Evidence for Association of an <i>ACCN1</i> Gene Variant with Response to Lithium Treatment in Sardinian Patients with Bipolar Disorder
PharmacogenomicsPublished 3 October 2011Open access
Alessio Squassina, Mirko Manchia, Joseph Borg, Donatella Congiu, Marta Costa, Marianthi Georgitsi
Citations87
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
The results indicate that ACCN1 gene is a potential candidate for response to lithium treatment that would serve as a genetic marker of lithium efficacy for BD patients.
Abstract
Our results indicate that ACCN1 gene is a potential candidate for response to lithium treatment that would serve as a genetic marker of lithium efficacy for BD patients.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
The American Journal of Human GeneticsPLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
36,140 Citations2007Shaun Purcell, Benjamin M. Neale +9 more
This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
BioinformaticsHaploview: analysis and visualization of LD and haplotype maps
14,738 Citations2004Jeffrey C. Barrett, Ben Fry +2 more
Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.
The American Journal of Human GeneticsGCTA: A Tool for Genome-wide Complex Trait Analysis
9,281 Citations2010Jian Yang, Sang Lee +2 more
The GCTA software is a versatile tool to estimate and partition complex trait variation with large GWAS data sets and focuses on the function of estimating the variance explained by all the SNPs on the X chromosome and testing the hypotheses of dosage compensation.
NatureFinding the missing heritability of complex diseases
8,405 Citations2009Teri A. Manolio, Francis S. Collins +25 more
Archives of General PsychiatryA Diagnostic Interview
5,709 Citations1978Jean Endicott
Initial scale development and reliability studies of the items and the scale scores are reported on.
Archives of General PsychiatryLifetime and 12-Month Prevalence of Bipolar Spectrum Disorder in the National Comorbidity Survey Replication
2,373 Citations2007Kathleen R. Merikangas, Hagop S. Akiskal +5 more
This study presents the first prevalence estimates of the BPD spectrum in a probability sample of the United States, and finds subthreshold BPD is common, clinically significant, and underdetected in treatment settings.
Nature GeneticsCollaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder
1,258 Citations2008Manuel A. R. Ferreira, Michael O‘Donovan +60 more
The results suggest that ion channelopathies may be involved in the pathogenesis of bipolar disorder and found further support for the previously reported CACNA1C.
NeuronThe Acid-Activated Ion Channel ASIC Contributes to Synaptic Plasticity, Learning, and Memory
658 Citations2002John A. Wemmie, Jianguo Chen +9 more
It is found that eliminating the acid sensing ion channel (ASIC) abolished H(+)-gated currents in hippocampal neurons, and null mice displayed defective spatial learning and eyeblink conditioning.
NatureA common mechanism of action for three mood-stabilizing drugs
625 Citations2002Robin S. B. Williams, Lili Cheng +2 more
It is shown that all three lithium, carbamazepine and valproic acid drugs inhibit the collapse of sensory neuron growth cones and increase growth cone area, suggesting a molecular basis for both bipolar affective disorder and its treatment.
Trends in NeurosciencesAcid-sensing ion channels: advances, questions and therapeutic opportunities
534 Citations2006John A. Wemmie, Margaret P. Price +1 more
Advances in understanding of acid-sensing ion channels, their potential contributions to disease, and the possibility for their therapeutic modification are reviewed.
The Journal of Clinical PsychiatryIs Response to Prophylactic Lithium a Familial Trait?
423 Citations2002Paul Grof, Anne Duffy +6 more
This highly significant difference in response between relatives and the control group supports the view that the response to lithium prophylaxis clusters in families is a familial trait.
The EMBO JournalThe heterotetrameric architecture of the epithelial sodium channel (ENaC)
409 Citations1998Dmitri Firsov, Ivan Gautschi +3 more
Bipolar DisordersThe role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis
364 Citations2009Rodrigo Machado‐Vieira, Husseini K. Manji +1 more
The evidence reviewed here suggests that lithium's neurotrophic effects in BD are an example of an old molecule acting as a new proof-of-concept agent, which will likely lead to the development of not only improved therapeutics for BD, but to neurotrophic enhancers that could prove useful in the treatment of many other illnesses.
