Summaries from the XIX world congress of psychiatric genetics, Washington, DC, September 10–14, 2011
Bibliographic record
Abstract
Suicide is strongly associated with Major Affective Disorders with a risk for completed suicide 6 to 15 times higher in patients compared to the general population. Lithium is to date the most effective treatment for bipolar disorder (BD) with a well established protective effect against suicide. However, the mechanisms responsible for these clinical effects remain unclear. So far, several studies attempted to identify biological markers and genes involved in suicide. A gene expression microarray study performed using postmortem brain tissue by Sequeira et al. (2006) reported a significant reduction in expression of the gene encoding the enzyme spermidine/spermine N1-acetyltransferase 1 (SSAT1) in suicide completers with and without depression compared to controls. This result has been replicated by others. \nTo confirm and extend these findings, we measured SSAT1 gene expression levels in lymphoblastoid cell lines (LCLs) from two populations (Sardinian, n = 41 and Canadian, n = 24) of BD subjects characterized for suicidal behaviour and healthy controls. In order to test the effect of lithium on SSAT1, each LCL was divided into two lines cultured for 7 days in media with and without LiCl (1.0 mmol/l). \nSSAT1 expression was significantly increased by lithium in LCLs from controls (p< 0.001) and in subjects with low (p < 0.001) and high (p < 0.001) personal and genetic risk of suicide but not in LCLs from suicide completers (p > 0.05). These findings were replicated in the Canadian sample and the analysis on the pooled dataset increased the power and the significance of our findings. In contrast with the gene expression findings the protein study showed that SSAT1 levels were significantly decreased when comparing each of the 3 groups at different risk of suicide with controls. This could suggest a compensatory effect in the pathway of polyamine system. These differences were reduced or disappeared by lithium treatment in vitro. On the other hand, no differences were shown when comparing groups with different risk of suicide either with or without lithium treatment in vitro. The proteome analysis also highlighted several proteins differentially expressed in at least one of the comparisons or according to lithium treatment. These proteins are currently being identified and results will be presented at the conference. In conclusion, our findings suggest that suicide completers might represent a distinct group of patients with an altered SSAT1 function.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.269 | 0.151 |
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".