Psychological stress and vulnerability for Major Depressive Disorder: cortisol, brain structure, function, and cognitive processing in young adults
Bibliographic record
Abstract
Psychological stress has an important impact on one's physical and mental health. Activation of the hypothalamic-pituitary-adrenal (HPA) stress axis and the subsequent increase in the stress hormone cortisol constitutes the organism's main response to stress. Individual differences in stress response contribute to one's vulnerability and resilience to a host of physical and psychological ills. Understanding the regulatory networks underlying stress processing in both healthy and vulnerable populations is essential. The work presented in this thesis aimed to investigate neural correlates of psychological stress processing and the HPA axis function in samples of healthy individuals as well as those with distinct vulnerability to a stress-related illness, Major Depressive Disorder. Our literature review revealed that only studies using serial subtraction or the Montreal Imaging Stress Task (MIST), a task that combines mental arithmetic and negative social evaluation components, were able to induce a significant cortisol stress response. Deactivation in orbitofrontal regions and the limbic system were most consistently observed in response to psychological stress. Exposing healthy subjects to a new, event-related version of MIST revealed that reduction of brain activity in the limbic system observed previously was specifically associated with the processing of social evaluative threat, a key component of psychological stress. We then examined HPA axis function (both basal and reactive) and the HPA regulatory brain areas for evidence of dysregulation in a sample of healthy young adults who showed varying levels of depressive tendencies, but at subclinical levels. This was the first time that these concepts were assessed in a subclinically depressed population. The subjects with increased subclinical levels of depression showed impairments in HPA function (in a form of blunted cortisol awakening response and blunted stress response), as well as impairment in certain key regions within the HPA axis regulatory network (for e.g. small hippocampal volumes and dysregulated medial orbitofrontal cortex). I conclude the thesis by proposing a basic model of a neural network underlying stress processing in a healthy population, and also outline nodes at which this network might be affected in subclinically depressed populations. Some research avenues for future studies are also highlighted.
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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 | 0.000 |
| 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".