ArticleBiological psychiatry2010
Mood disorder susceptibility gene CACNA1C modifies mood-related behaviors in mice and interacts with sex to influence behavior in mice and diagnosis in humans.
Article in Biological psychiatry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- A Systematic Review of Genetic Polymorphisms Associated with Bipolar Disorder Comorbid to Substance Abuse.Genes · 2022Pooled it
- A Genome-Wide Association Study of Premenstrual Symptoms in Two Nordic Populations.Biological psychiatry global open science · 2026Article
- Ionic Homeostasis Failure in Major Depressive Disorder: Ion Channel Mechanisms, Excitation-Inhibition Imbalance, and Precision Therapeutics.International journal of molecular sciences · 2026Review
- Deletion ofFrontiers in cellular neuroscience · 2026Article
- Deletion ofbioRxiv : the preprint server for biology · 2025Article
- Reduced Gene Dosage of the Psychiatric Risk GeneInternational journal of molecular sciences · 2025Article
- miR-708-5p is elevated in bipolar patients and can induce mood disorder-associated behavior in mice.EMBO reports · 2025Article
- 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
- Sex-Specific Mechanisms Underlie Long-Term Potentiation at Hippocampus→Medium Spiny Neuron Synapses in the Medial Shell of the Nucleus Accumbens.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Natural L-type calcium channels antagonists from Chinese medicine.Chinese medicine · 2024Article
- Unlocking Neural Function with 3D In Vitro Models: A Technical Review of Self-Assembled, Guided, and Bioprinted Brain Organoids and Their Applications in the Study of Neurodevelopmental and Neurodegenerative Disorders.International journal of molecular sciences · 2023Review
- Connecting Dots between Mitochondrial Dysfunction and Depression.Biomolecules · 2023Review
- L-type calcium channel regulation of dopamine activity in the ventral tegmental area to nucleus accumbens pathway: Implications for substance use, mood disorders and co-morbidities.Neuropharmacology · 2023Review
- Temperament traits mediate the relationship between CACNA1C polymorphisms and bipolar disorder in cisgender women.European archives of psychiatry and clinical neuroscience · 2023Article
- CACNA1C-Related Channelopathies.Handbook of experimental pharmacology · 2023Review
- The neural basis underlying female vulnerability to depressive disorders.Animal cells and systems · 2023Review
- Wildtype peers rescue social play and 50-kHz ultrasonic vocalization deficits in juvenile femaleFrontiers in behavioral neuroscience · 2023Article
- The Wistar Kyoto Rat: A Model of Depression Traits.Current neuropharmacology · 2023Article
- BDNF Levels According to Variations in the CACNA1C Gene: Sex-Based Disparity.Cellular and molecular neurobiology · 2023Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundRecent genome-wide association studies have associated polymorphisms in the gene CACNA1C, which codes for Ca(v)1.2, with a bipolar disorder and depression diagnosis.
methodsThe behaviors of wild-type and Cacna1c heterozygous mice of both sexes were evaluated in a number of tests. Based upon sex differences in our mouse data, we assessed a gene × sex interaction for diagnosis of mood disorders in human subjects. Data from the National Institute of Mental Health Genetics Initiative Bipolar Disorder Consortium and the Genetics of Recurrent Early-Onset Major Depression Consortium were examined using a combined dataset that included 2021 mood disorder cases (1223 female cases) and 1840 control subjects (837 female subjects).
resultsIn both male and female mice, Cacna1c haploinsufficiency was associated with lower exploratory behavior, decreased response to amphetamine, and antidepressant-like behavior in the forced swim and tail suspension tests. Female, but not male, heterozygous mice displayed decreased risk-taking behavior or increased anxiety in multiple tests, greater attenuation of amphetamine-induced hyperlocomotion, decreased development of learned helplessness, and a decreased acoustic startle response, indicating a sex-specific role of Cacna1c. In humans, sex-specific genetic association was seen for two intronic single nucleotide polymorphisms, rs2370419 and rs2470411, in CACNA1C, with effects in female subjects (odds ratio = 1.64, 1.32) but not in male subjects (odds ratio = .82, .86). The interactions by sex were significant after correction for testing 190 single nucleotide polymorphisms (p = 1.4 × 10⁻⁴, 2.1 × 10⁻⁴; p(corrected) = .03, .04) and were consistent across two large datasets.
conclusionsOur preclinical results support a role for CACNA1C in mood disorder pathophysiology, and the combination of human genetic and preclinical data support an interaction between sex and genotype.
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