NeuropsychopharmacologyIs Glycogen Synthase Kinase-3 a Central Modulator in Mood Regulation?
295 Citations2010Xiaohua Li, Richard S. Jope
Evidence from animal biochemical, pharmacological, molecular, and behavioral studies and from human post-mortem brain, peripheral tissue, and genetic studies support the conclusion that bolstering the inhibitory control of GSK3 is an important component of the therapeutic actions of drugs used to treat mood disorders and that G SK3 is a valid target for developing new therapeutic interventions.
Nature GeneticsA locus for bipolar affective disorder on chromosome 4p
264 Citations1996Douglas Blackwood, Lin He +12 more
A linkage stud in twelve bipolar families, carrying out a single family genome search employing 193 markers indicate linkage on chromosome 4p where the marke D4S394 generated a two-point lod score under a dominant model of inheritance.
Bipolar DisordersGlycogen synthase kinase‐3β, mood stabilizers, and neuroprotection
244 Citations2002Xiaohua Li, Gautam N. Bijur +1 more
It is demonstrated that several drugs therapeutic for bipolar disorder can provide neuroprotection by inhibiting the pro-apoptotic effects of GSK-3beta, providing new evidence that dysregulation of G SK-3 beta may contribute to the pathophysiology of bipolar disorder.
Human Molecular GeneticsReplication and extension of genome-wide association study results for obesity in 4923 adults from northern Sweden
229 Citations2009Frida Renström, Felicity Payne +7 more
Six of the previously associated obese-risk loci are statistically replicated and the results suggest that the weight-inducing effects of these variants are explained largely by increased adipose accumulation.
Journal of Biological ChemistryAcid-sensing Ion Channel 2 (ASIC2) Modulates ASIC1 H+-activated Currents in Hippocampal Neurons
222 Citations2004Candice C. Askwith, John A. Wemmie +3 more
It is found that the absolute and relative amounts of ASIC subunits determine the amplitude and properties of hippocampal H+-gated currents and therefore may contribute to normal physiology and pathophysiology.
Molecular InterventionsMOLECULAR EFFECTS of lithium
203 Citations2004J. A. Quiroz
Recent insights into lithium's actions are reviewed, leading to the strategic development of improved therapeutics for the treatment of bipolar disorder and its intracellular downstream targets including adenylate cyclase, the phosphoinositol cascade, arachidonic acid metabolism, and effects on neurotrophic cascade.
American Journal of PsychiatryGraphic representation of the life course of illness in patients with affective disorder
199 Citations1988Robert M. Post, Peter Roy‐Byrne +1 more
The authors illustrate methods for the graphic depiction of the course of unipolar and bipolar affective illness, and the utility and advantages of such an approach include accurate assessment of episode patterns and better delineation of treatment response.
Molecular PsychiatryThe genetics of bipolar disorder: genome ‘hot regions,’ genes, new potential candidates and future directions
198 Citations2008Alessandro Serretti, Laura Mandelli
The combination of linkage and association approaches provided a number of liability genes in BP, Nevertheless, other approaches are required to disentangle conflicting findings, such as gene interaction analyses, interaction with psychosocial and environmental factors and, finally, endophenotype investigations.
Journal of Affective DisordersProphylactic treatment response in bipolar disorder: Results of a naturalistic observation study
194 Citations2007Julie Garnham, Allana Munro +7 more
Lithium responders were more likely to be bipolar II, and had a typically episodic course of illness with earlier onset in comparison with non-responders, while responders to valproate had higher rates of psychosis.
Neuroscience LettersLong-term response to lithium salts in bipolar illness is influenced by the glycogen synthase kinase 3-β −50 T/C SNP
182 Citations2004Francesco Benedetti, Alessandro Serretti +5 more
Results showed that homozygotes for the wild variant did not change their recurrence index while carriers of the mutant allele improved, thus supporting the hypothesis that GSK is a target for the therapeutic action of lithium.
