HL-A Antigens and the Response to Prophylactic Lithium

Perris, C.; Strandman, E.; Wählby, L

doi:10.1159/000117671

Cited by 35 publications

(13 citation statements)

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“…In 1979, Perris et al . found that the frequency of HLA‐A3 antigen was significantly higher in lithium non‐responders 59 . This relationship between HLA‐A3 antigen and non‐response to prophylactic treatment by lithium was confirmed by other researchers 7,60 , 61 .…”

Section: Human Leukocyte Antigen Typingsupporting

confidence: 68%

Biological predictors of lithium response in bipolar disorder

Ikeda

Kato

2003

Psychiatry Clin Neurosci

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In order to prescribe lithium appropriately to patients with bipolar disorder, predictors of lithium response are helpful. The present paper reviews the biological predictors of lithium response. As a positive predictor of lithium response, the following have been reported: strong loudness dependence of the auditory-evoked N1/P2-response; higher brain lithium concentration; lower inositol monophosphatase (IMPase) mRNA expression; higher serotonin-induced calcium mobilization; increased N -acetyl-aspartate peak and decreased myo-inositol peak; white matter hyperintensity; decreased intracellular pH; higher frequency of phospholipase C g -1 ( PLCG1 )-5 repeat and PLCG1 -8 repeat; and C973A polymorphism in the inositol polyphosphate 1-phosphatase gene. In contrast the following have been reported as a predictor of negative lithium response: epileptiform abnormality of electroencephalography; human leukocyte antigen type A3; decreased phosphocreatine peak area after photic stimulation; and homozygotes for the short variant of the serotonin transporter gene. Most of the possible biological predictors of better lithium response, such as lower IMPase mRNA levels, white matter hyperintensity, lower brain intracellular pH, enhanced calcium response, and PLCG1 -5 repeat had been detected as risk factors for bipolar disorder, suggesting that bipolar disorder responding well to maintenance lithium treatment is a distinct category having a certain neurobiological basis, although these findings need further replication. The search for biological predictors of lithium response is still in its infancy. Most of the laboratory or neuroimaging techniques used in these studies are not easily performed in clinical settings, so the development of an easy and useful laboratory test is needed.

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Section: Human Leukocyte Antigen Typingsupporting

confidence: 68%

Biological predictors of lithium response in bipolar disorder

Ikeda

Kato

2003

Psychiatry Clin Neurosci

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“…Differences in cellular HLA surface protein composition between BPD patients who respond well to lithium and non-responders were first reported over 30 years ago in several studies. These reports noted that leukocyte HLA-A3 antigen reactivity was reported to be associated with poor lithium response, whereas the absence of HLA-A3 predicted a favorable response [58][59][60] . At the same time, in vitro experiments suggested that lithium binds to HLA antigens on cultured human leukocytes 61 .…”

Section: Discussionmentioning

confidence: 99%

High genetic loading of schizophrenia predicts poor response to lithium in patients with bipolar disorder: A polygenic score and cross-trait genetic analysis

Amare

Schubert

Hou

et al. 2017

Preprint

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Question: Does a polygenic score for Schizophrenia (SCZ) predict response to lithium in patients with Bipolar Disorder (BPD)? What are the molecular drivers of the association between SCZ and lithium treatment response? Findings:We found an inverse association between genetic loading for SCZ risk variants and response to lithium in patients with BPD. Genetic variants in the HLA region on chromosome 6, the antigen presentation pathway and markers of inflammation (TNFα, IL-4, IFNγ) point to molecular underpinnings of lithium treatment response in BPD. Meaning:In patients with BPD, an assessment of a polygenic load for SCZ risk variants may assist in conjunction with clinical data to predict whether they would respond to lithium treatment.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/209270 doi: bioRxiv preprint first posted online Nov. 11, 2017; 10 ABSTRACT Importance: Lithium is a first-line mood stabilizer for the maintenance treatment of Bipolar Disorder (BPD). However, the efficacy of lithium varies widely, with a non-response rate of up to 30%. Biological response markers and predictors are lacking.Objective: Genetic factors are thought to mediate lithium treatment response, and the previously reported genetic overlap between BPD and schizophrenia (SCZ) led us to test whether a polygenic score (PGS) for SCZ could predict lithium treatment response in BPD.Further, we explored the potential molecular underpinnings of this association.Design: Weighted SCZ PGSs were computed at ten p-value thresholds (PT) using summary statistics from a genome-wide association study (GWAS) of 36,989 SCZ cases, and genotype data for BPD patients from the Consortium on Lithium Genetics (ConLi + Gen). For functional exploration, we performed a cross-trait meta-GWAS and pathway analysis, combining GWAS summary statistics on SCZ and lithium treatment response. Setting: International multicenter GWAS.Participants: Patients with BPD who had undergone lithium treatment were genotyped and retrospectively assessed for long-term treatment response (n=2,586). Main outcome measures:Clinical treatment response to lithium was defined on both the categorical and continuous scales using the ALDA score. The effect measures include odds ratios (ORs) and the proportion of variance explained (R 2 ), and a significant association was determined at p<0.05. Results:The PGS for SCZ was inversely associated with lithium treatment response in the categorical outcome (p=8x10 -5 ), at PT <5x10 -2 . Patients with BPD who had low polygenic load for SCZ responded better to lithium, with ORs for lithium response ranging from 3.46All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi....

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“…A significantly higher frequency of the HLA-A3 antigen among patients who re lapsed on lithium prophylaxis has been re ported by Perris et al [1979b], who also observed that patients with the B18 antigen were all non-responders to treatment.…”

Section: Introductionmentioning

confidence: 86%

Cell Membrane Predictors of Response to Lithium Prophylaxis of Affective Disorders

Vecchio¹,

Farzati²,

Maj³

et al. 1981

Neuropsychobiology

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HLA antigens and RBC/plasma lithium ratio were studied in a sample of 49 patients, diagnosed as bipolar affective psychotics (n = 22), unipolar depressive psychotics (n = 18) and cycloid psychotics (n = 9), receiving prophylactic lithium for 1–4 years and maintained at lithium plasma levels of 0.6–1.2 mEq/1. Mean values of the ratio were found to be significantly higher in patients who responded to treatment when compared with non-responders, whereas the frequency of the HLA-A3 antigen was significantly higher in non-responders. The only 6 patients with a lithium ratio above the median and the absence of the HLA-A3 antigen coexistent with bipolarity and a family history of the illness were all good responders to treatment. Further research in this field will probably bring about the isolation of a subgroup of lithium-responsive patients with well-defined clinical and biological features. When patients were divided into two subgroups according to their lithium ratios (above and below the median), the HLA-A3 and Aw26 antigens were found to be significantly more frequent in those with ratios below the median. It can be hypothesized that these antigens disturb lithium transport in some way, leading to low lithium ratio values.

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HL-A Antigens and the Response to Prophylactic Lithium

Cited by 35 publications

References 13 publications

Biological predictors of lithium response in bipolar disorder

Biological predictors of lithium response in bipolar disorder

High genetic loading of schizophrenia predicts poor response to lithium in patients with bipolar disorder: A polygenic score and cross-trait genetic analysis

Cell Membrane Predictors of Response to Lithium Prophylaxis of Affective Disorders

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