Insulin resistance takes center stage: a new paradigm in the progression of bipolar disorder
Bibliographic record
Abstract
Bipolar Disorder (BD) is a major psychiatric illness affecting up to 5% of the population. BD can progress over time to a chronic “neuroprogressive” course with cognitive and functional impairment. Currently, there are no validated predictors indicating which patients will develop a neuroprogressive course and there are no specific treatments.This review presents data supporting a novel hypothesis on the mechanisms underlying bipolar neuroprogression. Insulin resistance (IR) is present in 52% of BD patients and is associated with chronic course, treatment nonresponse, adverse brain changes and cognitive impairment. Further, bipolar morbidity increases 12-fold following the onset of IR indicating that IR may modify disease progression. I review evidence that IR is a testable and treatable modifying factor in neuroprogression and that reversing IR may be an efficient (and perhaps the only) means of obtaining remission in some patients. I draw a parallel with Helicobacter pylori in peptic ulcer disease (a novel mechanism that brought together two previously unrelated phenomena that uncovered a new treatment approach).This model of bipolar progression combines shared dysregulated mechanisms between IR and BD, allowing for early screening, case finding, and monitoring for neuroprogression, with the potential for intervention that could prevent advanced bipolar illness.KEY MESSAGESNeuroprogression in bipolar disorder is defined by a more severe form of illness and poor outcome. Currently, there are no validated predictors of neuroprogression, which could help inform treatment and improve prognosis.Insulin resistance is present in more than half of all bipolar patients and is associated with a chronic course of illness, lack of response to mood stabilizing treatment, cognitive impairment and poor functional outcomes.Insulin resistance may modify the course of bipolar disorder and promote neuroprogression. Insulin resistance may be a testable and potentially modifiable risk factor for neuroprogression in bipolar disorder.
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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 | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.003 | 0.005 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.007 |
| Insufficient payload (model declined to judge) | 0.002 | 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".