Variations in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) are Associated with Bipolar I Disorder

Lohoff, Falk W.; Dahl, John P.; Ferraro, Thomas N.; Arnold, Steven E.; Gallinat, Jürgen; Sander, Thomas; Berrettini, Wade H.

doi:10.1038/sj.npp.1301196

Cited by 63 publications

(63 citation statements)

References 72 publications

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“…This was substantiated by Basselin et al (2006), who demonstrated that lithium reduced D 2 -like-receptor-initiated signaling in a number of brain regions, including the substantia nigra. Additionally, genetic expression studies have linked the vesicular monoamine transporter gene, which is associated with BD, to the substantia nigra, where it is expressed at higher levels than any other brain region (Lohoff et al, 2006). Thus our results suggest a link between brain structural and dopaminergic changes associated with mania.…”

Section: Brain Structural Changes Associated With the Diagnosis Of Bdmentioning

confidence: 48%

Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder

Kempton¹,

Haldane²,

Jogia³

et al. 2009

J. Neurosci.

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Genetic factors are important in the etiology of bipolar disorder (BD). However, first-degree relatives of BD patients are at risk for a number of psychiatric conditions, most commonly major depressive disorder (MDD), although the majority remain well. The purpose of the present study was to identify potential brain structural correlates for risk and resilience to mood disorders in patients with BD, type I (BD-I) and their relatives. Structural magnetic resonance imaging scans were acquired from 30 patients with BD-I, 50 of their firstdegree relatives (28 had no Axis I disorder, while 14 had MDD) and 52 controls. We used voxel-based morphometry, implemented in SPM5 to identify group differences in regional gray matter volume. From the identified clusters, potential differences were further examined based on diagnostic status (BD-I patients, MDD relatives, healthy relatives, controls). Whole-brain voxel-based analysis identified group differences in the left hemisphere in the insula, cerebellum, and substantia nigra. Increased left insula volume was associated with genetic preposition to BD-I independent of clinical phenotype. In contrast, increased left substantia nigra volume was observed in those with the clinical phenotype of BD-I. Changes uniquely associated with the absence of a clinical diagnosis in BD relatives were observed in the left cerebellum. Our data suggest that in BD, genetic and phenotype-related influences on brain structure are dissociable; if replicated, these findings may help with early identification of high-risk individuals who are more likely to transition to syndromal states.

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Section: Brain Structural Changes Associated With the Diagnosis Of Bdmentioning

confidence: 48%

Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder

Kempton¹,

Haldane²,

Jogia³

et al. 2009

J. Neurosci.

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“…For rs 2270641, T allele was observed as the minor allele with an allele frequency of 0.480 in Emirati population whilst this allele was found to be major allele in all the Hapmap population (Table 2). However, Lohoff et al (2006) reported T allele as the minor allele with a frequency of 0.35 in a European population but significantly different from Emirati population. For rs2270637, minor G allele frequency in Emirati population was not significantly different from that of the other populations on the HapMap data.…”

Section: Discussionmentioning

confidence: 99%

“…Variations in the VMAT1 gene might affect transporter function and might be involved in the etiology of neuropsychiatric disorders. Previously, the three nonsynonymous SNPs [Thr4Pro (rs2270641), Thr98Ser (rs2270637),Thr136Ile (rs1390938)] were reported to be associated with psychiatric disorders (Lohoff et al, 2008a, b;Bly, 2005;Richards et al, 2006;Chen et al, 2007) The amino acid variant Thr136Ile in the VMAT1 gene was found associated with bipolar disorder in a case control association study conducted by Lohoff et al (2006). The Thr4Pro polymorphism was associated with SZ in Europeans (Bly, 2005) and Chinese (Chen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It was thought initially that VMAT1 is expressed exclusively in neurons of the peripheral nervous system, endocrine tissue, and chromaffin cells, while only the VMAT2 isoform was thought to be expressed in the brain (Peter et al, 1993;Erickson et al, 1996;Eidenet al, 2004). However, later studies showed that VMAT1 is expressed in rat brain (Hansson et al, 1998) and human brain (Lohoff et al, 2006) as well. Since then various in-vitro and in-vivo studies demonstrated that VMAT1 is an important candidate for biological research in psychiatric disorders and genetic variants of VMAT1 were found associated with schizophrenia, bipolar disorders, anxiety and depression (Lohoff et al, 2008a, b;Berrettini, 2003).VMAT1 polymorphisms also influence monoamine signaling, the functional response of emotional brain circuits, and risk for psychopathology (Lohoff et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Genetic polymorphism of vesicular monoamine transporter 1 gene (SLC18A1) in Emirati population

Mutery¹,

Kamal²,

Bloushi³

et al. 2017

Int. J. Genet. Mol. Biol.

