Can depression be genetic yahoo dating

Are depression and anxiety genetic? | Yahoo Answers

can depression be genetic yahoo dating

Up to date I'm still living happily with my girlfriend. Depression can have a genetic component, but it does not mean that your children will. The thing about depression is that, if you're up and about enough to date, and but there is also the genetic and chemical component, that's why it can run in. E-mail: [email protected] Received date: July 20, ; Accepted date: August 08, ; Published Parkinson disease; Genetic; Lewy bodies disease; Gene's mutations An Icelandic study raised the possibility that PD can have a familial () Mitochondria and energetic depression in cell pathophysiology.

The mutation GS of LRRK2 is carried by the same haplotype in all patients suggesting the existence of a unique founder effect [ ]. Up-regulation of kinase activity of LRRK2 caused by GS and IT mutations is at the origin of gain-of-function with deleterious role on the viability of dopaminergic neurons [ ].

LRRK2 is involved in endosomal-autophagic pathway, accumulation of autophagic vacuoles in response to autophagic stress representing a biochemical event of PD pathogenesis [ ]. A LRRK2 neuroprotector role mediated by the regulation of mitogen activating protein kinase pathway which functional core is the LRRK2 kinase domain has also been proposed [ ].

The pathological up regulation of kinase activity by LRRK2 mutations is associated with significantly higher apoptotic cell death [ ]. LRRK2 represents one of the components of Lewy bodies found in the substantia nigra in a quarter of idiopathic PD patients and even in a half of LBs in a patient with GS mutation [ ]. LRRK2 mutations induce neuritis length and branching reduction supporting the role of LRRK2 in regulation of neuritis process morphology [ ].

Another pathogenic mechanism involve the dopamine transmission and D2 dysfunction causes by RC mutation [ ].

Can depression be genetic yahoo dating site

Clinical features comprised a very early onset of the disease with rigid-akinetic phenotype, less rest tremor, pyramidal syndrome, progressive cognitive impairment, vertical gaze palsy, mini myoclonus, insomnia and good response to levodopa [ ]. Mutations of this gene which maps on chromosome 1p36 cause PD in a rare form known as Kufor- Rakeb syndrome [ ]. Compound heterozygous mutations were reported in the affected members of a Chilean family with lower splicing efficiency of exon 13 [ ].

Homozygous missense mutation GlyArg was identified in one sporadic case from Brazil with juvenile Parkinsonism [ ]. Brain iron accumulation in the striatal region as a histopathological marker of Kufor-Rakeb syndrome provides support to its membership to the group of syndromes of neurodegeneration with brain iron accumulation NBIA [ ].

ATP13A2 is a predicted lysosomal P-type transmembrane cation transporting ATPase, whereas mutant forms are transformed in the endoplasmic reticulum and have been functionally linked with neurodegeneration phenotype [ ]. PARK10 A genome-wide scan in patients of 51 Icelandic families has been identified a novel locus on the chromosome 1p32 concerning late onset PD patients [ ].

Evidence of involvement of GIGFY2 in nervous system functioning across the regulation of signaling processes at the endocytic pathway was due of experiments on animal knockout showing neurodegeneration features but without significant implication in PD pathogenesis [ ].

PARK 14 Another extrapyramidal phenotype with dystonic features, pyramidal syndrome, cognitive and psychiatric troubles was reported in three patients of two inbred Pakistani families with homozygous mutations in phospholipase A2 gene PLA2G6 located on chromosome 22q Phenotypic differences were reported in an Asian cohort with very early-onset recessive Parkinsonism, frontotemporal lobar atrophy and dementia provoked by compound heterozygous PLA2G6 mutations [ ].

PLA2G6 loss of function is at the origin of cellular proteins accumulation and apoptosis in response to oxidative stress [ ]. PARK15 The pallido-pyramidal syndrome PPS with very early onset, extrapyramidal bradykinesia, rigidity, less often tremorpyramidal signs, sometimes cerebellar features and good response to L-dopa [ ] was described by Davison in [ ] and is linked to chromosome 22q A whole genome analysis in a large Iranian family has found a homozygous FBXO7 variation confirming its putative role [ ].

FBXO7 codes for an SCF E3 ubiquitin protein ligase involved in the ubiquitin-proteasome pathway in order to preserve proteins homeostasis [ ]. PARK16 This locus was identified on chromosome 1q32 following the approach of genome wide association study GWAS and two replication studies in more than Japanes patients [ ].

