The ANK3 Bipolar Disorder Gene Regulates Psychiatric-Related Behaviors That Are Modulated by Lithium and Stress

@article{Leussis2013TheAB,
  title={The ANK3 Bipolar Disorder Gene Regulates Psychiatric-Related Behaviors That Are Modulated by Lithium and Stress},
  author={Melanie P. Leussis and Erin Berry-Scott and Mai Saito and Huei-ting Jhuang and Georgius de Haan and Ozan Alkan and Catherine J. Luce and Jon M. Madison and Pamela Sklar and Thomas Serre and David E. Root and Tracey L. Petryshen},
  journal={Biological Psychiatry},
  year={2013},
  volume={73},
  pages={683-690}
}
BACKGROUND Ankyrin 3 (ANK3) has been strongly implicated as a risk gene for bipolar disorder (BD) by recent genome-wide association studies of patient populations. However, the genetic variants of ANK3 contributing to BD risk and their pathological function are unknown. METHODS To gain insight into the potential disease relevance of ANK3, we examined the function of mouse Ank3 in the regulation of psychiatric-related behaviors using genetic, neurobiological, pharmacological, and gene… Expand
View on Elsevier
serre-lab.clps.brown.edu
76 Citations
Highly Influential Citations
4
Background Citations
26
Methods Citations
1
Results Citations
1

