PCLO gene: Its role in vulnerability to major depressive disorder

Minelli, Alessandra; Scassellati, Catia; Cloninger, C. Robert; Tessari, Elisabetta; Bortolomasi, Marco; Bonvicini, Cristian; Giacopuzzi, M.; Frisoni, Giovanni B.; Gennarelli, Massimo

doi:10.1016/j.jad.2012.01.028

Cited by 22 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Weidenhofer et al reported an increase in the gene expression of PCLO , Rims2 , and Rims3 in the amygdala in SCZ [37], although some variability in Piccolo expression was observed, suggesting that this protein might not be affected in some cases of schizophrenia. A GWA study conducted in the Netherlands [40] and corroborated by others [41, 42] found an association of the PCLO gene with MDD due to a single nucleotide polymorphism (SNP), SNP rs2522833, in which a serine is replaced with alanine in the C2A domain, a region known to bind phosphatidylinositol or synaptotagmin-1. Following this finding, Furukawa-Hibi et al [85] produced a transgenic mouse overexpressing the Piccolo C2A domain.…”

Section: Presynaptic Proteinsmentioning

confidence: 88%

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

2017

View full text Add to dashboard Cite

Synapses are complex structures that allow communication between neurons in the central nervous system. Studies conducted in vertebrate and invertebrate models have contributed to the knowledge of the function of synaptic proteins. The functional synapse requires numerous protein complexes with specialized functions that are regulated in space and time to allow synaptic plasticity. However, their interplay during neuronal development, learning, and memory is poorly understood. Accumulating evidence links synapse proteins to neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. In this review, we describe the way in which several proteins that participate in cell adhesion, scaffolding, exocytosis, and neurotransmitter reception from presynaptic and postsynaptic compartments, mainly from excitatory synapses, have been associated with several synaptopathies, and we relate their functions to the disease phenotype.

show abstract

Section: Presynaptic Proteinsmentioning

confidence: 88%

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

2017

View full text Add to dashboard Cite

show abstract

“…A larger series of replication samples did not support this association but an exploratory analysis of the subset of samples most similar to the discovery sample yielded nearly significant association for a non-synonymous PCLO SNP (rs2522833). Although subsequent candidate gene studies have implicated this or other PCLO SNPs in depression (Hek et al, 2010;Minelli et al, 2012), bipolar disorder (Choi et al, 2011), and HPA axis function (Kuehner et al, 2011;Schuhmacher et al, 2011), the gene has not shown association in independent GWAS of MDD. A subsequent GWAS (Kohli et al, 2011) reported a significant recessive association for an SNP (rs1545843) in SLC6A15, a gene involved in transporting neutral amino acids.…”

Section: Common Genetic Variationmentioning

confidence: 97%

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Smoller

2015

Neuropsychopharmacol

349

243

View full text Add to dashboard Cite

Research into the causes of psychopathology has largely focused on two broad etiologic factors: genetic vulnerability and environmental stressors. An important role for familial/heritable factors in the etiology of a broad range of psychiatric disorders was established well before the modern era of genomic research. This review focuses on the genetic basis of three disorder categories-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and the anxiety disorders-for which environmental stressors and stress responses are understood to be central to pathogenesis. Each of these disorders aggregates in families and is moderately heritable. More recently, molecular genetic approaches, including genome-wide studies of genetic variation, have been applied to identify specific risk variants. In this review, I summarize evidence for genetic contributions to PTSD, MDD, and the anxiety disorders including genetic epidemiology, the role of common genetic variation, the role of rare and structural variation, and the role of gene-environment interaction. Available data suggest that stress-related disorders are highly complex and polygenic and, despite substantial progress in other areas of psychiatric genetics, few risk loci have been identified for these disorders. Progress in this area will likely require analysis of much larger sample sizes than have been reported to date. The phenotypic complexity and genetic overlap among these disorders present further challenges. The review concludes with a discussion of prospects for clinical translation of genetic findings and future directions for research.

show abstract

“…The association with MDD was independently reproduced by others (Hek et al, 2010;Aragam et al, 2011;Woudstra et al, 2012Woudstra et al, , 2013Verbeek et al, 2013), although it was not replicated in the more recent and largest GWAS to date (Ripke et al, 2013). A recent replicate case-control study (Minelli et al, 2012) investigated depression-related personality traits in healthy subjects as a function of the PCLO rs2522833 genotype. This study showed that rs2522833 homozygotes were more frequent among MDD patients than in controls (p < 0.01).…”

Section: Introductionmentioning

confidence: 99%

Functional characterization of the PCLO p.Ser4814Ala variant associated with major depressive disorder reveals cellular but not behavioral differences

et al. 2015

View full text Add to dashboard Cite

PCLO gene: Its role in vulnerability to major depressive disorder

Cited by 22 publications

References 34 publications

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

Emerging Synaptic Molecules as Candidates in the Etiology of Neurological Disorders

The Genetics of Stress-Related Disorders: PTSD, Depression, and Anxiety Disorders

Functional characterization of the PCLO p.Ser4814Ala variant associated with major depressive disorder reveals cellular but not behavioral differences

Contact Info

Product

Resources

About