Psychiatric Manifestations of Voltage-Gated Potassium-Channel Complex Autoimmunity

Somers, Kristin J.; Lennon, Vanda A.; Rundell, James R.; Pittock, Sean J.; Drubach, Daniel A.; Trenerry, Max R.; Lachance, Daniel H.; Klein, Christopher J.; Aston, Paula A.; McKeon, Andrew

doi:10.1176/appi.neuropsych.23.4.425

Cited by 7 publications

(11 citation statements)

References 24 publications

(39 reference statements)

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“…Therefore, they are better termed “VGKC complex” antibodies ( Kayser and Dalmau, 2011; Lin et al, 2012). The psychiatric symptoms present in patients with VGKC autoimmunity include panic attacks, obsessive–compulsive behaviors, and cognitive alterations ( Irani and Vincent, 2011; Somers et al, 2011). …”

Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

“…Limbic encephalitis, a prototypic autoimmune neuropsychiatric disorder, is recognized by neurologists and psychiatrists by its subacute onset and rapid progression of cognitive, mood, and behavioral symptoms ( Kitten et al, 2011; Somers et al, 2011). Classically, symptoms evolve over days to weeks and include psychiatric manifestations as diverse as irritability, depression, hallucinations, and personality disturbances, with neurocognitive changes in the form of short-term memory loss, sleep disturbances, and seizures ( Kayser and Dalmau, 2011).…”

Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

“…Classically, symptoms evolve over days to weeks and include psychiatric manifestations as diverse as irritability, depression, hallucinations, and personality disturbances, with neurocognitive changes in the form of short-term memory loss, sleep disturbances, and seizures ( Kayser and Dalmau, 2011). Somers et al (2011) described the neuropsychiatric spectrum of Kv channel complex autoimmunity among 67 seropositive patients and found a significant correlation between severe neuropsychiatric presentations (such as confusion, memory impairment, personality change, depression, anxiety, visual hallucinations, delusions, and sleep disorders) and higher autoantibody values. Of 15 who received immunotherapy, 67% improved.…”

Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

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Major channels involved in neuropsychiatric disorders and therapeutic perspectives

Imbrici¹,

Camerino²,

Tricarico³

2013

Front. Genet.

121

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Voltage-gated ion channels are important mediators of physiological functions in the central nervous system. The cyclic activation of these channels influences neurotransmitter release, neuron excitability, gene transcription, and plasticity, providing distinct brain areas with unique physiological and pharmacological response. A growing body of data has implicated ion channels in the susceptibility or pathogenesis of psychiatric diseases. Indeed, population studies support the association of polymorphisms in calcium and potassium channels with the genetic risk for bipolar disorders (BPDs) or schizophrenia. Moreover, point mutations in calcium, sodium, and potassium channel genes have been identified in some childhood developmental disorders. Finally, antibodies against potassium channel complexes occur in a series of autoimmune psychiatric diseases. Here we report recent studies assessing the role of calcium, sodium, and potassium channels in BPD, schizophrenia, and autism spectrum disorders, and briefly summarize promising pharmacological strategies targeted on ion channels for the therapy of mental illness and related genetic tests.

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Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

Section: Neuropsychiatric Disorders Associated To Ion Channels Dysfunmentioning

confidence: 99%

See 1 more Smart Citation

Major channels involved in neuropsychiatric disorders and therapeutic perspectives

Imbrici¹,

Camerino²,

Tricarico³

2013

Front. Genet.

