cerebellum and cacna1c

OBJECTIVES: This study aimed to examine whether the CACNA1C gene rs11832738 polymorphism and major depressive disorder (MDD) have an interactive effect on the untreated regional amplitude of low-frequency fluctuation (ALFF) and to determine whether regional ALFF mediates the association between CACNA1C rs11832738 and MDD. METHODS: A total of 116 patients with MDD and 66 normal controls (NCs) were recruited. The MDD and NC groups were further divided into two groups according to genotype: carriers of the G allele (G-carrier group, GG/GA genotypes; MDD, n = 61; NC, n = 26) and AA homozygous group (MDD, n = 55; NC, n = 40)...

RNA splicing is a key mechanism linking genetic variation with psychiatric disorders. Splicing profiles are particularly diverse in brain and difficult to accurately identify and quantify. We developed a new approach to address this challenge, combining long-range PCR and nanopore sequencing with a novel bioinformatics pipeline. We identify the full-length coding transcripts of CACNA1C in human brain. CACNA1C is a psychiatric risk gene that encodes the voltage-gated calcium channel CaV 1.2. We show that CACNA1C's transcript profile is substantially more complex than appreciated, identifying 38 novel exons and 241 novel transcripts...

The progress of schizophrenia at various stages is an intriguing question, which has been explored to some degree using single-modality brain imaging data, e.g. gray matter (GM) or functional connectivity (FC). However it remains unclear how those changes from different modalities are correlated with each other and if the sensitivity to duration of illness and disease stages across modalities is different. In this work, we jointly analyzed FC, GM volume and single nucleotide polymorphisms (SNPs) data of 159 individuals including healthy controls (HC), drug-naïve first-episode schizophrenia (FESZ) and chronic schizophrenia patients (CSZ), aiming to evaluate the links among SNP, FC and GM patterns, and their sensitivity to duration of illness and disease stages in schizophrenia...

Schizophrenia (SZ) is a highly heritable disease exhibiting substantial structural and functional brain impairments. The duration of illness and medication use may cause different presentations of impairments in patients. To understand the progressive variations of the disease, most recent studies have reported brain functional or structural abnormalities associated with illness duration, but a comprehensive study of pathology underlying brain structure, function and illness duration is still limited. In this work, we employed a three-way parallel independent component analysis (pICA) algorithm to jointly analyze grey matter volume(GM), functional connectivity (FC) and single nucleotide polymorphisms (SNPs) from drug-naïve first-episode [FESZ], chronic schizophrenia [CSZ]) and healthy controls[HC], aiming to identify the linked alterations in SNP-GM-FC components, and evaluate the impairment speed of imaging measures associated with SZ-susceptible genetic variants in different disease stages (FESZ and CSZ)...

CACNA1C-rs1006737 and ZNF804A-rs1344706 polymorphisms are among the most robustly associated with schizophrenia (SCZ) and bipolar disorder (BD), and recently with brain phenotypes. As these patients show abnormal verbal fluency (VF) and related brain activation, we asked whether the latter was affected by these polymorphisms (alone and in interaction)-to better understand how they might induce risk. We recently reported effects on functional VF-related (for ZNF804A-rs1344706) and structural (for both) connectivity...

Genetic studies found the A allele of the single nucleotide polymorphism rs1006737 in the CACNA1C gene, which encodes for the alpha 1C subunit of the voltage-dependent, L-type calcium ion channel Cav1.2, to be overrepresented in patients with major depressive disorder (MDD). Altered prefrontal brain functioning and impaired semantic verbal fluency (SVF) are robust findings in these patients. A recent functional magnetic resonance imaging (fMRI) study found the A allele to be associated with poorer performance and increased left inferior frontal gyrus (IFG) activation during SVF tasks in healthy subjects...

Timothy Syndrome (TS) is caused by very rare exonic mutations of the CACNA1C gene that produce delayed inactivation of Cav1.2 voltage-gated calcium channels during cellular action potentials, with greatly increased influx of calcium into the activated cells. The major clinical feature of this syndrome is a long QT interval that results in cardiac arrhythmias. However, TS also includes cognitive impairment, autism and major developmental delays in many of the patients. We observed the appearance of bipolar disorder (BD) in a patient with a previously reported case of TS, who is one of the very few patients to survive childhood...