Mood Disorder Susceptibility Gene CACNA1C Modifies Mood-Related Behaviors in Mice and Interacts with Sex to Influence Behavior in Mice and Diagnosis in Humans

Dao, David; Mahon, Pamela B.; Cai, Xiang; Kovacsics, Colleen E.; Blackwell, Robert; Arad, Michal; Shi, Jianxin; Zandi, Peter P.; O’Donnell, Patricio; Knowles, James A.; Weissman, Myrna M.; Coryell, William; Scheftner, William A.; Lawson, William B.; Levinson, Douglas F.; Thompson, Scott M.; Potash, James B.; Gould, Todd D.

doi:10.1016/j.biopsych.2010.06.019

Cited by 165 publications

(179 citation statements)

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Section: Strength Of Evidencementioning

confidence: 99%

“…In another proposed model of bipolar disorder, the CACNA1c knockout mouse, female mice exhibit more robust attenuation of amphetamine-induced hyper-locomotion than male mice. Moreover, female, unlike male mice, display an attenuated acoustic startle response and reduced expression of learned helplessness, along with phenotypes of increased anxiety or decreased risk taking (Dao et al, 2010).In summary, several models of bipolar disorder have been proposed and used, but none of them convincingly simulates the alternating states of human mania and depression. Instead, separate paradigms are traditionally used for mania and depression.…”

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Sex differences in animal models of psychiatric disorders

Kokras

Dalla

2014

British J Pharmacology

359

187

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Psychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories. LINKED ARTICLESThis article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10. 1111/bph.2014.171.issue-20 Abbreviations 5-HTT, 5-HT transporter; 8-OH-DPAT, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol; Akt1, V-akt murine thymoma viral oncogene homologue 1; BDNF, brain-derived neurotrophic factor; BTBR, BTBR T + tf/J; CMS, chronic mild stress; COMT, catechol-O-methyltransferase-deficient mice; CR, conditioned response; CRF, corticotrophinreleasing factor; CS, conditioned stimulus; D1 receptor, dopamine 1 receptor; D2 receptor, dopamine 2 receptor; DISC1, disrupted-in-schizophrenia 1; Ehmt1, euchromatin histone methyltransferase 1; FBGRKO, forebrain glucocorticoid type II receptor (NR3C1) knockout; FSL, flinders sensitive rat line; FST, forced swim test; GSK3, glycogen synthase kinase 3; HAB, high anxiety-related behaviour rats; ICSS, intracranial self-stimulation; LAB, low anxiety-related behaviour rats; LI, latent inhibition; Mthfr, methylenetetrahydrofolate reductase; OCD, obsessive-compulsive disorder; PPI, prepulse inhibition; PTSD, post-traumatic stress disorder; SSRI, selective 5-HT re-uptake inhibitors; US, unconditioned stimulus; WKY, Wistar Kyoto IntroductionThe total disease burden for neuropsychiatric disorders in the European Union has been recently ...

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Section: Strength Of Evidencementioning

confidence: 99%

mentioning

confidence: 99%

Sex differences in animal models of psychiatric disorders

Kokras

Dalla

2014

British J Pharmacology

359

187

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“…Other recently described genetically engineered models for manic-like behavior involve manipulation of the genes DAT (dopamine transporter) [Young et al, 2010b], GRIN2A (NMDA receptor subunit 2A) [Taniguchi et al, 2009], HINT1 (protein kinase C interacting protein) [Barbier and Wang, 2009], ERK1 (extracellular signal regulated kinase 1) [Engel et al, 2009], and GRIK2 (metabotropic glutamate receptor 6) [Shaltiel et al, 2008;Malkesman et al, 2010]. Candidates emerging from genome-wide association studies of bipolar disorder (CACNA1C [Dao et al, 2010], ANK3 [Leussis et al, 2012]) were also validated in animal models.…”

Section: Animal Modelsmentioning

confidence: 99%

Convergent functional genomics of psychiatric disorders

Niculescu

2013

American J of Med Genetics Pt B

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Genetic and gene expression studies, in humans and animal models of psychiatric and other medical disorders, are becoming increasingly integrated. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit‐to‐disease way of extracting reproducible and biologically important signal, in contrast to the fit‐to‐cohort effect and limited reproducibility of human genetic analyses alone. With the advent of whole‐genome sequencing and the realization that a major portion of the non‐coding genome may contain regulatory variants, Convergent Functional Genomics (CFG) approaches are going to be essential to identify disease‐relevant signal from the tremendous polymorphic variation present in the general population. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer, cardiovascular diseases, and diabetes. © 2013 Wiley Periodicals, Inc.

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“…An analysis of these articles associated identified five genes as the most cited in the literature: CANAC1C [16][17][18][19][20][21][22][23][24] , DAOA [25][26][27][28][29][30][31][32] 22 . Some articles related the genetic polymorphism specifying the classification of TBI 8,25,27,32,35,36,39,41 , in addition to TBI and II 37 .…”

Section: Genes and Polymorphisms Associated With Demonstrationmentioning

confidence: 99%

Associação entre polimorfismos genéticos e transtorno bipolar

Alves¹,

Silva²,

Neto³

et al. 2012

Rev. psiquiatr. clín.

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Bipolar disorder (BD) is a common disorder that affects approximately 1% of the population. It is associated with both chronic and acute severe features, such as low remission rates and a high prevalence of clinical and psychiatric comorbidities. The aim of the present article is to synthesize data from various articles that investigated genetic polymorphisms associated with BD. The 129 articles selected identified 79 (85.87%) genes associated with BD. This analysis identified the five genes that are the most cited in the literature: CANAC1C, DAOA, TPH2, ANK3 and DISC1. Of the 92 genes identified in these articles, 33 (35.87%) showed no association with BD. This analysis showed that, despite recent advances with respect to the role of genetic polymorphism in predisposition to BD, further research is still required to elucidate its influence on this disorder.Alves VM, et al. / Rev Psiq Clín. 2012;39(1):34-9 Keywords: Bipolar disorder, genes, polymorphisms, heredity, gene ontology, association with bipolar disorder. ResumoTranstorno bipolar (TB) é uma doença comum que afeta aproximadamente 1% da população. Apresenta características crônicas e agudas graves, com índices de remissão de baixa e alta prevalência de comorbidades clínicas e psiquiátricas. O objetivo do presente artigo é sintetizar dados de vários artigos que investigaram polimorfismos genéticos associados com TB. Dentre os 129 artigos selecionados, identificaram-se 79 (85,87%) genes associados com TB. Essa análise identificou cinco genes que são os mais citados na literatura: CANAC1C, DAOA, TPH2, ANK3 e DISC1. Dos 92 genes identificados nesses artigos, 33 (35,87%) não mostraram associação com TB. Essa análise mostrou que, apesar dos avanços recentes com relação ao papel do polimorfismo genético na predisposição para TB, mais pesquisas ainda são necessárias para elucidar sua influência sobre esse transtorno.Alves VM, et al. / Rev Psiq Clín. 2012;39(1):34-9 Palavras-chave: Transtorno bipolar, genes, polimorfismos, hereditariedade, ontologia genética, associação com transtorno bipolar.

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Mood Disorder Susceptibility Gene CACNA1C Modifies Mood-Related Behaviors in Mice and Interacts with Sex to Influence Behavior in Mice and Diagnosis in Humans

Abstract: Background-Recent 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.

Cited by 165 publications

References 66 publications

Sex differences in animal models of psychiatric disorders

Sex differences in animal models of psychiatric disorders

Convergent functional genomics of psychiatric disorders

Associação entre polimorfismos genéticos e transtorno bipolar

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