76 Citations

Citation Type

Citation Type

Lithium reverses behavioral and axonal transport-related changes associated with ANK3 bipolar disorder gene disruption
TLDR
It is proposed that psychiatric-related behavior in Ank3+/- mice is connected to a disturbance of the kinesin cargo system, resulting in a dysfunction of neuronal ion channel and glutamate receptor transport, suggesting the promotion of anterograde kinesIn transport as part of its mechanism of action in ameliorating Ank3-related psychiatric- related behavior. Expand
The ankyrin-3 gene is associated with posttraumatic stress disorder and externalizing comorbidity
TLDR
Findings support a role of ANK3 in risk of stress-related and externalizing disorders, beyond its previous associations with bipolar disorder and schizophrenia. Expand
AnkG hemizygous mice present cognitive impairment and elevated anxiety/depressive-like traits associated with decreased expression of GABA receptors and postsynaptic density protein
TLDR
It is possible that the loss of AnkG in the brain disrupts the excitation/inhibition balance of neurotransmitters, hindering the synaptic plasticity of neurons, and consequently leading to abnormal behavioral symptoms, and may constitute a new target for treating neuropsychiatric diseases, especially cognitive dysfunction. Expand
Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders
TLDR
The data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders, and model in humans a gene by early stress interplay on brain phenotypes during cognitive performance. Expand
Disruption of the psychiatric risk gene Ankyrin 3 enhances microtubule dynamics through GSK3/CRMP2 signaling
TLDR
The molecular effects of disrupting brain-specific Ank3 isoforms in mouse and neuronal model systems indicate that ANK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2. Expand
Disruption of The Psychiatric Risk Gene Ankyrin 3 Enhances Microtubule Dynamics Through GSK3/CRMP2 Signaling
TLDR
Data indicate that aNK3 functions in neuronal microtubule dynamics through GSK3 and its downstream substrate CRMP2, and reveals cellular and molecular mechanisms underlying brain-specific ANK3 disruption that may be related to its role in psychiatric illness. Expand
Genetic disruption of ankyrin-G in adult mouse forebrain causes cortical synapse alteration and behavior reminiscent of bipolar disorder
TLDR
A mouse model with conditional disruption of ANK3 gene in neurons in adult forebrain (Ank-G cKO) recapitulates some of the core features of human bipolar disorder and indicates that cortical microcircuitry alterations during adulthood may be involved in pathogenesis. Expand
Association analysis of ANK3 variants with bipolar disorder in the Korean population
TLDR
Haplotype analysis results suggest that ANK3 variants rs1938526 and rs10994336 may confer susceptibility for BD in the Korean population, and association analysis revealed a probable genetic difference between Korean and Caucasian populations in the degree of AnK3 involvement in BD pathogenesis. Expand
Genetic modulation of working memory deficits by ankyrin 3 gene in schizophrenia
  • Chen Zhang, Jun Cai, +8 authors Y. Fang
  • Psychology, Medicine
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry
  • 2014
TLDR
The results indicated that genetic variation within ANK3 may exert gene-specific modulating effects on working memory deficits in schizophrenia. Expand
Effects of ANK3 Variation on Gray and White Matter in Bipolar Disorder
TLDR
Findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 73 REFERENCES
Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology
TLDR
The current evidence for genetic association of ANK3 with BD is reviewed, followed by a comprehensive overview of the known biology of the ankyrin G protein, focusing on its neural functions and their potential relevance to BD. Expand
AKT Kinase Activity Is Required for Lithium to Modulate Mood-Related Behaviors in Mice
TLDR
This work modeled lithium responsiveness using cellular assays of glycogen synthase kinase 3 (GSK-3) signaling and mood-related behavioral assays in inbred strains of mice that differ in their response to lithium, and distinguished the mechanism of action of lithium from direct GSK-3 inhibition both in vivo and in vitro. Expand
The Cognitive Impact of the ANK3 Risk Variant for Bipolar Disorder: Initial Evidence of Selectivity to Signal Detection during Sustained Attention
TLDR
The results suggest that allelic variation in ANK3 impacts cognitive processes associated with signal detection and this mechanism may relate to risk for BD, however, these results require independent replication and confirmation that AnK3 (rs10994336) is a direct functional variant. Expand
Phenomic, Convergent Functional Genomic, and biomarker studies in a stress‐reactive genetic animal model of bipolar disorder and co‐morbid alcoholism
  • H. Le-Niculescu, M. McFarland, +13 authors A. Niculescu
  • Biology, Medicine
  • American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
  • 2008
TLDR
It is reported that mice with a homozygous deletion of DBP have lower locomotor activity, blunted responses to stimulants, and gain less weight over time, and that activation is prevented by treatment with the mood stabilizer drug valproate. Expand
Mood Disorder Susceptibility Gene CACNA1C Modifies Mood-Related Behaviors in Mice and Interacts with Sex to Influence Behavior in Mice and Diagnosis in Humans
TLDR
Preclinical results support a role for CACNA1C in mood disorder pathophysiology, and the combination of human genetic and preclinical data support an interaction between sex and genotype. Expand
Glycogen Synthase Kinase-3 in the Etiology and Treatment of Mood Disorders
  • R. Jope
  • Psychology, Medicine
  • Front. Mol. Neurosci.
  • 2011
TLDR
Evidence is reviewed that depression may be associated with impaired inhibitory control of GSK3, and mania by hyper-stimulation of G SK3, which provides substantial support for the hypothesis that inhibition of GK3 activity is therapeutic for mood disorders. Expand
The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis.
TLDR
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. Expand
Glycogen Synthase Kinase-3β Haploinsufficiency Mimics the Behavioral and Molecular Effects of Lithium
TLDR
It is shown that lithium therapy activates Wnt signaling in vivo, as measured by increased Wnt-dependent gene expression in the amygdala, hippocampus, and hypothalamus, which supports a central role for GSK-3β in mediating behavioral responses to lithium. Expand
The genetics of bipolar disorder
TLDR
Genomewide association analysis, which has successfully identified susceptibility genes for a variety of complex disorders, has begun to implicate specific genes for bipolar disorder (DGKH, CACNA1C, ANK3); the polygenicity of the disorder means that very large samples will be needed to detect the modest effect loci that likely contribute to bipolar disorder. Expand
Molecular and genetic evidence for abnormalities in the nodes of Ranvier in schizophrenia.
CONTEXT Genetic, neuroimaging, and molecular neurobiological evidence support the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could arise from failures of saltatory conduction… Expand
...
1
2
3
4
5
...