American Journal of PsychiatryAssociation between bipolar affective disorder and multiple sclerosis
169 Citations1986Randolph B. Schiffer, N. Margaret Wineman +1 more
Ten patients from Monroe County, N.Y., had both multiple sclerosis and bipolar affective disorder, and Epidemiologic data indicate that the expected number would be 5.4, and this difference may indicate an association between these disorders.
Molecular PsychiatryMapping susceptibility genes for bipolar disorder: a pharmacogenetic approach based on excellent response to lithium
168 Citations2001Gustavo Turecki, Paul Grof +13 more
A complete genome scan using 378 markers spaced at an average distance of 10 cM in 31 families ascertained through excellent lithium responders provided original evidence suggesting that loci on 15q14 and 7q11.2 may be implicated in the pathogenesis of BD responsive to lithium.
Archives of General PsychiatryDoes Lithium Treatment Still Work?
163 Citations2000Ross J. Baldessarini, Leonardo Tondo
Data evaluated herein did not support suggestions that benefits of lithium have been exaggerated in the past or have been lost recently, and lithium is unmatched in research support for long-term clinical effectiveness against morbidity and mortality associated with depression or mania in bipolar I and II disorders.
American Journal of PsychiatryA Genomewide Association Study of Response to Lithium for Prevention of Recurrence in Bipolar Disorder
160 Citations2009Roy H. Perlis, Jordan W. Smoller +10 more
Multiple novel loci merit further examination for association with lithium response in bipolar disorder patients, including one region that spans the GRIA2 gene, for which expression has been shown to be regulated by lithium treatment.
Journal of Affective DisordersLithium response and genetics of affective disorders
160 Citations1994Paul Grof, Martin Alda +3 more
Both family history and the proband's diagnosis contribute independently to predicting response to long-term lithium response, and there were no significant differences in the rates of other psychiatric disorders.
Journal of NeuroscienceAcid-Sensing Ion Channel-1a in the Amygdala, a Novel Therapeutic Target in Depression-Related Behavior
159 Citations2009Matthew W. Coryell, Amanda M. Wunsch +12 more
Testing several behavioral tests in rodents used to test the hypothesis that the acid-sensing ion channel-1a (ASIC1a) might be targeted to reduce depression suggested that ASIC1a antagonists may effectively combat depression.
Human Molecular GeneticsLocalization of a gene for Mobius syndrome to chromosome 3q by linkage analysis in a Dutch family
147 Citations1996Hannie Kremer
L linkage analysis in a large family with autosomal dominantly inherited Möbius syndrome, consisting essentially of asymmetric bilateral facial pareses, localized the gene to chromosome 3q21-22, indicating genetic heterogeneity of MöBius syndrome.
Journal of Biological ChemistryNumber of Subunits Comprising the Epithelial Sodium Channel
134 Citations1999Sepehr Eskandari, Peter M. Snyder +4 more
The freeze-fracture electron microscopy and electrophysiological methods suggest that functional ENaC consists of eight or nine subunits of which a minimum of two are γ subunits.
Molecular PsychiatryEvidence for a role of phospholipase C-γ1 in the pathogenesis of bipolar disorder
129 Citations1998Gustavo Turecki, Paul Grof +22 more
Preliminary evidence is provided that a PLC isozyme that codes for a γ-1 isozyme of phospholipase (PLC) may confer susceptibility to bipolar disorder, probably accounting for a fraction of the total genetic variance.
Molecular PsychiatryEvidence for a putative bipolar disorder locus on 2p13–16 and other potential loci on 4q31, 7q34, 8q13, 9q31, 10q21–24, 13q32, 14q21 and 17q11–12
123 Citations2003J Liu, Suh‐Hang Hank Juo +14 more
This systematic, large-scale study identified novel putative loci for BP (on 2p13–16, 8q13 and 14q21) and found support for previously proposed loci (on 4q31, 7q34, 9Q31, 10q21–24, 13q32 and 17q11–12).
Cancer ResearchRASSF4/AD037 Is a Potential Ras Effector/Tumor Suppressor of the RASSF Family
118 Citations2004Kristin Eckfeld, Luke B. Hesson +4 more
RASSF4 appears to be a new member of the RASSF family of potential Ras effector/tumor suppressors, which binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effectors.
