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CACNA1C cognition

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https://www.readbyqxmd.com/read/28765577/cacna1c-polymorphisms-impact-cognitive-recovery-in-patients-with-bipolar-disorder-in-a-six-week-open-label-trial
#1
Kangguang Lin, Guiyun Xu, Lingling Shi, Weicong Lu, Lijie Guan, Huiyi Ouyang, Kun Chen, Yamei Dang, Libing Zhou, Kwok-Fai So
Cognitive impairments in bipolar patients deteriorate as the disorder progresses. Little is known about whether genetic risks impact cognitive recovery during the course from depression to remission. In this six-week open-label trial, we shed light on the impacts of six single nucleotide polymorphisms (SNPs) in the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene on cognitive recovery in 192 bipolar patients suffering a major depressive episode (MDE). The primary outcome measures were changes in a battery of neuropsychological tests following 6-week treatment...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28753255/comprehensive-analysis-of-two-shank3-and-the-cacna1c-mouse-models-of-autism-spectrum-disorder
#2
Patricia Kabitzke, Daniela Brunner, Dansha He, Pamela A Fazio, Kimberly Cox, Jane Sutphen, Lucinda Thiede, Emily Sabath, Taleen Hanania, Vadim Alexandrov, Randall Rasmusson, Will Spooren, Anirvan Ghosh, Pamela Feliciano, Barbara Biemans, Marta Benedetti, Alice Luo Clayton
To expand, analyze, and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng's Shank3(tm2Gfng) model, hereafter Shank3/F, Jiang's Shank3(tm1Yhj) model, hereafter Shank3/J, and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. The current study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11...
July 28, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28696432/cross-disorder-risk-gene-cacna1c-differentially-modulates-susceptibility-to-psychiatric-disorders-during-development-and-adulthood
#3
N Dedic, M L Pöhlmann, J S Richter, D Mehta, D Czamara, M W Metzger, J Dine, B T Bedenk, J Hartmann, K V Wagner, A Jurik, L M Almli, A Lori, S Moosmang, F Hofmann, C T Wotjak, G Rammes, M Eder, A Chen, K J Ressler, W Wurst, M V Schmidt, E B Binder, J M Deussing
Single-nucleotide polymorphisms (SNPs) in CACNA1C, the α1C subunit of the voltage-gated L-type calcium channel Cav1.2, rank among the most consistent and replicable genetics findings in psychiatry and have been associated with schizophrenia, bipolar disorder and major depression. However, genetic variants of complex diseases often only confer a marginal increase in disease risk, which is additionally influenced by the environment. Here we show that embryonic deletion of Cacna1c in forebrain glutamatergic neurons promotes the manifestation of endophenotypes related to psychiatric disorders including cognitive decline, impaired synaptic plasticity, reduced sociability, hyperactivity and increased anxiety...
July 11, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28607492/cognitive-characterization-of-schizophrenia-risk-variants-involved-in-synaptic-transmission-evidence-of-cacna1c-s-role-in-working-memory
#4
Donna Cosgrove, Omar Mothersill, Kimberley Kendall, Bettina Konte, Denise Harold, Ina Giegling, Annette Hartmann, Alex Richards, Kiran Mantripragada, Michael J Owen, Michael C O'Donovan, Michael Gill, Dan Rujescu, James Walters, Aiden Corvin, Derek W Morris, Gary Donohoe
With >100 common variants associated with schizophrenia risk, establishing their biological significance is a priority. We sought to establish cognitive effects of risk variants at loci implicated in synaptic transmission by (1) identifying GWAS schizophrenia variants whose associated gene function is related to synaptic transmission, and (2) testing for association between these and measures of neurocognitive function. We selected variants, reported in the largest GWAS to date, associated with genes involved in synaptic transmission...
December 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28604818/cacna1c-gene-regulates-behavioral-strategies-in-operant-rule-learning
#5
COMPARATIVE STUDY
Georgia Koppe, Anne Stephanie Mallien, Stefan Berger, Dusan Bartsch, Peter Gass, Barbara Vollmayr, Daniel Durstewitz
Behavioral experiments are usually designed to tap into a specific cognitive function, but animals may solve a given task through a variety of different and individual behavioral strategies, some of them not foreseen by the experimenter. Animal learning may therefore be seen more as the process of selecting among, and adapting, potential behavioral policies, rather than mere strengthening of associative links. Calcium influx through high-voltage-gated Ca2+ channels is central to synaptic plasticity, and altered expression of Cav1...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28593527/role-of-cacna1c-gene-polymorphisms-and-protein-expressions-in-the-pathogenesis-of-schizophrenia-a-case-control-study-in-a-chinese-population
#6
Sheng-Yu Zhang, Qiang Hu, Tao Tang, Chao Liu, Cheng-Chong Li, Xiao-Guang Yang, Yin-Yin Zang, Wei-Xiong Cai
The study aimed to investigate the correlations of CACNA1C genetic polymorphisms and protein expression with the pathogenesis of schizophrenia in a Chinese population. This research included 139 patients diagnosed with schizophrenia (case group) and 141 healthy volunteers (control group). Case and control samples were genotyped using denaturing high-performance liquid chromatography (DHPLC). Haplotypes of rs10848683, rs2238032, and rs2299661 were analyzed using the Shesis software. A mouse model of schizophrenia was established and assigned to test and blank groups...
