The Role of Serotonin Transporter Protein Gene in Antidepressant-Induced Mania in Bipolar Disorder
Bibliographic record
Abstract
BACKGROUND: The occurrence of mania during antidepressant treatment is a key issue in the clinical management of bipolar disorder (BP). The serotonin transporter (5-HTT) is the selective site of action of most proserotonergic compounds used to treat bipolar depression. The 5-HTT gene (SLC6A4) has 2 known polymorphisms. The aim of this study was to investigate the role of the SLC6A4 variants in the pathogenesis of antidepressant-induced mania in BP. METHODS: Twenty-seven patients with a DSM-IV diagnosis of BP I or II, with at least 1 manic or hypomanic episode induced by treatment with proserotonergic antidepressants (IM+ group), were compared with 29 unrelated, matched patients with a diagnosis of BP I or II, who had been exposed to proserotonergic antidepressants without development of manic or hypomanic symptoms (IM- group). The 2 known polymorphisms of the SLC6A4 were genotyped, and allelic and genotypic association analyses were performed. RESULTS: With respect to the polymorphism in the promoter region (5HTTLPR), IM+ patients had an excess of the short allele (n = 34 [63%]) compared with IM- patients (n = 17 [29%]) (chi(2)(1), 12.77; P <.001). The genotypic association analysis showed a higher rate of homozygosity for the short variant in the IM+ group (n = 10 [37%]) than in the IM- group (n = 2 [7%]) and a lower rate of homozygosity for the long variant in the IM+ group (n = 3 [11%]) compared with the IM- group (n = 14 [48%]) (chi(2)(2), 12.43; P =.002). No associations were found for the polymorphism involving a variable number of tandem repeats. CONCLUSION: If these results are replicated, the 5HTTLPR polymorphism may become an important predictor of abnormal response to medication in patients with BP.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".