Molecular Abnormalities in Postmortem Brains of Subjects with Mood Disorders
Bibliographic record
Abstract
Biochemical and structural abnormalities have been reported in postmortem brain tissue from patients with mood disorders. Studies of the molecular pharmacology of drugs used in the treatment of mood disorders have led to a reinterpretation of earlier models of neuropathology in these diseases. Noradrenergic and serotonergic hypotheses have been expanded to include postsynaptic intracellular signal transduction pathways, regulation of gene expression, and synaptic plasticity. Because much of this evidence was obtained from postmortem brain, the experiments in this study also used postmortem tissue to examine the neuropathology of mood disorders. Human postmortem brain tissue was obtained from the Stanley Consortium Neuropathology Foundation and consisted of pieces of temporal and occipital cortex, and slices of prefrontal cortex and hippocampus from patients with bipolar affective disorder (BD), major depressive disorder (MDD), schizophrenia (SCZ) and controls (N = 15 per group). Components of the cAMP system were examined, as were potential target transcription and neurotrophic factors. Morphological consequences arising from altered cAMP signalling such as sprouting and DNA fragmentation were also investigated. There was a trend towards blunted temporal cortex adenylyl cyclase activity in subjects with mood disorders, and decreased occipital cortex Gas in lithium-treated BD subjects. Temporal cortex CREB level~ were decreased in antidepressant-untreated MDD subjects compared to controls, and normal in those subjects treated by antidepressants at the time of death. Temporal cortex CREB levels were decreased in BD patients treated with anticonvulsants relative to those not treated by anticonvulsants at the time of death. When assessing the effect of suicide on cAMP signalling, subjects who died as a result of suicide had lower temporal cortex CREB levels and CRE-binding than subjects who died of other causes. This effect was most evident in the MDD group. In hippocampus, BDNF levels were increased in subjects treated by antidepressants compared to subjects not treated by these medications at the time of death. This finding was more pronounced in the MDD group. Hippocampal studies also showed that BD subjects had increased mossy fibre staining relative to controls and other diagnoses, suggesting increased sprouting of the dentate gyrus axons. These postmortem findings are consistent with recent animal and cell models of antidepressant and mood stabilizer pharmacology. The changes in post-receptor signalling and hippocampal sprouting are also consistent with current conceptualizations of the neurobiology of mood disorders. These studies support the use of postmortem brain tissue as a clinically relevant research model, and add to the growing literature elucidating the pathophysiology of mood disorders and the molecular pharmacology of their treatments.
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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 | 0.001 | 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) | 0.002 | 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".