August 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28584287/rescue-of-impaired-sociability-and-anxiety-like-behavior-in-adult-cacna1c-deficient-mice-by-pharmacologically-targeting-eif2%C3%AE
#7
Z D Kabir, A Che, D K Fischer, R C Rice, B K Rizzo, M Byrne, M J Glass, N V De Marco Garcia, A M Rajadhyaksha
CACNA1C, encoding the Cav1.2 subunit of L-type Ca(2+) channels, has emerged as one of the most prominent and highly replicable susceptibility genes for several neuropsychiatric disorders. Cav1.2 channels play a crucial role in calcium-mediated processes involved in brain development and neuronal function. Within the CACNA1C gene, disease-associated single-nucleotide polymorphisms have been associated with impaired social and cognitive processing and altered prefrontal cortical (PFC) structure and activity. These findings suggest that aberrant Cav1...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28497380/from-gene-to-behavior-l-type-calcium-channel-mechanisms-underlying-neuropsychiatric-symptoms
#8
REVIEW
Zeeba D Kabir, Arlene Martínez-Rivera, Anjali M Rajadhyaksha
The L-type calcium channels (LTCCs) Cav1.2 and Cav1.3, 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
https://www.readbyqxmd.com/read/28398341/the-cacna1c-risk-allele-rs1006737-is-associated-with-age-related-prefrontal-cortical-thinning-in-bipolar-i-disorder
#9
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
https://www.readbyqxmd.com/read/27683010/the-effects-of-a-genome-wide-supported-variant-in-the-cacna1c-gene-on-cortical-morphology-in-schizophrenia-patients-and-healthy-subjects
#10
Fanfan Zheng, Yue Cui, Hao Yan, Bing Liu, Tianzi Jiang
Schizophrenia is a highly heritable disorder with multiple susceptibility genes. Previously, we identified CACNA1C rs2007044 as a new risk locus for schizophrenia, with the minor allele G as risk allele. This association was recently validated by a powerful genome-wide association study. However, the underlying neural mechanisms remain unclear. Therefore, we tested whether the risk allele has an influence on cortical surface area and thickness in a sample of schizophrenia patients and healthy controls. We found significant genotype by diagnosis interactions on cortical surface area, but not thickness, in the right dorsolateral prefrontal cortex and the left superior parietal cortex, both of which are key components of the central executive network...
September 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27620326/association-of-cacna1c-and-syne1-in-offspring-of-patients-with-psychiatric-disorders
#11
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
https://www.readbyqxmd.com/read/27221213/polymorphisms-of-bdnf-and-cacna1c-are-not-associated-with-cognitive-functioning-in-bipolar-disorder-or-healthy-controls
#12
Sindre Rolstad, Carl Sellgren Majkowitz, Erik Joas, Carl Johan Ekman, Erik Pålsson, Mikael Landén
INTRODUCTION: The cause of cognitive dysfunction in bipolar disorder (BD) is not well understood. BDNF and CACNA1C are two susceptibility genes for the disorder that have also been reported to be associated with cognitive deficits in the disorder, but the studies have been small and with conflicting results. We therefore attempted to replicate an association between cognitive dysfunction with the most commonly studied single nucleotide polymorphisms rs6265 and rs1006737. METHODS: Regression models with five aggregated cognitive domains derived from a comprehensive test battery and IQ score were run using directly genotyped risk variants of SNPs rs6265 and rs1006737 as predictors with covariates as appropriate...
2016: Cognitive Neuropsychiatry
https://www.readbyqxmd.com/read/26913808/l-type-ca-2-channels-in-mood-cognition-and-addiction-integrating-human-and-rodent-studies-with-a-focus-on-behavioural-endophenotypes
#13
REVIEW
Z D Kabir, A S Lee, A M Rajadhyaksha
Brain Cav 1.2 and Cav 1.3 L-type Ca(2+) 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 Ca(2+) 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
https://www.readbyqxmd.com/read/26611642/cacna1c-risk-variant-affects-facial-emotion-recognition-in-healthy-individuals
#14
Vanessa Nieratschker, Christof Brückmann, Christian Plewnia
Recognition and correct interpretation of facial emotion is essential for social interaction and communication. Previous studies have shown that impairments in this cognitive domain are common features of several psychiatric disorders. Recent association studies identified CACNA1C as one of the most promising genetic risk factors for psychiatric disorders and previous evidence suggests that the most replicated risk variant in CACNA1C (rs1006737) is affecting emotion recognition and processing. However, studies investigating the influence of rs1006737 on this intermediate phenotype in healthy subjects at the behavioral level are largely missing to date...
