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CACNA1C mood

Zeeba D Kabir, Arlene Martínez-Rivera, Anjali M Rajadhyaksha
The L-type calcium channels (LTCCs) Cav 1.2 and Cav 1.3, encoded by the CACNA1C and CACNA1D genes, respectively, are important regulators of calcium influx into cells and are critical for normal brain development and plasticity. In humans, CACNA1C has emerged as one of the most widely reproduced and prominent candidate risk genes for a range of neuropsychiatric disorders, including bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder...
July 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
M G Soeiro-de-Souza, B Lafer, R A Moreno, F G Nery, T Chile, K Chaim, C da Costa Leite, R Machado-Vieira, M C G Otaduy, H Vallada
Calcium channels control the inflow of calcium ions into cells and are involved in diverse cellular functions. The CACNA1C gene polymorphism rs1006737 A allele has been strongly associated with increased risk for bipolar disorder (BD) and with modulation of brain morphology. The medial prefrontal cortex (mPFC) has been widely associated with mood regulation in BD, but the role of this CACNA1C polymorphism in mPFC morphology and brain aging has yet to be elucidated. One hundred seventeen euthymic BD type I subjects were genotyped for CACNA1C rs1006737 and underwent 3 T three-dimensional structural magnetic resonance imaging scans to determine cortical thickness of mPFC components (superior frontal cortex (sFC), medial orbitofrontal cortex (mOFC), caudal anterior cingulate cortex (cACC) and rostral anterior cingulate cortex (rACC))...
April 11, 2017: Translational Psychiatry
Patricia Gassó, Vanessa Sánchez-Gistau, Sergi Mas, Gisela Sugranyes, Natalia Rodríguez, Daniel Boloc, Elena de la Serna, Soledad Romero, Dolores Moreno, Carmen Moreno, Covadonga M Díaz-Caneja, Amalia Lafuente, Josefina Castro-Fornieles
Schizophrenia (SZ) and bipolar disorder (BD) are severe mental diseases associated with cognitive impairment, mood disturbance, and psychosis. Both disorders are highly heritable and share a common genetic background. The present study assesses, for the first time, differences in genotype frequencies of polymorphisms located in genes involved in neurodevelopment and synaptic plasticity between genetic high-risk individuals (offspring of patients with SZ or BD; N=100: 31 and 69, respectively) and control subjects (offspring of community controls; N=96)...
November 30, 2016: Psychiatry Research
Z D Kabir, A S Lee, A M Rajadhyaksha
Brain Cav 1.2 and Cav 1.3 L-type Ca2+ channels play key physiological roles in various neuronal processes that contribute to brain function. Genetic studies have recently identified CACNA1C as a candidate risk gene for bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder (MDD) and autism spectrum disorder (ASD), and CACNA1D for BD and ASD, suggesting a contribution of Cav 1.2 and Cav 1.3 Ca2+ signalling to the pathophysiology of neuropsychiatric disorders. Once considered sole clinical entities, it is now clear that BD, SCZ, MDD and ASD share common phenotypic features, most likely due to overlapping neurocircuitry and common molecular mechanisms...
October 15, 2016: Journal of Physiology
Michael J McCarthy, Melissa J Le Roux, Heather Wei, Stephen Beesley, John R Kelsoe, David K Welsh
UNLABELLED: Bipolar disorder (BD) is associated with mood episodes and low amplitude circadian rhythms. Previously, we demonstrated that fibroblasts grown from BD patients show weaker amplification of circadian rhythms by lithium compared to control cells. Since calcium signals impact upon the circadian clock, and L-type calcium channels (LTCC) have emerged as genetic risk factors for BD, we examined whether loss of function in LTCCs accounts for the attenuated response to lithium in BD cells...