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Vesicular monoamine transporters (VMATs) are an important target for biological research in neuropsychiatric disorders. Recent studies indicated that VMAT1 is expressed in the brain, thus making transporter plausible candidate genes for neuropsychiatric disorders. Furthermore, several recent genetic case-control studies have documented an association between common missense variations in the VMAT1 gene and susceptibility to bipolar disorder and schizophrenia. Until now, there are no reports of VMAT 1 allele frequencies in Emirati population. Hence, the aim of the present work was to study VMAT1 genetic polymorphism in Healthy Emirati population. Saliva samples were collected from 248 healthy Emiratis and genotyping was done for rs2270641 by PCR-RFLP, and rs2270637 and rs1390938 by Taqman assay. The minor allele frequencies of rs2270641, rs2270637 and rs1390938 were 0.48, 0.20 and 0.18, respectively, which were compared with that of available HapMap population data. In conclusion, the present study is first of its kind in Emirati population that established the allele and genotype frequency for various VMAT1 alleles which can be exploited to design future studies on the genetic association of neuropsychiatry disorders.

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“…Family and twin studies show bipolar disorder has a strong heritable component (Lohoff et al, 2006). In bipolar disorder I, there is mania and major depression in ratio of 1: 3.…”

Section: Bipolar Disordermentioning

confidence: 99%

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

Oriaifo¹

2015

J. Med. Med. Sci

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The prevalence of diabetes and co-morbid diseases, especially in developing countries, may have already exceeded estimates. Accumulating reports indicate considerable underpinnings in the mechanisms of the aetiopathogenesis of metabolic syndrome, bipolar disorder, epilepsy and, recently, substance addiction. Continuing evidence incriminates dysfunction in genetic, mitochondrial and inflammatory cascade mechanisms as contributory factors to the dysregulation of neurotrophic, serotonergic, dopaminergic, adrenergic, glutamatergic, GABAergic and autophagic pathways. There may also be co-incident dysregulation of the global anti-oxidant network, the endogenous digitalis system, the vasopressin signalling and the hypothalamo-pituitary-adrenal axis. Nuclear factor-kappa B (NF-kappa B) signaling and reactive oxygen species lead to activation of the mammalian target of rapamycin complex I (mTORCI) and this process may be central to the aetiopathogenesis of drug addiction, obesity, foetal programming, diabetes mellitus, epilepsy and bipolar disorder. Antiglycaemics such as cannabinoid CB2 agonists, metformin, artesunate and valproate; insulin-mimetics such as glucagon-like peptide-I (GLP-I) and its analogues; phytomedicines from garlic and curcumin are now shown to exhibit neuroprotective effects. These agents which may down-regulate inflammatory cytokines, upregulate endothelial nitric oxide (eNOS) and peroxisome proliferator-activated receptor alpha (PPAR-α) signalling, attenuate mitochondrial dysfunction, enhance the actions of glucagon-like peptide-I (GLP-I), inhibit mTOR, NF-kappa B, interleukin-I β and glycogen synthase kinase-3 β stand to be of benefit in these illnesses which demonstrate considerable overlay in their aetopathogenic mechanisms. Underpinnings and bidirectional relationships between the metabolic syndrome and mental health disorders may pave way for common new fronts to drug development in translational cardiovascular psychiatry and neurology.

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Variations in the Vesicular Monoamine Transporter 1 Gene (VMAT1/SLC18A1) are Associated with Bipolar I Disorder

Cited by 63 publications

References 72 publications

Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder

Dissociable Brain Structural Changes Associated with Predisposition, Resilience, and Disease Expression in Bipolar Disorder

Genetic polymorphism of vesicular monoamine transporter 1 gene (SLC18A1) in Emirati population

Type 2 diabetes mellitus, drug addiction, bipolar disorder and epilepsy display overlapping aetiopathogenic mechanisms: Implication for prevention and pharmacotherapy

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