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Abelson Helper Integration Site 1 haplotypes and peripheral blood expression associates with lithium response and immunomodulation in bipolar patients.
Sakrajda, Kosma; Bilska, Karolina; Czerski, Piotr M; Narozna, Beata; Dmitrzak-Weglarz, Monika; Heilmann-Heimbach, Stefanie; Brockschmidt, Felix F; Herms, Stefan; Nöthen, Markus M; Cichon, Sven; Wieckowska, Barbara; Rybakowski, Janusz K; Pawlak, Joanna; Szczepankiewicz, Aleksandra.
Afiliación
  • Sakrajda K; Molecular and Cell Biology Unit, Poznan University of Medical Sciences, Poznan, Poland. ksakrajda@ump.edu.pl.
  • Bilska K; Doctoral School, Poznan University of Medical Sciences, Poznan, Poland. ksakrajda@ump.edu.pl.
  • Czerski PM; Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
  • Narozna B; Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
  • Dmitrzak-Weglarz M; Molecular and Cell Biology Unit, Poznan University of Medical Sciences, Poznan, Poland.
  • Heilmann-Heimbach S; Department of Psychiatric Genetics, Poznan University of Medical Sciences, Poznan, Poland.
  • Brockschmidt FF; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Herms S; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Nöthen MM; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Cichon S; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Wieckowska B; Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
  • Rybakowski JK; Institute of Human Genetics, University of Bonn, Bonn, Germany.
  • Pawlak J; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
  • Szczepankiewicz A; Department of Biomedicine, University Hospital Basel and University of Basel, Basel, Switzerland.
Psychopharmacology (Berl) ; 241(4): 727-738, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38036661
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Litio Límite: Humans Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Alemania
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trastorno Bipolar / Litio Límite: Humans Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Polonia Pais de publicación: Alemania