Metabolic plasticity: an evolutionary perspective on metabolic and circadian dysregulation in bipolar disorder
Bibliographic record
Abstract
The emerging field of metabolic psychiatry has brought mechanisms of metabolic dysfunction into focus in bipolar disorder research. In this manuscript, we propose that the metabolic features of bipolar disorder provide a new vector from which to understand the role of circadian dysfunction in this condition. A notable feature of bipolar disorder is the photoperiod driven, seasonal occurrence of symptoms and episodes mediated by circadian systems, with mania occurring more frequently in the spring and autumn at times of rapid rate of change in photoperiod, and depression being more prevalent in the winter when photoperiod is attenuated. In this manuscript we note that seasonal adaptations in metabolism are highly conserved evolutionary traits across diverse taxa. Several of the underlying mechanisms mediating seasonal changes in metabolism are conserved in human biology and are implicated in bipolar disorder pathophysiology. Such mechanisms encompass targets of lithium involved in insulin signaling (the phosphatidylinositol cycle, GSK3β and Akt), clock genes (CLOCK and BMAL1), targets of psychiatric and metabolic medications (mTOR and AMPK) and hormonal signaling (melatonin and cortisol). We propose that bipolar disorder may represent a dysregulation of conserved mechanisms of chronometabolic regulation and provide a discussion of the evolutionary context of such mechanisms. Genetic predisposition coupled to novel environmental inputs to human biology including artificial light at night and sustained refined sugar and carbohydrate intake may contribute to states of metabolic and circadian dysregulation in bipolar disorder underlying episodes of mania and depression.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".