ArticleBiological psychiatry2013
The ANK3 bipolar disorder gene regulates psychiatric-related behaviors that are modulated by lithium and stress.
Article in Biological psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 111 citations in OpenAlex.
- Explore the Mechanism of Xiaoyaosan for Treatment of Bipolar Disorder Based on Network Pharmacology, Experimental Validation and Molecular Docking.CNS neuroscience & therapeutics · 2026Article
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- Genomic structural equation modeling reveals the shared genetic architecture of osteosarcopenia across five musculoskeletal phenotypes.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Axon initial segment structure and function in health and disease.Physiological reviews · 2025Review
- Novel ABCD1 and MTHFSD Variants in Taiwanese Bipolar Disorder: A Genetic Association Study.Medicina (Kaunas, Lithuania) · 2025Article
- An increased copy number of glycine decarboxylase (GLDC) associated with psychosis reduces extracellular glycine and impairs NMDA receptor function.Molecular psychiatry · 2025Article
- Construction and Brain Validation of circRNAs-miRNAs-mRNAs Regulatory Axis in Early-Onset Schizophrenia.Neuropsychiatric disease and treatment · 2025Article
- Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.Nature communications · 2024Article
- NEK4 modulates circadian fluctuations of emotional behaviors and synaptogenesis in male mice.Nature communications · 2024Article
- Progress and Implications from Genetic Studies of Bipolar Disorder.Neuroscience bulletin · 2024Review
- Age-dependent regulation of axoglial interactions and behavior by oligodendrocyte AnkyrinG.bioRxiv : the preprint server for biology · 2024Article
- Abnormal patterns of sleep and waking behaviors are accompanied by neocortical oscillation disturbances in an Ank3 mouse model of epilepsy-bipolar disorder comorbidity.Translational psychiatry · 2023Article
- A characteristic cerebellar biosignature for bipolar disorder, identified with fully automatic machine learning.IBRO neuroscience reports · 2023Article
- Expression of ANK3 moderates the association between childhood trauma and affective traits in severe mental disorders.Scientific reports · 2023Article
- Lithium rescues dendritic abnormalities in Ank3 deficiency models through the synergic effects of GSK3β and cyclic AMP signaling pathways.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome.Molecular psychiatry · 2023Article
- Personality traits as mediators in the association betweenFrontiers in psychiatry · 2023Article
- Palmitoylation controls the stability of 190 kDa ankyrin-G in dendritic spines and is regulated by ZDHHC8 and lithium.Frontiers in molecular neuroscience · 2023Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnkyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown.
methodsTo gain insight into the potential disease relevance of ANK3, we examined the function of mouse Ank3 in the regulation of psychiatric-related behaviors using genetic, neurobiological, pharmacological, and gene-environment interaction (G×E) approaches. Ank3 expression was reduced in mouse brain either by viral-mediated RNA interference or through disruption of brain-specific Ank3 in a heterozygous knockout mouse.
resultsRNA interference of Ank3 in hippocampus dentate gyrus induced a highly specific and consistent phenotype marked by decreased anxiety-related behaviors and increased activity during the light phase, which were attenuated by chronic treatment with the mood stabilizer lithium. Similar behavioral alterations of reduced anxiety and increased motivation for reward were also exhibited by Ank3+/- heterozygous mice compared with wild-type Ank3+/+ mice. Remarkably, the behavioral traits of Ank3+/- mice transitioned to depression-related features after chronic stress, a trigger of mood episodes in BD. Ank3+/- mice also exhibited elevated serum corticosterone, suggesting that reduced Ank3 expression is associated with elevated stress reactivity.
conclusionsThis study defines a new role for Ank3 in the regulation of psychiatric-related behaviors and stress reactivity that lends support for its involvement in BD and establishes a general framework for determining the disease relevance of genes implicated by patient genome-wide association studies.
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