The Pharmacogenomics JournalSerotonin transporter gene associated with lithium prophylaxis in mood disorders
114 Citations2001Alessandro Serretti, Roberta Lilli +3 more
5-HTTLPR variants may be a possible influencing factor for the prophylactic efficacy of lithium in mood disorders and subjects with the s/s variant showed a worse response compared to both l/s and l/l variants.
Trends in NeurosciencesMolecular neurobiology of bipolar disorder: a disease of ‘mood-stabilizing neurons’?
104 Citations2008Tadafumi Kato
Genes Brain & BehaviorMolecular genetics of bipolar disorder
102 Citations2005Elizabeth P. Hayden, John I. Nürnberger
An overview of linkage studies of BPD is given, concluding that the regions with the best evidence for linkage include areas on chromosomes 2p, 4p,4q, 6q, 8q, 11p, 12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and Xq.
Neuroscience LettersAssociation study of the INPP1, 5HTT, BDNF, AP-2β and GSK-3β GENE variants and restrospectively scored response to lithium prophylaxis in bipolar disorder
102 Citations2006Leandro Michelon, Ivanor Meira‐Lima +5 more
These investigated variants are not predictive factors for lithium prophylactic response in the sample of bipolar disorder type I patients, however, it is still possible that a subgroup of a diverse ethnic ancestry may be predisposing to some of those variants for lithium response.
Journal of Cerebral Blood Flow & MetabolismAcid-Sensing Ion Channels in Acidosis-Induced Injury of Human Brain Neurons
96 Citations2010Minghua Li, Kōichi Inoue +6 more
It is shown that a decrease in the extracellular pH evoked inward currents characteristic of acid-sensing ion channels (ASICs) and increased intracellular Ca2+ in cultured human cortical neurons.
PharmacogeneticsThe polymorphic inositol polyphosphate 1-phosphatase gene as a candidate for pharmacogenetic prediction of lithium-responsive manic-depressive illness
91 Citations1998Vidar M. Steeir, Roger L vlie +4 more
DNA variations in the human INPP1 gene encoding the inositol polyphosphate 1-phosphatase enzyme are searched for and the existence of four common polymorphisms in the coding region of the gene is reported.
Molecular InterventionsLooking at Lithium: Molecular Moods and Complex Behaviour
81 Citations2008Jean‐Martin Beaulieu, M. G. Caron
An overview of recent advances in the identification of molecular mechanisms involved in the regulation of behavior by lithium is provided and recent findings suggesting that lithium could exert some of its behavioral effects by acting on a dopamine receptor regulated signaling complex composed of Akt, protein phosphatase 2A, and the multifunctional protein scaffold beta-arrestin 2 are highlighted.
PharmacogenomicsAssociation Studies of the <i>BDNF</i> and the <i>NTRK2</i> Gene Polymorphisms with Prophylactic Lithium Response in Bipolar Patients
80 Citations2008Monika Dmitrzak‐Węglarz, Janusz Rybakowski +5 more
A relationship between response to lithium prophylaxis and polymorphisms of two functionally connected genes: BDNF and NTRK2, in bipolar illness is described.
Molecular PsychiatryThe Wellcome trust UK–Irish bipolar affective disorder sibling-pair genome screen: first stage report
72 Citations2002Philip C. Bennett, Ricardo Segurado +20 more
The first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage.
Progress in Neuro-Psychopharmacology and Biological PsychiatryInvestigating responders to lithium prophylaxis as a strategy for mapping susceptibility genes for bipolar disorder
71 Citations2005Martin Alda, Paul Grof +3 more
The available evidence strongly suggests that lithium-responsive bipolar disorder is the core bipolar phenotype, characterized by a more prominent role of genetic factors.
PubMedProphylactic effect of lithium in bipolar affective illness may be related to serotonin transporter genotype.
70 Citations2005Janusz Rybakowski, Aleksandra Suwalska +4 more
A supposition is made that prophylactic management of bipolar illness can be optimized by defining 5-HTTLPR genotype, and an association of S genotype with worse response to serotonergic drugs is shown.
