Mitochondrial Complex I Activity and Oxidative Damage to Mitochondrial Proteins in the Prefrontal Cortex of Patients With Bipolar Disorder
Bibliographic record
Abstract
CONTEXT: Accumulating evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of bipolar disorder and schizophrenia. It remains unclear whether mitochondrial dysfunction, specifically complex I impairment, is associated with increased oxidative damage and, if so, whether this relationship is specific to bipolar disorder. OBJECTIVE: To evaluate whether decreased levels of the electron transport chain complex I subunit NDUFS7 are associated with complex I activity and increased oxidative damage to mitochondrial proteins in the prefrontal cortex of patients with bipolar disorder, schizophrenia, or major depressive disorder. DESIGN: Postmortem prefrontal cortex from patients and controls were assessed using immunoblotting, spectrophotometric, competitive enzyme immunoassay to identify group differences in expression and activity of complex I, and in oxidative damage in mitochondria. SETTING: University of British Columbia, Vancouver, Canada. Patients Forty-five patients with a psychiatric disorder (15 each with bipolar disorder, schizophrenia, and major depressive disorder) and 15 nonpsychiatric control subjects were studied. MAIN OUTCOME MEASURES: Oxidative damage to proteins and mitochondrial complex I activity. RESULTS: Levels of NDUFS7 and complex I activity were decreased significantly in patients with bipolar disorder but were unchanged in those with depression and schizophrenia compared with controls. Protein oxidation, as measured by protein carbonylation, was increased significantly in the bipolar group but not in the depressed or schizophrenic groups compared with controls. We observed increased levels of 3-nitrotyrosine in the bipolar disorder and schizophrenia groups. CONCLUSIONS: Impairment of complex I may be associated with increased protein oxidation and nitration in the prefrontal cortex of patients with bipolar disorder. Therefore, complex I activity and mitochondrial dysfunction may be potential therapeutic targets for 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 | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".