February 2016: Neuropharmacology
E Pasparakis, E Koiliari, C Zouraraki, E-M Tsapakis, P Roussos, S G Giakoumaki, P Bitsios
BACKGROUND: The CACNA1C rs1006737 risk A allele has been associated with affective psychoses and functional studies indicate that it is associated with increased hippocampal/amygdala activity during emotional face-processing. Here we studied the impact of the risk A allele on affective startle modulation. METHODS: Hundred and ninety-four healthy males stratified for their CACNA1C rs1006737 genotype (GG:111, GA:67, AA:16) were presented with 18 pleasant, 18 unpleasant and 18 neutral pictures with acoustic probes (104 dB) occurring during 12 pictures in each affective category...
June 2015: European Psychiatry: the Journal of the Association of European Psychiatrists
Thomas W Frazier, Eric A Youngstrom, Brian A Frankel, Giovana B Zunta-Soares, Marsal Sanches, Michael Escamilla, David A Nielsen, Jair C Soares
BACKGROUND: Four of the most consistently replicated variants associated with mood disorder occur in genes important for synaptic function: ANK3 (rs10994336), BDNF (rs6265), CACNA1C (rs1006737), and DGKH (rs1170191). AIMS: The present study examined associations between these candidates, mood disorder diagnoses, cognition, and fronto-limbic regions implicated in affect regulation. METHODS AND MATERIALS: Participants included 128 individuals with bipolar disorder (33% male, Mean age = 38...
May 2014: Brain and Behavior
B H Schott, A Assmann, P Schmierer, J Soch, S Erk, M Garbusow, S Mohnke, L Pöhland, N Romanczuk-Seiferth, A Barman, T Wüstenberg, L Haddad, O Grimm, S Witt, S Richter, M Klein, H Schütze, T W Mühleisen, S Cichon, M Rietschel, M M Noethen, H Tost, E D Gundelfinger, E Düzel, A Heinz, A Meyer-Lindenberg, C I Seidenbecher, H Walter
Recent genome-wide association studies have pointed to single-nucleotide polymorphisms (SNPs) in genes encoding the neuronal calcium channel CaV1.2 (CACNA1C; rs1006737) and the presynaptic active zone protein Piccolo (PCLO; rs2522833) as risk factors for affective disorders, particularly major depression. Previous neuroimaging studies of depression-related endophenotypes have highlighted the role of the subgenual cingulate cortex (CG25) in negative mood and depressive psychopathology. Here, we aimed to assess how recently associated PCLO and CACNA1C depression risk alleles jointly affect memory-related CG25 activity as an intermediate phenotype in clinically healthy humans...
March 18, 2014: Translational Psychiatry
Claudia Wolf, Holger Mohr, Thomas Schneider-Axmann, Andreas Reif, Thomas Wobrock, Harald Scherk, Susanne Kraft, Andrea Schmitt, Peter Falkai, Oliver Gruber
Affective deficits are one common denominator of schizophrenia (SZ), bipolar disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated as one of the major structures involved in emotion regulation. Previous findings of differences in amygdala volume between healthy controls and patients with SZ, BD or OCD diverge with respect to the affected hemisphere, size and direction of the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as structural and functional variation in the amygdala in healthy people and patients with BD...
March 2014: European Archives of Psychiatry and Clinical Neuroscience
Xu Zhang, Chen Zhang, Zhiguo Wu, Zuowei Wang, Daihui Peng, Jun Chen, Wu Hong, Chengmei Yuan, Zezhi Li, Shunying Yu, Yiru Fang
BACKGROUND: A growing body of evidence highlights the existence of shared genetic susceptibility to both major depressive disorder (MDD) and bipolar disorder (BD), suggesting some potential genetic overlap between the disorders. Genome-wide association studies have identified consistent association of single nucleotide polymorphisms of the α-1 C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with MDD and BD, suggesting CACNA1C as a promising candidate gene for susceptibility to mood disorders...
