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Record W2005567293 · doi:10.1176/pn.43.19.0018a

Gene Study Reveals Clues to Bipolar Disorder Physiology

2008· article· en· W2005567293 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

aboutThe title or abstract carries a Canadian signal from the geographic lexicon.
no affNo Canadian affiliation: this work is invisible to an affiliation-only frame.
No Canadian affiliation. An affiliation-only frame, the usual design, would never have seen this work. It is one of the works that make the case for inverting the frame.

Bibliographic record

VenuePsychiatric News · 2008
Typearticle
Languageen
FieldMedicine
TopicBipolar Disorder and Treatment
Canadian institutionsnot available
Fundersnot available
KeywordsIon channelBipolar disorderSodium channelAnkyrinSodiumCalciumCalcium channelNeuroscienceGeneBiologyChemistryGeneticsMedicineInternal medicineCognition

Abstract

fetched live from OpenAlex

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<www.nature.com/ng/journal/v40/n9/abs/ng.209.html>.▪ ISSUES NewArchived

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.066
Threshold uncertainty score0.832

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.001

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.

Opus teacher head0.020
GPT teacher head0.291
Teacher spread0.271 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it