Interrelations between dopaminergic-, gabaergic- and glutamatergic neurotransmitters in antipsychotic-naïve psychosis patients and the association to initial treatment response
Bibliographic record
Abstract
Abstract Preclinical evidence points to disturbances in neural networks in psychosis involving interrelations between dopaminergic-, GABAergic- and glutamatergic neurotransmitter systems. In support, we have previously shown that aberrant interrelations between these neurotransmitters, in contrast to individual transmitter systems, can separate antipsychotic-naïve first-episode psychotic patients (AN-FEP) from healthy controls (HC). Here, we characterized neurotransmitter interrelations, examined their association with treatment response, and explored the effect of treatment on the interrelations. Sixty participants (29 AN-FEP and 31 HC) underwent dynamic [18F]-DOPA PET with arterial blood sampling to measure dopamine synthesis (DS) (k 3 ) in nucleus accumbens (NAcc) and magnetic resonance spectroscopy (MRS) to estimate levels of glutamate (Glu) in anterior cingulate cortex (ACC) and thalamus, and gamma-aminobutyric-acid (GABA) in ACC. A subgroup of the patients was re-scanned after six weeks antipsychotic monotherapy with aripiprazole (PET: 10 AN-FEP; MRS: 27 AN-FEP; 30 HC). Psychopathology was assessed at both visits. Multiple linear regression models and linear mixed models were used to analyze data. We found a negative association between k 3 (dependent variable) and GABA in HC (β = −0.15, p = 0.03) and a positive association in patients (β = 0.15, p = 0.04). The aberrant relationship between k 3 and GABA was driven by the group-GABA interaction (p = 0.002) and related to treatment response (p = 0.02). No significant group interactions were found for the interrelations between k 3 and Glu, but a positive association was found between k 3 and Glu in thalamus (p = 0.04) in both groups and the association decreased after treatment in AN-FEP (p = 0.01). The data show that DS in NAcc and GABA levels in ACC are inversely interrelated in AN-FEP, and that the degree of abnormality predicts treatment effect. Moreover, antipsychotic treatment alters the relationship between dopaminergic activity in NAcc and Glu levels in thalamus. The findings suggest that combined instead of single neurotransmitter disturbances should be considered when novel therapeutics are developed for schizophrenia. Clinical trial registration: The Pan European Collaboration on Antipsychotic Naïve Schizophrenia II (PECANSII) study, ClinicalTrials.gov Identifier: NCT02339844. https://www.clinicaltrials.gov/study/NCT02339844 .
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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 | 0.002 |
| 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 | 0.001 | 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".