A case-control Scandinavian study of individuals found evidence for an association with PD for a coding variant located around the 5' region of RAB7L1 [ ]. The protective effect of the PARK16 locus especially in older compared to younger patients and sporadic PD was suggested [ ]. The genomic analysis of an Austrian family with 7 affected individuals subsequently led to the identification of a missense mutation in the VPS35 gene segregating with late-onset PD [ ].

VPS35 is a central component of the membrane protein-recycling retromer complex, involved in retrieval of transmembrane cargo proteins from endosomes [ ]. The pathogenic mechanism of missense variants of VPS35, including DN is consistent with partial loss of function [ ] and involve mitochondrial dysfunction by recycling dynamin-like protein DLP1 complexes [ ]. PARK18 PARK18 was identified as a risk factor in a genome-wide association study of a northern French family with autosomaldominant late-onset Parkinsonism on the chromosome 3qq The phenotype of the affected subjects was typical for PD and idiopathic Lewy body disease.

A pathogenic mutation was also found in all affected members of another multiplex unrelated family, but also in one unaffected year-old family member which implies incomplete penetrance [ ]. Dysruption of the EIF4F translation initiation complex may cause a dominant-negative loss of function and neurotoxicity via oxidative stress [ ]. However, EIF4G1 is not considered a common risk factor for Parkinson's disease at least in the European cohorts [ ].

HLA region vA genome-wide association study of 2, Parkinson's disease patients from North America identified a novel risk factor in HLA region [ ] replicated in a French cohort [ ]. A functional hypothesis of HLA involvement in PD pathogenesis is via gene regulation [ ] or chronic inflammation [ ]. GBA mutations were reported in early onset PD with higher incidence in Jews families and represent an important risk factor for PD in this population [ ].

The GBA mutations carrier frequency estimated at Comorbidity of PD and Gaucher disease was also noted [ ]. The clinical expression is variable ranging from a mild L-dopa responsive idiopathic PD phenotype and Lewy body dementia [ ]. The proposed theories which confer increased risk of Parkinsonism to Gaucher carriers include gainof- function of mutant glucocerebrosidase proteins associated with deficiency in the autophagic-lysosomal pathway [ ]. MAPT The gene localized on chromosome 17q21 codes for microtubuleassociated protein tau MAPTa phosphorylated protein with essential role in maintaining the integrity of the cytoskeleton and axonal transport in neurons [ ].

Genomic screen of individuals from families yielded significant evidence of association for allelic and haplotype association with tau [ ].

can depression be genetic yahoo dating

LP multiplies by 9 the risk to develop PD. These findings were replicated in Ashkenazi Jewish population [ ] but not in an Asian cohort [ ]. Two more families with different homozygous DNAJC6 mutations segregating with PD and different phenotype with slow disease progression and dopa-sensibility were identified recently [ ]. RAB39B A large deletion including RAB39B gene led to identification of a causal relationship with early-onset Parkinsonism and intellectual disability in 3 members of an Australian kindred with X-linked dominant transmission.

The same phenotype was described in an unrelated Wisconsin family presenting a missense mutation in RAB39B [ ]. A novel missense mutation in the RAB39B gene was identified in a large family with a mean age at onset of MACF1 is active during brain development by regulating microtubule dynamics signaling in order to determine neuronal positioning [ ].

TMEM Very recently, another gene with role in synaptic vesicle trafficking involved in pathogenesis of PD was identified on chromosome 20pter-p12 [ ].

VPS13C Genetic findings strongly suggest that VPS13C vacuolar protein sorting 13C mutations may contribute to early-onset Parkinsonism with severe phenotype including cognitive deterioration and accelerated disease progression. VPS13C is a protein of mitochondrial membrane with role in maintaining of mitochondrial membrane potential and conformation [ ].

PODXL An implication of a neurodevelopmental pathway in pathogenesis of PD is supporting by the genetic analysis of two affected siblings that harbor a homozygous frameshift mutation, in PODXL podocalyxin-like genea neural adhesion molecule, located on chromosome 7q [ ].

Synphilin-IA might constitute a genetic risk factor for the development of parkinsonism seen that a putative mutation has been identified as segregating with PD in two patients with late-onset PD [ ]. Tyrosine hydroxylase The genome-wide association study found a deletion in tyrosine hydroxylase, enzyme involved in dopamine synthesis, in one adult PD [ ] whereas missense mutations in tyrosine hydroxylase gene were already involved in infantile parkinsonism [ ].

