The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder

Soeiro-de-Souza, Márcio G.; Lafer, Beny; Moreno, Ricardo Alberto; Nery, Fabiano G.; Chile, Thais; Chaim, K.; Leite, Cláudia da Costa; Machado‐Vieira, Rodrigo; Otaduy, Maria Concepción García; Vallada, Homero

doi:10.1038/tp.2017.57

Cited by 46 publications

(20 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…According to our analysis, the right prefrontal cortical thickness of our patients was related to mood stabilizers and was not significantly associated with the presence of the CACNA1C risk A allele rs1006737. These results are discordant to previous works, where the presence of this risk allele relates to increased GM density and cortical thickness 12,18,37 even in healthy subjects. 13 There are two characteristics of our study that might explain this discrepancy.…”

Section: Discussioncontrasting

confidence: 77%

“…12,17 A recent analysis of 117 BD Brazilian patients associated the risk A allele with greater cortical thickness measures in PFC. 18 However, these studies used heterogenic samples that included patients treated with different medications which are a known cause of brain morphometric changes. 9 Among the treatments for BD, mood stabilizers are medications with antimanic, antidepressant and prophylactic properties.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CACNA1C Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder

Rodríguez-Ramírez¹,

Meza-Urzúa²,

Cedillo-Ríos³

et al. 2020

NDT

View full text Add to dashboard Cite

Purpose: Bipolar disorder (BD) is a condition associated with structural alterations in the prefrontal cortex (PFC); some genetic variants and mood stabilizer medications like lithium or valproate are associated with these changes. CACNA1C is a gene involved in BD pathology and brain function; carriers of the A allele of rs1006737 are reported to have increased risk for BD and increased cortical thickness (CT) in the PFC compared to noncarriers. Lithium is also associated with increased CT in the PFC of BD subjects compared to the ones on valproate. The influence of these treatments and gene variants over the PFC structure of Mexican subjects has not been explored. Therefore, we evaluate the effects of mood stabilizers and risk A allele of CACNA1C rs1006737 on the prefrontal cortical thickness of Mexican BD patients treated with lithium or valproate. Patients and Methods: A cross-sectional study of 40 BD type I euthymic adult outpatients (20 treated with lithium and 20 with valproate) who underwent a 3T T1-weighted 3D brain scan and genotyping for CACNA1C risk allele rs1006737 was conducted. We performed a cortical thickness analysis of the dorsolateral and orbitofrontal regions of the prefrontal cortex with BrainVoyager 20.6. The effects of treatment and gene variants were analyzed with a two-way multivariate analysis of covariance. Results: There was no association of CACNA1C risk allele rs1006737 with CT measures of both PFCs nor significant interaction between the genetic variant and treatment. Mood stabilizers reported the main effect on the CT measures of the right PFC of our sample. Patients on treatment with lithium showed higher mean CT on the right orbitofrontal cortex. Conclusion: We did not find any association between the prefrontal CT and CACNA1C risk A allele rs1006737 in BD Mexican patients treated with lithium or valproate. Our results suggest that mood stabilizers had the main effect in the CT of the right PFC.

show abstract

Section: Discussioncontrasting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

CACNA1C Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder

Rodríguez-Ramírez¹,

Meza-Urzúa²,

Cedillo-Ríos³

et al. 2020

NDT

View full text Add to dashboard Cite

show abstract

“…Ca v 1.2 channels are widely expressed in dendrites and spines, where they regulate calcium entry 118 . Brain imaging studies have found that the CACNA1C risk allele is associated with an age-related prefrontal cortical thinning in individuals with bipolar disorder 119 . Activity-dependent pruning of the excitatory synapses of medium spiny neurons is dependent on Ca 2+ entry through Ca v 1.2 in co-culture models, indicating that pruning may play a part in this age-related thinning 120 .…”