September 5, 2013: Journal of Affective Disorders
M Li, X-J Luo, M Rietschel, C M Lewis, M Mattheisen, B Müller-Myhsok, S Jamain, M Leboyer, M Landén, P M Thompson, S Cichon, M M Nöthen, T G Schulze, P F Sullivan, S E Bergen, G Donohoe, D W Morris, A Hargreaves, M Gill, A Corvin, C Hultman, A W Toga, L Shi, Q Lin, H Shi, L Gan, A Meyer-Lindenberg, D Czamara, C Henry, B Etain, J C Bis, M A Ikram, M Fornage, S Debette, L J Launer, S Seshadri, S Erk, H Walter, A Heinz, F Bellivier, J L Stein, S E Medland, A Arias Vasquez, D P Hibar, B Franke, N G Martin, M J Wright, B Su
Bipolar disorder (BD) is a polygenic disorder that shares substantial genetic risk factors with major depressive disorder (MDD). Genetic analyses have reported numerous BD susceptibility genes, while some variants, such as single-nucleotide polymorphisms (SNPs) in CACNA1C have been successfully replicated, many others have not and subsequently their effects on the intermediate phenotypes cannot be verified. Here, we studied the MDD-related gene CREB1 in a set of independent BD sample groups of European ancestry (a total of 64,888 subjects) and identified multiple SNPs significantly associated with BD (the most significant being SNP rs6785[A], P=6...
April 2014: Molecular Psychiatry
M G Soeiro-de-Souza, D S Bio, V V Dias, E Vieta, R Machado-Vieira, R A Moreno
OBJECTIVE: Calcium channels are important for converting electrical activity into biochemical events. A single nucleotide polymorphism (SNP) (rs1006737) in the CACNA1C gene has been strongly associated with increased risk for Bipolar disorder (BD) in genome-wide association studies. Recently, this same SNP has been reported to influence executive function in schizophrenia and controls, but it remains unclear whether this SNP affects behaviour, especially cognition in subjects with BD...
November 2013: Acta Psychiatrica Scandinavica
Hiroaki Hori, Noriko Yamamoto, Takashi Fujii, Toshiya Teraishi, Daimei Sasayama, Junko Matsuo, Yumiko Kawamoto, Yukiko Kinoshita, Miho Ota, Kotaro Hattori, Masahiko Tatsumi, Kunimasa Arima, Hiroshi Kunugi
Recent genetic association studies have identified the A-allele of rs1006737 within CACNA1C as a risk factor for schizophrenia as well as mood disorders. Some evidence suggests that this polymorphism plays a role in cognitive function both in schizophrenia patients and healthy individuals; however, the precise nature of this association remains unclear. Here we investigated the possible association of this polymorphism with a wide range of neurocognitive functions in schizophrenia patients and in healthy subjects...
2012: Scientific Reports
Shambhu Bhat, David T Dao, Chantelle E Terrillion, Michal Arad, Robert J Smith, Nikolai M Soldatov, Todd D Gould
One of the most consistent genetic findings to have emerged from bipolar disorder genome wide association studies (GWAS) is with CACNA1C, a gene that codes for the α(1C) subunit of the Ca(v)1.2 voltage-dependent L-type calcium channel (LTCC). Genetic variation in CACNA1C have also been associated with depression, schizophrenia, autism spectrum disorders, as well as changes in brain function and structure in control subjects who have no diagnosable psychiatric illness. These data are consistent with a continuum of shared neurobiological vulnerability between diverse-Diagnostic and Statistical Manual (DSM) defined-neuropsychiatric diseases...
October 2012: Progress in Neurobiology
Márcio Gerhardt Soeiro-de-Souza, Maria Concepción Garcia Otaduy, Carolina Zadres Dias, Danielle S Bio, Rodrigo Machado-Vieira, Ricardo Alberto Moreno
INTRODUCTION: Impairments in facial emotion recognition (FER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the α1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function...
