Your browser doesn't support javascript.
loading
Differential inflammatory profiles in carriers of reciprocal 22q11.2 copy number variants.
O'Hora, Kathleen P; Amir, Carolyn M; Chiem, Emily; Schleifer, Charles H; Grigoryan, Vardui; Kushan-Wells, Leila; Chiang, Jessica J; Cole, Steven; Irwin, Michael R; Bearden, Carrie E.
Afiliação
  • O'Hora KP; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
  • Amir CM; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Chiem E; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Molecular, Cellular, and Integrative Physiology Program, University of California Los Angeles, Los Angeles, CA, USA.
  • Schleifer CH; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
  • Grigoryan V; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Kushan-Wells L; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA.
  • Chiang JJ; Department of Psychology, Georgetown University, DC, USA.
  • Cole S; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, U
  • Irwin MR; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Norman Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, U
  • Bearden CE; Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA; Department of Psychology, University of California, Los Angeles, CA, USA. Electronic address: cbearden@mednet.ucla.edu.
Psychoneuroendocrinology ; 169: 107135, 2024 Nov.
Article em En | MEDLINE | ID: mdl-39116521
ABSTRACT

BACKGROUND:

Genetic copy number variants (CNVs; i.e., a deletion or duplication) at the 22q11.2 locus confer increased risk of neuropsychiatric disorders and immune dysfunction. Inflammatory profiles of 22q11.2 CNV carriers can shed light on gene-immune relationships that may be related to neuropsychiatric symptoms. However, little is known about inflammation and its relationship to clinical phenotypes in 22q11.2 CNV carriers. Here, we investigate differences in peripheral inflammatory markers in 22q11.2 CNV carriers and explore their relationship with psychosis risk symptoms and sleep disturbance.

METHODS:

Blood samples and clinical assessments were collected from 22q11.2 deletion (22qDel) carriers (n=45), 22q11.2 duplication (22qDup) carriers (n=29), and typically developing (TD) control participants (n=92). Blood plasma levels of pro-inflammatory cytokines, including interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), and anti-inflammatory cytokine interleukin-10 (IL-10) were measured using a MesoScale Discovery multiplex immunoassay. Plasma levels of C-reactive protein (CRP) were measured using Enzyme-linked Immunosorbent Assay (ELISA). Linear mixed effects models controlling for age, sex, and body mass index were used to a) examine group differences in inflammatory markers between 22qDel, 22qDup, and TD controls, b) test differences in inflammatory markers between 22qDel carriers with psychosis risk symptoms (22qDelPS+) and those without (22qDelPS-), and c) conduct an exploratory analysis testing the effect of sleep disturbance on inflammation in 22qDel and 22qDup carriers. A false discovery rate correction was used to correct for multiple comparisons.

RESULTS:

22qDup carriers exhibited significantly elevated levels of IL-8 relative to TD controls (q<0.001) and marginally elevated IL-8 levels relative to 22qDel carriers (q=0.08). There were no other significant differences in inflammatory markers between the three groups (q>0.13). 22qDelPS+ exhibited increased levels of IL-8 relative to both 22qDelPS- (q=0.02) and TD controls (p=0.002). There were no relationships between sleep and inflammatory markers that survived FDR correction (q>0.14).

CONCLUSION:

Our results suggest that CNVs at the 22q11.2 locus may have differential effects on inflammatory processes related to IL-8, a key mediator of inflammation produced by macrophages and microglia. Further, these IL-8-mediated inflammatory processes may be related to psychosis risk symptoms in 22qDel carriers. Additional research is required to understand the mechanisms contributing to these differential levels of IL-8 between 22q11.2 CNV carriers and IL-8's association with psychosis risk.
Assuntos
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citocinas / Variações do Número de Cópias de DNA / Inflamação Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Psychoneuroendocrinology Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Citocinas / Variações do Número de Cópias de DNA / Inflamação Limite: Adolescent / Adult / Child / Female / Humans / Male Idioma: En Revista: Psychoneuroendocrinology Ano de publicação: 2024 Tipo de documento: Article