Bibliographic record
Abstract
Back to table of contents Previous article Next article Clinical & Research NewsFull AccessGene Study Reveals Clues to Bipolar Disorder PhysiologyJun YanJun YanSearch for more papers by this authorPublished Online:3 Oct 2008https://doi.org/10.1176/pn.43.19.0018aA large genomic study suggests that defective sodium and calcium channels in neurons may explain an important part of the physiological mechanism of bipolar disorder.A group of researchers in the United States, United Kingdom, and Canada found significant association between bipolar disorder and genetic variations in two genes involved in the formation of a sodium channel and a calcium channel, ANK3 and CACNA1C.The study, the largest genomic study on bipolar disorder to date, tested 1.8 million genetic polymorphisms in 4,387 bipolar patients and 6,209 control subjects from three studies to identify genetic variations that may be significantly associated with the illness.Sodium and calcium channels are “ion gates” made of proteins embedded in cell membranes. They regulate the amount of electrically charged sodium and calcium ions flowing in and out of nerve cells as they open and close. This process is a fundamental part of generating and transmitting signals throughout the nervous system.The ANK3 gene is expressed as the ankyrin G protein, a type of protein involved in regulating the sodium channels in nerve cell membranes that open and close according to electrical impulses. They are known as voltage-gated channels because they open and close depending on the difference in electric charges within and outside of the cell membrane. Several single nucleotide polymorphisms across the chromosomal region for the ANK3 gene were found to be strongly associated with bipolar disorder (p=9.1×10-9), meaning that bipolar patients are much more likely to have defects in this protein than those with-out the illness.The second strongest genetic association with the illness was found in a noncoding region (the third intron) of the CACNA1C gene, which codes for a subunit of the L-type voltage-gated calcium channel protein. Additional regions associated with bipolar disorder were also identified.Scientists have already suspected ion channel problems in the mechanism of bipolar disorder, as both ANK3 and subunits of the calcium channel are downregulated in the brain in mice after lithium treatment. The findings in this genomic study have provided strong and independent corroboration for this theory.The study was published online in Nature Genetics on August 17 and supported by grants from a number of government agencies in the United States, Australia, the United Kingdom, and Ireland and several private sources.An abstract of “Collaborative Genome-wide Association Analysis Supports a Role for ANK3 and CACNA1C in Bipolar Disorder” is posted at .▪ ISSUES NewArchived
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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 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.123 | 0.040 |
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".