Elevated Maternal Interleukin-8 Levels and Risk of Schizophrenia in Adult Offspring

Brown, Alan S.; Hooton, J. W. L.; Schaefer, Catherine; Zhang, Haiying; Petkova, Eva; Babulas, Vicki P.; Perrin, Mary; Gorman, Jack M.; Süsser, Ezra

doi:10.1176/appi.ajp.161.5.889

Cited by 425 publications

(315 citation statements)

References 43 publications

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“…There is strong evidence that disruption of normal cytokine levels has a significant role as a risk factor for several neurodevelopmental defects, including schizophrenia and autism (Boulanger and Shatz, 2004;Brown et al, 2004b;Deverman and Patterson, 2009;Hsiao et al, 2013;Ponzio et al, 2007). Smith et al (2007) showed in 2007 that a single injection of the pro-inflammatory cytokine IL-6 to pregnant mice at embryonic day 12.5 lead to offspring deficits in prepulse inhibition (PPI) and latent inhibition (LI), both autism-relevant behaviors; these results were not seen following injection of the pro-inflammatory cytokines IL-1α, TNF-α, or IFN-γ.…”

Section: Cytokinesmentioning

confidence: 99%

“…Inflammation and immune signaling dysregulation can strongly influence neuropsychiatric behavior beyond just ASD (Haroon et al, 2012;Meyer and Feldon, 2009), with evidence pointing toward roles in bipolar disorder and PTSD (Jones and Thomsen, 2013), and perhaps most emphatically in schizophrenia (Brown et al, 2004b;Meyer and Feldon, 2009;Michel et al, 2012;Patterson, 2009). Schizophrenia and autism share many immune similarities, including a subset of patients with an etiology based in maternal infection and immune activation (Bauman et al, 2014;Boksa, 2010;Brown et al, 2004a;Meyer et al, 2005Meyer et al, , 2007Patterson, 2009;Urakubo et al, 2001).…”

Section: Asd As An Autoimmune Disordermentioning

confidence: 99%

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The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

367

293

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Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment.

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Section: Cytokinesmentioning

confidence: 99%

Section: Asd As An Autoimmune Disordermentioning

confidence: 99%

The Role of the Immune System in Autism Spectrum Disorder

Meltzer

Water

2016

Neuropsychopharmacol

367

293

View full text Add to dashboard Cite

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“…One prevalent hypothesis suggests that a common pathogenic mechanism involving increased production of cytokines and other mediators of inflammation mediates the link between prenatal infection and subsequent risk of schizophrenia. 8,9 Epidemiological support for this hypothesis, however, remains controversial, 10,11 suggesting furthermore that other mediating factors may play a role as well. 12 Exposure to traumatizing events during postnatal development is another environmental insult that has received broad recognition in the etiology of neurodevelopmental disorders.…”

Section: Introductionmentioning

confidence: 99%

Joint Effects of Exposure to Prenatal Infection and Peripubertal Psychological Trauma in Schizophrenia

Debost

Larsen

Munk‐Olsen

et al. 2016

Schizophrenia Bulletin

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Context: Prenatal infection and traumatizing experiences have both been linked with schizophrenia, but none of these factors seem sufficient to cause the disorder. However, recent evidence suggests that these environmental insults act in synergy to increase schizophrenia risk. Objective: To estimate the independent and joint effects of exposure to prenatal infection and peripubertal psychological trauma on the risk of schizophrenia. Design: Danish nationwide registers were linked in this prospective cohort study. We used survival analysis to report incidence rate ratios (IRRs) and corresponding 95% confidence intervals (95% CIs). Analyses were adjusted for age and calendar period and stratified by sex. Participants: A total of 979 701 persons born between 1980 and 1998 were followed up from January 1, 1995 through December 31, 2013, with 9656 having a hospital contact for schizophrenia. Results: Females exposed to prenatal infection had a significantly increased risk of schizophrenia (IRR: 1.61, 95% CI: 1.30-2.00), but not males (IRR: 0.99, 95% CI: 0.77-1.28). Peripubertal trauma was associated with increased risk in both sexes. Males, however, had a significantly higher risk of schizophrenia after exposure to both prenatal infection and peripubertal psychological trauma (IRR: 2.85, 95% CI: 2.32-3.51), with significant interaction between infection and peripubertal trauma on the multiplicative scale (P = .007). Conclusions: Our study demonstrated for the first time that prenatal infection and psychological trauma in peripubertal life can act in synergy to increase the risk of schizophrenia, with a potentially stronger susceptibility in males.

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“…13 Dysfunction of apoptosis may be involved in the pathophysiology of schizophrenia. 14 Abnormal activities of several interleukins, 15,16 including IL3, 17 have been observed in schizophrenia patients. All these lines of evidence suggest that IL3 is a plausible functional candidate for schizophrenia.…”

Section: Introductionmentioning

confidence: 99%