Physical conditions such as insulin resistance and weight gain, which are known to commonly co-occur with psychiatric disorders like psychosis and depression, could be detectable years before the onset of the psychiatric disorder, researchers recently reported in JAMA Psychiatry. Below, researcher Benjamin Perry, MRCPsych, of the University of Cambridge, England, explains the reasons for the study, clinical implications of the findings, and directions of future research.
Q: What led you and your colleagues to study the link between childhood insulin levels and later mental health problems?
A: We chose to conduct this study for a few reasons. There is good evidence from meta-analyses and other observational studies that early signs of developing physical health problems, such as insulin resistance and weight gain, can be detected right at the onset of psychiatric disorders such as psychosis and depression in young adults. Left unchecked, this can lead to type 2 diabetes, obesity, cardiovascular diseases and ultimately an early death. Sadly, people with psychosis and depression live on average 10-15 years less than the general population, mostly because of physical comorbidity.
However, most of the existing research in the field has been cross-sectional, and/or has included people who already have a diagnosis of psychosis or depression. Therefore, it's been difficult to disentangle the direction of association (ie, the chicken and egg. What comes first - the physical or the mental health problems?). Also, previous research has mostly included single-point measures of cardiometabolic markers, yet repeat measures of these markers provide much greater resolution into potential underlying biological pathways. In our study, we aimed to address those limitations.
Q: Please briefly describe your study method and the most significant findings.
A: We were fortunate enough to be able to access data from the Avon Longitudinal Study of Parents and Children (ALSPAC), which is a United Kingdom (UK) population-representative cohort study of around 15,000 participants who have been followed since birth. ALSPAC is a really rich resource, so we were able to include a number of repeat measurements of body mass index (BMI) and insulin levels from early childhood through early adulthood. We used a statistical technique called growth mixture modeling to delineate distinct trends of BMI and insulin levels through childhood and adolescence. Then, we examined whether any specific cardiometabolic developmental trajectory was associated with psychosis and depression in adulthood, after taking into account a number of other possible explanations (confounders).
We found that a trend of persistently high insulin levels from as far back as age 9 years was associated with a higher risk of psychosis in adulthood. We also found that BMI increases around the age of puberty onset were strongly associated with a higher risk of depression in adulthood. These associations remained after taking a number of potential alternative explanations into account, including sex, ethnicity, social class, physical activity, smoking, alcohol and substance use, sleep problems, calorie intake, and childhood behavioral and emotional problems.
Taken together, the findings from our study suggest that the cardiometabolic comorbidity so often attached to adult depression and psychosis may have early-life beginnings, and may be detectable long before the onset of depression or psychosis, at least in some individuals.
Q: Were any of the outcomes surprising or different than expected?
A: Perhaps the main thing that stood out for us was that there appeared to be distinct associations between childhood/adolescent trends of BMI and insulin levels with depression and psychosis respectively. Disruptions to glucose-insulin homeostasis and obesity often go hand-in-hand since they predispose to each other; this may explain why people with depression and psychosis have similarly higher rates of both obesity and type 2 diabetes mellitus than the general population, particularly in chronic illness. Our results however suggest the biological mechanisms underlying this comorbidity may be different in people suffering from psychosis compared with depression.
Q: Do you feel there are any near-term applications of these findings in clinical practice?
A: Our findings underscore the crucial importance that all young people presenting with symptoms of depression and psychosis receive a full and comprehensive work-up of their physical health. Intervening early is the best way to improve long-term health outcomes, both physical and psychiatric, and is the best way to reduce the mortality gap sadly faced by people with depression and psychosis.
Q: Are you doing any more research on this topic, and are there any other studies you feel are needed?
A: We do have a number of other studies at various stages of completion which we are really excited about, and the present study really is only the beginning. For example, we don’t know how/why insulin levels might be raised from childhood and how this might increase the risk of psychosis in adulthood.
We also don’t know exactly why BMI increases around the age of puberty onset might predispose to depression in adulthood—particularly when the evidence for this was much stronger than for an association of persistently high BMI levels throughout childhood and depression in adulthood.
We are also motivated to conduct research that can benefit patients directly, for example with studies that might help clinicians more easily recognize the cardiometabolic risk of young people with depression and psychosis. Early intervention is the best way to improve longer term outcomes, both physical and psychiatric, and help to close the mortality gap sadly faced by people who have depression and psychosis.
Perry BI, Stochl J, Upthegrove R, et al. Longitudinal trends in childhood insulin levels and body mass index and associations with risks of psychosis and depression in young adults. JAMA Psychiatry. 2021 January 13;[Epub ahead of print].
Benjamin Perry, MRCPsych, is an academic clinical psychiatrist based at the University of Cambridge, England. He is funded by a fellowship from the UK National Institute for Health Research. Dr. Perry is passionate about improving our understanding of why people with mental disorders such as psychosis and depression suffer from a higher prevalence of physical health problems than the general population, and in finding the best ways to reduce this health inequality.
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