December 1, 2012: Journal of Affective Disorders
Panos Roussos, Stella G Giakoumaki, Anastasios Georgakopoulos, Nikolaos K Robakis, Panos Bitsios
OBJECTIVES: The rs10994336 ANK3 and rs1006737 CACNA1C genetic variants have recently been identified as the most consistent, genome-wide significant risk factors for bipolar disorder, while the CACNA1C variant has also been associated with schizophrenia and major depression. The aim of this study was to examine the phenotypic consequences of the risk CACNA1C and ANK3 alleles in a large homogeneous cohort of healthy young males. METHODS: We recruited 703 randomly selected, healthy army conscripts (mean age 22...
May 2011: Bipolar Disorders
Heike Weber, Sarah Kittel-Schneider, Alexandra Gessner, Katharina Domschke, Maria Neuner, Christian P Jacob, Henriette N Buttenschon, Andrea Boreatti-Hümmer, Julia Volkert, Sabine Herterich, Bernhard T Baune, Silke Gross-Lesch, Juliane Kopf, Susanne Kreiker, Thuy Trang Nguyen, Lena Weissflog, Volker Arolt, Ole Mors, Jürgen Deckert, Klaus-Peter Lesch, Andreas Reif
Recently, several genome-wide association studies (GWAS) on bipolar disorder (BPD) suggested novel risk genes. However, only few of them were followed up and further, the specificity of these genes is even more elusive. To address these issues, we genotyped SNPs in ANK3, CACNA1C, CMTM8, DGKH, EGFR, and NPAS3, which were significantly associated with BPD in previous GWAS, in a sample of 380 BPD patients. Replicated SNPs were then followed up in patients suffering from unipolar depression (UPD; n=387) or adult attention-deficit/hyperactivity disorder (aADHD; n=535)...
September 2011: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
S D Detera-Wadleigh, N Akula
Meta analysis of association data of mood disorders has shown evidence for the role of particular genes in genetic risk. Integration of association data from meta analysis with differential expression data in brains of mood disorder patients could heighten the level of support for specific genes. To identify molecular mechanisms that may be disrupted in disease, a systems approach that involves analysis of biological networks created by these selected genes was employed.Interaction networks of hierarchical groupings of selected genes were generated using the Michigan Molecular Interactions (MiMI) software...
May 2011: Pharmacopsychiatry
E T Landaas, S Johansson, A Halmøy, K J Oedegaard, O B Fasmer, J Haavik
Attention-deficit/hyperactivity disorder (ADHD) has an estimated prevalence of 3-5% in adults. Genome-wide association (GWA) studies have not been performed in adults with ADHD and studies in children have so far been inconclusive, possibly because of the small sample sizes. Larger GWA studies have been performed on bipolar disorder (BD) and BD symptoms, and several potential risk genes have been reported. ADHD and BD share many clinical features and comorbidity between these two disorders is common. We therefore wanted to examine whether the reported BD genetic variants in CACNA1C, ANK3, MYO5B, TSPAN8 and ZNF804A loci are associated with ADHD or with scores on the Mood Disorder Questionnaire (MDQ), a commonly used screening instrument for bipolar spectrum disorders...
June 2011: Genes, Brain, and Behavior
Francesco Casamassima, Aleena C Hay, Alessandra Benedetti, Lorenzo Lattanzi, Giovanni B Cassano, Roy H Perlis
Emerging evidence from genome-wide association studies (GWAS) support the association of polymorphisms in the alpha 1C subunit of the L-type voltage-gated calcium channel gene (CACNA1C) with bipolar disorder. These studies extend a rich prior literature implicating dysfunction of L-type calcium channels (LTCCs) in the pathophysiology of neuropsychiatric disorders. Moreover, calcium channel blockers reduce Ca(2+) flux by binding to the α1 subunit of the LTCC and are used extensively for treating hypertension, preventing angina, cardiac arrhythmias and stroke...
December 5, 2010: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
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