P4‐248: EVALUATING SHARED GENETIC LIABILITY FOR LATE‐LIFE ABNORMAL THOUGHTS AND PERCEPTION (MILD BEHAVIORAL IMPAIRMENT), AND NEUROLOGICAL AND PSYCHIATRIC CONDITIONS
Bibliographic record
Abstract
Mild Behavioral Impairment (MBI) is a neurobehavioral syndrome characterized by often subtle neuropsychiatric changes which emerge later in life and are not attributable to preexisting psychiatric conditions. MBI is associated with an increased risk of dementia both in the context of MCI and in cognitively normal older adults. The emergence of subtle changes to thoughts (e.g. persecutory delusions) and perception (e.g. visual hallucinations) in cognitively normal older adults is a particularly interesting cluster of MBI symptoms. However, whether and to what extent they represent a prodromal neurodegenerative disease state is unknown. In this exploratory analysis we examine whether these ‘symptoms’ in the cognitively normal population are genetically related to major depressive disorder (MDD), schizophrenia (SCZ) and Alzheimer's disease (AD). Abnormal thoughts and perception were rated using the Mild Behavioral Impairment Checklist (MBI-C) in a sample of 3,152 PROTECT study participants who had also provided a DNA sample. Publicly available summary statistics for MDD, SCZ and Alzheimer's disease were used for genetic comparisons. Polygenic risk scores were generated for AD, MDD and SCZ and tested for association with the MBI-C ratings. LD Score Regression was used to estimate the genetic correlation between each clinical condition and MBI-C ratings. 123 people reported having abnormal thoughts and perception items as rated by the MBI-C. There was a significant association between abnormal thoughts and perception and schizophrenia polygenic score (OR 1.4[95% CI: 1.15-1.65], p=0.0005, R=0.015) and there was modest evidence of genetic correlation between these two phenotypes (rg=0.22, p=0.08). There was no evidence of association in any of the other comparisons. These findings suggest that, while associated with higher risk of conversion to dementia in clinical populations, the genetic etiology of abnormal thoughts and perception in preclinical populations is more closely related to schizophrenia than Alzheimer's disease. This study is a relatively small sample and more data will be needed to confirm these findings, particularly for the LD score regression.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".