Genotype over diagnosis in amygdala responsiveness: affective processing in social anxiety disorder
Bibliographic record
Abstract
Background: Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)–related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 ( TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls. Methods: We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms. Results: Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles. Limitations: Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrolment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli. Conclusion: Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT–related genes into account.
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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 | 0.001 | 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) | 0.003 | 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".