Advances in genetic field especially in Mendelien's forms of PD have given insights into molecular mechanisms critical to develop new disease-modifying therapies. Recent data provide evidence for new molecular pathways involving neurodevelopmental mechanisms [], modulating the signaling processes at the endocytic pathway [ ], synaptic vesicles endocytosis and trafficking in PD pathogenesis [], maintaining the integrity of the cytoskeleton and axonal transport in neurons [ ].

Genes' Products Relations and Mechanisms Implicated in Mendelien's forms of PD The interactions among genes' products may be an important event of molecular mechanisms involved in the pathogenesis of PD. These multiples protein substrates are intervening in a fine tuning molecular system in order to provide normal dopaminergic cells function. In favor of the mitochondrial dysfunction plead the identification of pathological cells harboring large quantities of mitochondrial DNA deletions [ ].

A hypothesis which has been advanced to explain the mitochondrial dysfunction when parkinsonian features were signaled in designer drug abusers [ ] was the inhibitory effect of MPTP on mitochondrial complex 1 of the electron transporter chain [ ], functionally linked with mitochondrial DNA mutations [], sustained by the extrapyramidal phenotype induction in animal models by inhibitors of mitochondrial complex l [ ]. VPS13C as a mitochondrial membrane protein interacts with PINK1 and Parkin in order to provide the mitochondrial morphology and membrane potential integrity [ ].

Beside mitochondrial dysfunction, the impaired pathways involved in clearing abnormal cellular proteins and damaged organelles, the ubiquitin-proteasome system and the autophagic pathway involving lysosomal activity [ 30] play a crucial role in PD etiology. Lysosomal storage disorders such as Gaucher disease have a possible functional link with PD through participation of parkin at the degradation of mutant glucocerebrosidase [ ].

Beside glucocerebrosidase, another lysosomal enzyme SMPD1 intervene in maintaining the lysosome-mediated autophagy normal function [ ]. Parkin and PINK1 functions are strictly linked in key molecular pathways to provide mitochondrial function and morphology regulation [ 52 ] by stimulating fission and inhibiting fusion [ 76] and eliminate damaged mitochondria through mitophagy [ ].

Parkin mutations altered mitophagy and PINK1 mutations the degradation of damaged mitochondria [ 53 ] that possess neurotoxic effect [ ]. VPS35 genetically and functionally interacts with parkin in order to provide mitochondrial homeostasis [ ] and with EIF4G1 in order to prevent accumulation of dysfunctional proteins and therefore neurotoxicity [ ].

PINK1 recruit parkin through phosphorylation of ubiquitin in order to eliminate the impaired mitochondria [ ].

Mechanisms Implicated in Parkinson Disease from Genetic Perspective | Insight Medical Publishing

Surprisingly, the triple inactivation of genes of parkin, DJ-1 and PINK1 did not disturb the function and morphology of dopaminergic cells nor diminish the levels of dopamine. Therefore is clear that inactivation of these PD genes involved in autosomal recessive transmission is not sufficient to induce nigral degeneration and not indispensable for the survival [ ].

Most of the sporadic cases of PD do not have a clear genetic etiology and GWAS availability is limited by the insufficiency of the significant effect size risk alleles [ ].

However, even a modest effect on PD risk is noted for each variant taken alone, their global effect could have a significant impact [ ]. Confirmation by high-throughput sequencing of loci already implicated in PD pathogenesis with increased risk for late onset PD supports the idea that familial disease are etiologically related to sporadic PD because of the functional equivalence among genes with common risk variants and rare familial PD mutations.

Therefore, pathogenesis of PD is based upon interaction between genetic susceptibility and the environmental exposure. Multiple environmental factors inducing oxidative stress and mitochondrial damage coupled to impairment of molecular mechanisms concerning the neuroprotective and autophagic activities shall be responsible for dopaminergic neurons death.

Understanding the molecular mechanisms following the identification of genes mutations and low-penetrance susceptibility alleles in familial and sporadic PD patients by genotyping technology and functional studies represent an essential step for the development of more adequate biomarkers and potent therapies with neuroprotective effects.

N Engl J Med Gowers W A manual of diseases of the nervous system. Parkinson disease in twins: J Am Med Assoc International Human Genome Sequencing Consortium Finishing the euchromatic sequence of the human genome. Proc Natl Acad Sci Volles MJ, Lansbury PT Jr Vesicle permeabilization by protofibrillar alpha-synuclein is sensitive to Parkinson's disease-linked mutations and occurs by a pore-like mechanism.

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