Høgnason Mohr G et al. Prevalence of multimorbidity in people with and without severe mental illness: a systematic review and meta-analysis. Lancet Psych. 2024; (published April 17.)https://doi.org/10.1016/S2215-0366(24)00091-9 Google Scholar found that, compared with those without severe mental illness, the prevalence of multimorbidity was 4 times higher (odds ratio [OR] 3·99, 95% CI 1·43–11·10) among individuals with severe mental illness younger than 40 years, but 1·5 times higher (OR 1·55, 95% CI 0·96–21) for those older than 40 years, indicating that relevant comorbid diseases are likely to differ by age. Well designed, thorough lists and indices can facilitate multimorbidity research through consideration of a variety of disorders, but the potential for interaction between psychiatric and physical disorders on associations should also be considered. 8 Pan T Anindya K Devlin N et al. The impact of depression and physical multimorbidity on health-related quality of life in China: a national longitudinal quantile regression study. Sci Rep. 2022; 12: 21620 Crossref PubMed Scopus (3) Google Scholar , 9 Ho C Feng L Fam J Mahendran R Kua EH Ng TP Coexisting medical comorbidity and depression: multiplicative effects on health outcomes in older adults. Int Psychogeriatr. 2014; 26: 1221-1229 Crossref PubMed Google Scholar Depending on the nature of data, it might be possible for researchers to consider more complex patterns of comorbidity, as shown by Weye and colleagues. 10 Weye N Momen NC Whiteford HA et al. The contribution of general medical conditions to the non-fatal burden of mental disorders: register-based cohort study in Denmark. BJPsych Open. 2022; 8: e180 Crossref PubMed Scopus (2) Google Scholar Prevalence of multimorbidity in people with and without severe mental illness: a systematic review and meta-analysisThis is the first meta-analysis to estimate physical alongside psychiatric multimorbidity prevalence, showing that these are common in people with schizophrenia-spectrum disorder and bipolar disorder. The greater burden of physical multimorbidity in people with severe mental illness compared with those without is higher for younger cohorts, reflecting a need for earlier intervention. Our findings speak to the utility of multimorbidity for characterising the disease burden associated with severe mental illness, and the importance of facilitating integrated physical and mental health care. Full-Text PDF