2015: Scientific Reports
https://www.readbyqxmd.com/read/25989111/sex-dependent-modulation-of-age-related-cognitive-decline-by-the-l-type-calcium-channel-gene-cacna1c-cav-1-2
#15
Panos Zanos, Shambhu Bhat, Chantelle E Terrillion, Robert J Smith, Leonardo H Tonelli, Todd D Gould
Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively...
October 2015: European Journal of Neuroscience
https://www.readbyqxmd.com/read/25470093/cacna1c-genomewide-supported-psychosis-genetic-variation-affects-cortical-brain-white-matter-integrity-in-chinese-patients-with-schizophrenia
#16
Puay San Woon, Min Yi Sum, Carissa Nadia Kuswanto, Guo Liang Yang, Yih Yian Sitoh, Tuck Wah Soong, Tih Shih Lee, Wieslaw Lucjan Nowinski, Kang Sim
OBJECTIVE: Recent genomewide association studies have implicated the calcium channel, voltage-dependent, L type, alpha 1C subunit (CACNA1C) genetic variant in schizophrenia, which is associated with functional brain changes and cognitive deficits in healthy individuals. However, the impact of CACNA1C on brain white matter integrity in schizophrenia remains unclear. On the basis of prior evidence of CACNA1C-mediated changes involving cortical brain regions, we hypothesize that CACNA1C risk variant rs1006737 is associated with reductions of white matter integrity in the frontal, parietal, and temporal regions and cingulate gyrus...
November 2014: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/25290268/cacna1c-risk-variant-affects-reward-responsiveness-in-healthy-individuals
#17
T M Lancaster, E A Heerey, K Mantripragada, D E J Linden
The variant at rs1006737 in the L-type voltage-gated calcium channel (alpha 1c subunit) CACNA1C gene is reliably associated with both bipolar disorder and schizophrenia. We investigated whether this risk variant affects reward responsiveness because reward processing is one of the central cognitive-motivational domains implicated in both disorders. In a sample of 164 young, healthy individuals, we show a dose-dependent response, where the rs1006737 risk genotype was associated with blunted reward responsiveness, whereas discriminability did not significantly differ between genotype groups...
October 7, 2014: Translational Psychiatry
https://www.readbyqxmd.com/read/24996399/the-role-of-l-type-voltage-gated-calcium-channels-cav1-2-and-cav1-3-in-normal-and-pathological-brain-function
#18
REVIEW
Stefan M Berger, Dusan Bartsch
The use of specific activators and inhibitors that penetrate the central nervous system has suggested an essential functional role of L-type calcium channels (LTCC) in several important physiological processes of the brain, including the modulation of the mesoaccumbal dopamine signalling pathway, synaptic transmission of auditory stimuli and synaptic plasticity of neutral and aversive learning and memory processes. However, the lack of selectivity of available pharmacological agents towards the most prominent LTCC isoforms in the brain, namely Cav1...
August 2014: Cell and Tissue Research
https://www.readbyqxmd.com/read/24944871/candidate-gene-associations-with-mood-disorder-cognitive-vulnerability-and-fronto-limbic-volumes
#19
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
https://www.readbyqxmd.com/read/24773605/exome-sequencing-helped-the-fine-diagnosis-of-two-siblings-afflicted-with-atypical-timothy-syndrome-ts2
#20
Sebastian Fröhler, Moritz Kieslich, Claudia Langnick, Mirjam Feldkamp, Bernd Opgen-Rhein, Felix Berger, Joachim C Will, Wei Chen
BACKGROUND: Long-QT syndrome (LQTS) causes a prolongation of the QT-interval in the ECG leading to life threatening tachyarrhythmia and ventricular fibrillation. One atypical form of LQTS, Timothy syndrome (TS), is associated with syndactyly, immune deficiency, cognitive and neurological abnormalities as well as distinct cranio-facial abnormalities. CASE PRESENTATION: On a family with both children diagnosed with clinical LQTS, we performed whole exome sequencing to comprehensively screen for causative mutations after a targeted candidate gene panel screen for Long-QT syndrome target genes failed to identify any underlying genetic defect...
2014: BMC Medical Genetics
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