Replicated evidence for an accelerated rate of whole-body aging in schizophrenia.

People with schizophrenia showed consistently faster whole-body aging pace compared to controls across four independent neuroimaging datasets.

• The study utilized DunedinPACNI, a novel neuroimaging biomarker of the longitudinal pace of aging, across four datasets with total N = 2,096 (48% female).
• Datasets were accessed through the Lieber Institute for Brain Development, the University of Bari Aldo Moro, and the North American Prodrome Longitudinal Study - 3 (NAPLS-3).
• The finding was described as 'consistent evidence of faster DunedinPACNI in schizophrenia compared with controls' across all four datasets.
• The replication across multiple independent cohorts strengthens the conclusion that accelerated aging is a feature of schizophrenia.

Youth at clinical-high risk for psychosis did not show faster whole-body aging pace compared to controls.

• Clinical-high risk (CHR) participants were drawn from the NAPLS-3 dataset.
• DunedinPACNI was not faster in CHR youth relative to controls, suggesting accelerated aging may not precede the onset of frank psychosis.
• This finding contrasts with the pattern observed in individuals with established schizophrenia diagnoses.
• The result suggests accelerated aging in schizophrenia is not simply a prodromal feature of the illness.

Unaffected siblings of patients with schizophrenia did not show faster whole-body aging pace compared to controls.

• Unaffected siblings were included in the analyses to test whether accelerated aging reflects familial (genetic or shared environmental) risk for schizophrenia.
• DunedinPACNI in unaffected siblings was not significantly faster than in controls.
• This finding suggests that the accelerated aging observed in schizophrenia is not primarily attributable to familial risk factors.
• The result is described as 'inconsistent with some of the most obvious explanations for accelerated aging in schizophrenia' including familial risk.

Tobacco smoking did not explain the faster pace of aging observed in people with schizophrenia.

• Tobacco smoking is highly prevalent in schizophrenia and is a known accelerant of biological aging, making it a plausible confound.
• Analyses controlled for or examined tobacco smoking as a potential explanation for faster DunedinPACNI in schizophrenia.
• Faster DunedinPACNI in schizophrenia was 'not explained by tobacco smoking,' per the authors' conclusion.
• This finding indicates that the accelerated aging signal in schizophrenia is independent of smoking behavior.

Antipsychotic medication use did not explain the faster pace of aging observed in people with schizophrenia.

• Antipsychotic medications are a standard treatment for schizophrenia and represent a potential iatrogenic explanation for accelerated aging.
• Analyses examined antipsychotic medication use as a potential confounder of the DunedinPACNI findings.
• Faster DunedinPACNI in schizophrenia was 'not explained by antipsychotic medication use,' according to the authors.
• The result argues against an iatrogenic medication effect as the primary driver of accelerated aging in this population.

DunedinPACNI was used as a neuroimaging-based biomarker to measure the pace of whole-body aging in schizophrenia samples.

• DunedinPACNI is described as 'a novel neuroimaging biomarker of the longitudinal pace of aging.'
• The biomarker was specifically chosen because of the 'limited ability to measure aging in samples of people with schizophrenia' using prior methods.
• The neuroimaging approach enabled testing the accelerated aging hypothesis across multiple existing datasets totaling 2,096 participants.
• DunedinPACNI is derived from brain imaging data and is designed to capture whole-body, not just brain-specific, aging.

People with schizophrenia are known to develop more chronic diseases at younger ages and die younger than the general population, motivating the accelerated aging hypothesis.

• Excess morbidity and mortality in schizophrenia 'could be partially due to accelerated aging in schizophrenia,' according to the authors.
• The authors note this excess morbidity and mortality motivates the development of 'gero-protective' interventions.
• Prior difficulty testing the accelerated aging hypothesis was attributed 'in part, due to the limited ability to measure aging in samples of people with schizophrenia.'
• The study was framed as providing an opportunity to rigorously test the accelerated aging hypothesis using a validated neuroimaging biomarker.