Is Schizophrenia and Psychosis Related to Accelerated Aging?

Is increased mortality and morbidity in patients with schizophrenia related to accelerated aging due to the disorder? Researchers investigated this question in a new paper, finding evidence of faster aging measures in patients with schizophrenia vs controls.¹ The results support a concept of accelerated aging in schizophrenia, outside of common explanations for aging like familial risk, smoking, and others. We spoke with researcher on the study, Ethan Whitman, to learn more about these findings.

Psychiatric Times: What inspired your research into aging in relation to schizophrenia?

Ethan Whitman: This work was initially inspired by observations in the clinic. During my PhD, I rotated on a neuropsychology consult team at a psychiatric hospital. I was struck by how many of our referrals for cognitive decline were for patients with psychosis. Likewise, I noticed that these patients tended to be younger than what is typical for mild cognitive impairment or dementia. I started reading and learned there is a great psychiatric epidemiology literature showing that psychosis often precedes early onset of not just dementia, but a wide variety of age-related illnesses.^2,3 This has led some to hypothesize that people with schizophrenia undergo accelerated aging, thereby increasing risk of many different disorders simultaneously. If this hypothesis is true, that might support closer integration of preventive medicine with traditional psychiatric care for patients with psychosis.

PT: How did your unique biomarker imaging allow for testing of whole-body aging?

Whitman: We used data from the Dunedin Study—a longitudinal study of 1037 people born in Dunedin, New Zealand from 1972 to 1973 who have been followed since birth. We generated the biomarker in 2 steps.

In the first step, we repeatedly measured a comprehensive panel of biomarkers in this cohort over a 20-year period. These biomarkers included things like blood pressure, body mass index, cholesterol, lung function, dental caries, and several others. Then we looked at the changes in these biomarkers from age 26 to 45 years and used these changes to calculate a whole-body score for how fast each study member was aging.

In the second step, we used brain structural MRI data collected in the Dunedin Study at age 45 to build a machine-learning algorithm that accurately estimates the whole-body aging score that we made in step 1. We call this estimate Dunedin Pace of Aging Calculated from NeuroImaging, or DunedinPACNI. This algorithm can be used to generate scores for any new brain MRI scan. We have previously found that DunedinPACNI scores can predict future cognitive decline, incident disease, and all-cause mortality in multiple different datasets.

For this study, we applied our algorithm to brain MRI scans from datasets of adults with schizophrenia, unaffected first-degree siblings of schizophrenia patients, youth at clinical high-risk for psychosis, and healthy controls. This algorithm gave us our measure of whole-body aging in each of these groups.

PT: What should clinicians take away from your results?

Whitman: We saw the same pattern of accelerated aging in schizophrenia in 3 different datasets, so this finding appears very replicable.

I would also highlight that we do not see any differences in aging between unaffected first-degree siblings of schizophrenia patients and healthy controls. So, the robust pattern of accelerated aging in schizophrenia does not seem to be a result of familial risk factors such as genetic propensity or early life environment, since these factors would also affect the siblings.

PT: What other reasons for aging were you able to rule out as causes of accelerated aging in your participants with schizophrenia?

Whitman: First, we ruled out tobacco smoking. People with schizophrenia tend to smoke cigarettes much more often than the general population. Smoking is also known to accelerate aging. So, we wanted to make sure that our findings were not just due to differences in tobacco use. Our analyses suggest that smoking might account for some of the association between schizophrenia and accelerated aging, but there is still a clear pattern of accelerated aging that is not attributable to tobacco smoking.

We also ruled out effects of antipsychotic medication use. Long term antipsychotic use comes with iatrogenic side effects, especially on metabolic health. We wanted to see if our findings were simply due to these side effects, so we also analyzed measures of lifetime antipsychotic exposure. We did not find any evidence to suggest that antipsychotic medication use accounted for the patterns of accelerated aging in schizophrenia.

Our group has also previously found that smoking and antipsychotic medication do not explain patterns of accelerated aging in schizophrenia when aging is measured with epigenetic biomarkers.⁴ So, our new results are in line with these prior findings, too.

PT: Was clinical high-risk for psychosis associated with the aging biomarker?

Whitman: We did not find any evidence for accelerated aging in youth at clinical high-risk for psychosis. Relatedly, we found that the pattern of accelerated aging was much stronger when we compared the oldest schizophrenia patients to the oldest healthy controls. Put differently, people who are in the early stages of psychosis (or simply at clinical high-risk) have much little to no accelerated aging while people who have experienced psychosis for many years show far more dramatically accelerated aging.

We do not know for sure yet, but this may mean that there is something about experiencing psychosis itself that causes aging to accelerate. There are many possibilities for why that could be. For example, it is possible that psychosis causes people to wind up with more unhealthy lifestyles and that these unhealthy lifestyles are what cause faster aging. However, testing this hypothesis will require more research, especially longitudinal research.

PT: What do you hope the future of research on aging in schizophrenia looks like?

Whitman: First, I hope that researchers test whether there are specific factors that explain the link between schizophrenia and accelerated aging. For example, although we did not find that our results were not fully explained by tobacco smoking or antipsychotic medicine, there are many other lifestyle factors that we did not test. I would hope that future research can test whether things like social isolation, poverty, substance use, or poor diet help explain the link between schizophrenia and accelerated aging. Likewise, I hope that researchers continue to study whether certain genes linked to schizophrenia might also cause age-related diseases. These types of studies will help us better understand the mechanism that links schizophrenia and accelerated aging.

Furthermore, I hope that clinical trials of psychosis treatments include measures of aging as secondary outcomes. These measures of aging could be from brain MRI, like we did in our study, or epigenetic measures from blood. It would be fascinating to see whether interventions that treat psychosis have any effect on patients’ aging. If so, that would add more evidence to the hypothesis that psychosis causes faster aging. More importantly, it would also suggest that early and effective treatment of psychosis might contribute to reducing long-term risk for age-related diseases.

Mr Whitman is a clinical psychology PhD candidate at Duke University.

References

1. Whitman ET, Passiatore R, Knodt AR, et al. Replicated evidence for an accelerated rate of whole-body aging in schizophrenia. Psychol Med. 2026;56:e42.

2. Brendel RW, Stern TA. Psychotic symptoms in the elderly. Prim Care Companion J Clin Psychiatry. 2005;7(5):238-41.

3. Fischer CE, Aguera-Ortiz L, Mortby ME, et al. Psychosis and dementia: risk factor, prodrome, or cause? Intl Psychoger.2018;30(2):209-219.

4. Caspi A, Shireby G, Mill J et al. Accelerated pace of aging in schizophrenia: five case-control studies. Bio Psych. 2024;95(11):1038-1047.