When an older brain is to blame
People suffering from SZ can expect to live 15 years fewer than they ordinarily would. A new study supported in part by the EU-funded EarlyCause project has now found that this could be partly caused by advanced brain ageing. The research findings were published in the journal ‘Molecular Psychiatry’. SZ is associated with an increased risk of premature death, partially as a result of suicide or poor physical health. Studies to date have suggested that the high prevalence of disease, long-term cognitive decline and excess deaths in people with SZ could in part be caused when their brain’s biological age overtakes the chronological age. According to a few small-scale studies, this discrepancy called brain-predicted age difference (brain-PAD) has been found to be consistently higher in schizophrenic patients compared to healthy individuals. The studies have also shown that the gap between the two ages mainly widens during the first years after the onset of the illness.
On a larger scale
Recognising the importance of examining whether these findings can be generalised through large-scale studies, the research team investigated brain age in over 5 000 individuals from 26 international cohorts from the Enhancing NeuroImaging Genetics through Meta-Analysis [ENIGMA] Schizophrenia working group. The study included data from 2 803 schizophrenic patients and 2 598 healthy individuals aged 18 to 73 years. “Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans,” the study reports. On average, people with SZ were found to have a higher brain-PAD compared to healthy controls, with a discrepancy between their brain-predicted age and their chronological age being about 3.5 years bigger. The team also investigated whether a higher brain-PAD in schizophrenic patients was linked to specific clinical characteristics: the age of onset of the illness, how long the patient has had SZ, the severity of the symptoms, and the use and dosage of antipsychotic drugs. They found no association between brain-PAD and these characteristics. “This suggests that a greater brain-PAD in SZ may not be primarily driven by disease progression or treatment-related effects on brain structure that have been reported elsewhere. This is in keeping with previous studies showing a greater brain-PAD already present in first-episode SZ and first-episode psychosis patients,” the authors state. The study concludes that longitudinal studies with more in-depth clinical characterisation are needed to establish whether a brain-age predictor such as brain-PAD could be a useful tool in early prevention or intervention strategies for the disease. In addition to funding from EarlyCause (Causative mechanisms & integrative models linking early-life-stress to psycho-cardio-metabolic multi-morbidity), the study also received EU support through the data contributed by a number of cohort studies backed by other EU-funded projects. EarlyCause ends in December 2023. For more information, please see: EarlyCause project website
Keywords
EarlyCause, brain, age, schizophrenia, brain-predicted age difference, disease