Section: Genetic Risk and Structural Plasticitymentioning

confidence: 99%

Dendritic structural plasticity and neuropsychiatric disease

2018

View full text Add to dashboard Cite

The structure of neuronal circuits that subserve cognitive functions in the brain is shaped and refined throughout development and into adulthood. Evidence from human and animal studies suggests that the cellular and synaptic substrates of these circuits are atypical in neuropsychiatric disorders, indicating that altered structural plasticity may be an important part of the disease biology. Advances in genetics have redefined our understanding of neuropsychiatric disorders and have revealed a spectrum of risk factors that impact pathways known to influence structural plasticity. In this Review, we discuss the importance of recent genetic findings on the different mechanisms of structural plasticity and propose that these converge on shared pathways that can be targeted with novel therapeutics.

show abstract

“…These intermediate phenotypes are assumed to involve the same biological pathways as the illness but to relate more closely to the effects of relevant genes [61-65]. Recent studies of several psychiatric candidate genes including ZNF804A [66-68] and CACNA1C [69-72] have already demonstrated the validity and reliability of this approach. We previously also analyzed the association between VRK2 SNPs and brain phenotypes related to psychiatric disorders [34] and found that the psychiatric risk allele [C] in rs2312147 was associated with reduced total brain volume and white matter volume in healthy individuals, which was in line with clinical characteristics in the brains of psychiatric patients compared with healthy controls [73].…”

Section: Identification Of Vrk2 Variants In Psychiatric Disorders Amomentioning

confidence: 99%

VRK2, a Candidate Gene for Psychiatric and Neurological Disorders

Yue

2018

Complex Psychiatry

View full text Add to dashboard Cite

Recent large-scale genetic approaches, such as genome-wide association studies, have identified multiple genetic variations that contribute to the risk of mental illnesses, among which single nucleotide polymorphisms (SNPs) within or near the vaccinia related kinase 2 (VRK2) gene have gained consistent support for their correlations with multiple psychiatric and neurological disorders including schizophrenia (SCZ), major depressive disorder (MDD), and genetic generalized epilepsy. For instance, the genetic variant rs1518395 in VRK2 showed genome-wide significant associations with SCZ (35,476 cases and 46,839 controls, p = 3.43 × 10^–8) and MDD (130,620 cases and 347,620 controls, p = 4.32 × 10^–12) in European populations. This SNP was also genome-wide significantly associated with SCZ in Han Chinese population (12,083 cases and 24,097 controls, p = 3.78 × 10^–13), and all associations were in the same direction of allelic effects. These studies highlight the potential roles of VRK2 in the central nervous system, and this gene therefore might be a good candidate to investigate the shared genetic and molecular basis between SCZ and MDD, as it is one of the few genes known to show genome-wide significant associations with both illnesses. Furthermore, the VRK2 gene was found to be involved in multiple other congenital deficits related to the malfunction of neurodevelopment, adding further support for the involvement of this gene in the pathogenesis of these neurological and psychiatric illnesses. While the precise function of VRK2 in these conditions remains unclear, preliminary evidence suggests that it may affect neuronal proliferation and migration via interacting with multiple essential signaling pathways involving other susceptibility genes/proteins for psychiatric disorders. Here, we have reviewed the recent progress of genetic and molecular studies of VRK2, with an emphasis on its role in psychiatric illnesses and neurological functions. We believe that attention to this important gene is necessary, and further investigations of VRK2 may provide hints into the underlying mechanisms of SCZ and MDD.

show abstract

The CACNA1C risk allele rs1006737 is associated with age-related prefrontal cortical thinning in bipolar I disorder

Cited by 46 publications

References 78 publications

<p><em>CACNA1C</em> Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder</p>

<p><em>CACNA1C</em> Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder</p>

Dendritic structural plasticity and neuropsychiatric disease

<b><i>VRK2</i></b>, a Candidate Gene for Psychiatric and Neurological Disorders

Contact Info

Product

Resources

About