Journal of Psychiatric ResearchSerotonin receptor 2A, 2C, 1A genes and response to lithium prophylaxis in mood disorders
67 Citations2000Alessandro Serretti, Cristina Lorenzi +2 more
5-HT2A and 2C variants are not, therefore, associated with lithium prophylactic efficacy in mood disorders and are not connected with lithium treatment.
Bipolar DisordersMaintenance treatment in bipolar disorder: a reassessment of lithium as the first choice
63 Citations2009William Coryell
The evidence reviewed here strongly supports the consideration of lithium when prophylactic treatment is first begun for a bipolar patient.
Acta Psychiatrica ScandinavicaLithium – a continuing story in the treatment of bipolar disorder
58 Citations2005S. Carney, G M Goodwin
The literature on the use of lithium in the treatment of bipolar disorder is reviewed and the evidence base supporting its efficacy and safety is highlighted.
The International Journal of NeuropsychopharmacologyDopamine receptor D3 gene and response to lithium prophylaxis in mood disorders
50 Citations1998Alessandro Serretti, Roberta Lilli +3 more
The aim of this study was to investigate the association between the dopamine receptor D3 (DRD3) gene and prophylactic efficacy of lithium in mood disorders, and found that DRD3 variants were not associated with lithium outcome.
European Journal of EndocrinologyGenetic variants associated with persistent central obesity and the metabolic syndrome in a 12-year longitudinal study
43 Citations2010Chloe Y. Y. Cheung, Annette W.K. Tso +8 more
It is demonstrated that FTO and GNPDA2 variants predicted persistent central obesity in the Chinese population, further supporting their importance as obesity-susceptible genes.
Neuroscience LettersInteracting genes in lithium prophylaxis: Preliminary results of an exploratory analysis on the role of DGKH and NR1D1 gene polymorphisms in 199 Sardinian bipolar patients
41 Citations2009Mirko Manchia, Alessio Squassina +5 more
The findings do not exclude an involvement of DGKH and NR1D1 in lithium prophylaxis, but the lack of statistic interaction might not necessarily correspond to a lack of biologic interaction between the genes studied.
PLoS ONEAssociation between the ACCN1 Gene and Multiple Sclerosis in Central East Sardinia
39 Citations2007Luisa Bernardinelli, Salvatore Bruno Murgia +11 more
A method of analysis where complete, phase-solved, posterior-weighted haplotype assignments are imputed for each study individual from incomplete, multi-locus, genotyping data is developed, finding a significant association between MS and the SNP rs28936 located in the 3′ UTR segment of ACCN1.
CNS SpectrumsGenetic Linkage in Bipolar Disorder
30 Citations2003Carol A. Mathews, Victor I. Reus
The strongest evidence suggests that bipolar disorder susceptibility loci may lie in one or more genomic regions on chromosomes 18, 4, and 21, as well as those on chromosomes 5 and 8, which are also under investigation.
Pharmacological ResearchThe PDLIM5 gene and lithium prophylaxis: An association and gene expression analysis in Sardinian patients with bipolar disorder
30 Citations2008Alessio Squassina, Donatella Congiu +6 more
A number of studies support the notion that lithium interacts with the protein kinase C (PKC) pathway, an important mediator of several intracellular responses to neurotransmitter signaling, but whether PDLIM5 expression interacts with lithium response is questionable.
European Journal of Human GeneticsRefinement of the locus for hereditary congenital facial palsy on chromosome 3q21 in two unrelated families and screening of positional candidate genes
29 Citations2006Caroline B. Michielse, Meena Bhat +7 more
Human Genomics and ProteomicsPharmacogenomics of Mood Stabilizers in the Treatment of Bipolar Disorder
22 Citations2010Alessio Squassina, Mirko Manchia +1 more
While the results provided so far support the key role of genetic factors in modulating the response phenotype, strong evidence for genetic predictors is still lacking and further research efforts are needed to facilitate implementation of pharmacogenomics into clinical settings.