Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients
© 2023. The Author(s)..
RATIONALE: In bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment.
OBJECTIVES: We hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes.
RESULTS: We genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers.
CONCLUSIONS: Our study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium's immunomodulatory potential.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:241 |
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| Enthalten in: |
Psychopharmacology - 241(2024), 4 vom: 30. März, Seite 727-738 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sakrajda, Kosma [VerfasserIn] |
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| Links: |
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| Themen: |
130068-27-8 |
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| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00213-023-06505-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM365277835 |
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| 245 | 1 | 0 | |a Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 14.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a RATIONALE: In bipolar disorder (BD), immunological factors play a role in the pathogenesis and treatment of the illness. Studies showed the potential link between Abelson Helper Integration Site 1 (AHI1) protein, behavioural changes and innate immunity regulation. An immunomodulatory effect was suggested for lithium, a mood stabilizer used in BD treatment | ||
| 520 | |a OBJECTIVES: We hypothesized that AHI1 may be an important mediator of lithium treatment response. Our study aimed to investigate whether the AHI1 haplotypes and expression associates with lithium treatment response in BD patients. We also examined whether AHI1 expression and lithium treatment correlate with innate inflammatory response genes | ||
| 520 | |a RESULTS: We genotyped seven AHI1 single nucleotide polymorphisms in 97 euthymic BD patients and found that TG haplotype (rs7739635, rs9494332) was significantly associated with lithium response. We also showed significantly increased AHI1 expression in the blood of lithium responders compared to non-responders and BD patients compared to healthy controls (HC). We analyzed the expression of genes involved in the innate immune response and inflammatory response regulation (TLR4, CASP4, CASP5, NLRP3, IL1A, IL1B, IL6, IL10, IL18) in 21 lithium-treated BD patients, 20 BD patients treated with other mood stabilizer and 19 HC. We found significantly altered expression between BD patients and HC, but not between BD patients treated with different mood stabilizers | ||
| 520 | |a CONCLUSIONS: Our study suggests the involvement of AHI1 in the lithium mode of action. Moreover, mood-stabilizing treatment associated with the innate immunity-related gene expression in BD patients and only the lithium-treated BD patients showed significantly elevated expression of anti-inflammatory IL10, suggesting lithium's immunomodulatory potential | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Abelson Helper Integration Site 1 (AHI1) | |
| 650 | 4 | |a Bipolar disorder | |
| 650 | 4 | |a Immunomodulation | |
| 650 | 4 | |a Lithium | |
| 650 | 7 | |a Lithium |2 NLM | |
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| 650 | 7 | |a Interleukin-10 |2 NLM | |
| 650 | 7 | |a 130068-27-8 |2 NLM | |
| 650 | 7 | |a Antimanic Agents |2 NLM | |
| 650 | 7 | |a Lithium Compounds |2 NLM | |
| 700 | 1 | |a Bilska, Karolina |e verfasserin |4 aut | |
| 700 | 1 | |a Czerski, Piotr M |e verfasserin |4 aut | |
| 700 | 1 | |a Narożna, Beata |e verfasserin |4 aut | |
| 700 | 1 | |a Dmitrzak-Węglarz, Monika |e verfasserin |4 aut | |
| 700 | 1 | |a Heilmann-Heimbach, Stefanie |e verfasserin |4 aut | |
| 700 | 1 | |a Brockschmidt, Felix F |e verfasserin |4 aut | |
| 700 | 1 | |a Herms, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Nöthen, Markus M |e verfasserin |4 aut | |
| 700 | 1 | |a Cichon, Sven |e verfasserin |4 aut | |
| 700 | 1 | |a Więckowska, Barbara |e verfasserin |4 aut | |
| 700 | 1 | |a Rybakowski, Janusz K |e verfasserin |4 aut | |
| 700 | 1 | |a Pawlak, Joanna |e verfasserin |4 aut | |
| 700 | 1 | |a Szczepankiewicz, Aleksandra |e verfasserin |4 aut | |
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