What are the Recurring Theories Regarding the Pathogenesis of Major Depressive Disorder?
Bibliographic record
Abstract
Introduction: Several theories regarding the etiology of Major Depressive Disorder (MDD) provoke challenges in defining the exact pathology of the disorder. Among these theories, the most recurring theories were the monoamine hypothesis, cytokine hypothesis, and endocrine factors. Each of these hypotheses are backed with neurobiological studies and provide unique insight on the etiology of MDD. The current state of the literature of MDD is confusing and complex. There are various theories that explain the pathogenesis of MDD, each supported with evidence from pre-clinical and clinical studies. In this review, we aim to explain the most common theories of MDD and identify connections to the pathological mechanisms of this disease. Methods: A literature search considering inclusion/exclusion criteria was conducted to determine the different theories on the pathology of MDD and their limitations. Results: Using the inclusion/exclusion criteria, 44 articles were analyzed to form the basis of our review. Three main theories were found to be the most recurring, the monoamine hypothesis, cytokine hypothesis, and endocrine factors. Discussion: The monoamine hypothesis suggests that MDD is due to a deficiency of monoamines, specifically the hormone 5-HT, or serotonin. In contrast, the cytokine hypothesis proposes that the abnormal regulation of proinflammatory cytokines is linked to MDD through multiple facets. Finally, dysfunction of the hypothalamic–pituitary–adrenal axis is currently being studied as several papers have reported increased cortisol levels in patients with MDD, suggesting a relation between the two. Conclusion: This paper investigates the recurring theories regarding the pathogenesis of Major Depressive Disorder. However, further analysis revealed that the theories contain several inconsistencies that weaken their respective arguments. This includes unanticipated latency of drug effects, contradictory reports, and failed replications. Many argue that these hypotheses are not the cause of Major Depressive Disorder, but rather a concomitant occurrence. Major Depressive Disorder includes diverse symptoms with various external causes, a matter which makes it difficult to accurately define its pathology. Advanced neurobiological research enables easier diagnosis and the development of effective treatments used by clinicians. Consequently, it is imperative to have a thorough understanding of the pathologic process.
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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 | 0.010 | 0.025 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.009 | 0.008 |
| Science and technology studies | 0.001 | 0.003 |
| Scholarly communication | 0.004 | 0.007 |
| Open science | 0.002 | 0.002 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.002 | 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".