121

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“…CASPR2 antibodies, meanwhile, are associated with neuromyotonia or Morvan's syndrome in which psychiatric features are common, often with a thymoma (Irani et al, 2010a). In a case series, over a third of patients with VGKC-complex antibodies had psychiatric symptoms, including confusion, personality change, memory impairment and depression (Somers et al, 2011). Those affected are classically older than those with NMDAR antibody encephalitis.…”

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confidence: 99%

Brain-relevant antibodies in first-episode psychosis: a matched case–control study

et al. 2017

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Abstract:There has been much recent excitement about the possibility that some cases of psychosis may be wholly due to brain-reactive antibodies, with antibodies to N-Methyl-D-Aspartate receptor(NMDAR) and the voltage gated potassium channel(VGKC)-complex reported in a few patients with first episode psychosis(FEP). Methods Participants were recruited from psychiatric services in South London,UK, from 2009-2011 as part of the Genetics and Psychosis(GAP)study. We conducted a case control study to examine NMDAR and VGKC-complex antibody levels and rates of antibody positivity in 96 patients presenting with FEP and 98 controls matched for age and sex.LGI1 and CASPR antibodies were also measured. Notably,patients with suspicion of organic disease were excluded. Results Powered by Editorial Manager® and ProduXion Manager® from Aries Systems CorporationVGKC-complex antibodies were found in both cases(n=3) and controls(n=2). NMDAR antibody positivity was seen in one case and one control. Either LGI1-Abs or CASPR2-Abs were found in three cases and three controls. Neuronal antibody staining, consistent with the above results or indicating potential novel antigens, was overall positive in four patients but also in six controls. Overall, antibody positivity was at low levels only and not higher in cases than in controls. Conclusions This case-control study of the prevalence of antibodies in FEP does not provide evidence to support the hypothesis that FEP is associated with an immune-mediated process in a subgroup of patients. Nevertheless, as other bio-clinical factors may influence the effect of such antibodies in a given individual, and patients with organic neurological disease may be misdiagnosed as FEP, the field requires more research to put these findings in context. Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation

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“…In a case series of 67 consecutive patients with VGKC antibodies, 24 had a particularly florid neuropsychiatric presentation, of whom 62% had either anxiety or depression 34. In all cases, this was in the context of other symptoms, usually confusion, memory loss and seizures in 13/24.…”

Section: Mood and Psychotic Disorders And Vgkcc Antibodiesmentioning

confidence: 99%

Emerging psychiatric syndromes associated with antivoltage-gated potassium channel complex antibodies

Prüß

Lennox

2016

J Neurol Neurosurg Psychiatry

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Antibodies against the voltage-gated potassium channel (VGKC) were first recognised as having a potential pathogenic role in disorders of the central nervous system in 2001, with VGKC antibodies described in patients with limbic encephalitis, and the subsequent seminal paper describing the clinical phenotype and immunotherapy treatment responsiveness in 13 patients with VGKC antibodies and limbic encephalitis in 2004. These initial case descriptions were of a progressive neuropsychiatric syndrome with abnormalities of mood, sleep and cognition recognised alongside the neurological symptoms of seizures and autonomic instability. The clinical syndromes associated with VGKC complex (VGKCC) antibodies have broadened considerably over the last 15 years, with multiple cases of more restricted 'formes fruste' presentations associated with VGKCC antibodies being described. However, the relevance of antibodies in these cases has remained controversial. The understanding of the pathogenic nature of VGKC antibodies has further advanced since 2010 with the discovery that VGKC antibodies are not usually antibodies against the VGKC subunits themselves, but instead to proteins that are complexed with the potassium channel, in particular leucine-rich, glioma-inactivated protein 1 (LGI1) and contactin-associated protein 2 (Caspr2). Antibodies against these proteins have been associated with particular, although overlapping, clinical phenotypes, each also including neuropsychiatric features. Our aim is to critically review the association between VGKCC, LGI1 and Caspr2 antibodies with isolated psychiatric presentations-with a focus on cognitive impairment, mood disorders and psychosis. We recommend that screening for VGKCC, LGI1 and Caspr2 antibodies be considered for those with neuropsychiatric presentations.

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Psychiatric Manifestations of Voltage-Gated Potassium-Channel Complex Autoimmunity

Cited by 7 publications

References 24 publications

Major channels involved in neuropsychiatric disorders and therapeutic perspectives

Major channels involved in neuropsychiatric disorders and therapeutic perspectives

Brain-relevant antibodies in first-episode psychosis: a matched case–control study

Emerging psychiatric syndromes associated with antivoltage-gated potassium channel complex antibodies

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