Probing the Biological Underpinnings of Advanced Brain Ageing in Schizophrenia
Bibliographic record
Abstract
Background Recent evidence suggests that patients with schizophrenia may show advanced brain ageing, particularly evident after the first year of onset. However, it is unclear if accelerated ageing relents, persists or continues to increase over time. The underlying causal factors are also poorly understood. Disruptions in glutamate function, oxidative stress, and inflammation may all contribute to progressive brain changes in people with schizophrenia. We examine whether brain ageing differs between early and established stages of schizophrenia, correlates with symptom severity and varies with markers of brain function, oxidative status and inflammatory burden. Methods Two brain-age prediction models assessed 112 participants (34 recent onset psychosis, 36 established schizophrenia, 42 healthy controls). Brain age gap (BAG) was calculated by subtracting chronological age from predicted age. Shapley’s additive explanations (SHAP) identified influential structural magnetic resonance imaging (MRI) features driving brain-age prediction. Linear regression models and partial correlations, adjusting for age, explored associations between BAG and neurometabolites, inflammatory markers, medication exposure and clinical scores in the whole sample. Results The established schizophrenia group showed higher BAG (Mean = 6.21, SD = 7.30) compared to healthy individuals (Mean = -0.01, SD = 9.10), while recent-onset patients (Mean = 4.23, SD = 9.25) did not differ significantly from healthy individuals. The top 10 SHAP features diving the BAG included ventricular enlargement and total grey matter volume, which was similar in psychosis to healthy individuals. In a combined psychosis group (established + recent-onset), higher BAG correlated with more severe symptoms (PANSS total, general, and anxiodepressive subscales). BAG positively associated with Magnetic Resonance Spectroscopy measured glutathione and negatively with N-Acetyl Aspartate. Discussion Accelerated brain age in schizophrenia may be related to illness severity and poor defence against oxidative stress. The lack of differences in SHAP features between schizophrenia and healthy individuals suggests that the pattern of brain ageing is in keeping with advanced normal ageing. Findings suggest potential treatment targets to improve brain health in schizophrenia, warranting further research.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".