Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism?

Suchankova, Petra; Klang, Jonas; Cavanna, Carin; Holm, Göran; Nilsson, Staffan; Jönsson, Erik G.; Ekman, Agneta

doi:10.1503/jpn.110024

Cited by 20 publications

(21 citation statements)

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“…Elevated S100B levels correlate with paranoid [154] and negativistic psychosis [204], impaired cognition, poor therapeutic response and duration of illness [202]. Genetic polymorphisms in S100B [32] and receptor for advanced glycation end-product genes in schizophrenia cohorts (Table 2) [32,33,205] suggest these abnormalities are likely primary/pathogenic rather than secondary/biomarkers. Indeed, the decrease in serum S100B levels following treatment with antidepressants [201] and antipsychotics [196] suggests some clinical relevance of S100B to the pathophysiology of psychiatric disorders.…”

Section: Reviewmentioning

confidence: 99%

Neuroinflammation and psychiatric illness

Najjar

Pearlman

Alper

et al. 2013

J Neuroinflammation

601

473

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Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence supporting the pathogenic role of neuroinflammation in selected classical psychiatric disorders. Understanding how psychosocial, genetic, immunological and neurotransmitter systems interact can reveal pathogenic clues and help target new preventive and symptomatic therapies.

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Section: Reviewmentioning

confidence: 99%

Neuroinflammation and psychiatric illness

Najjar

Pearlman

Alper

et al. 2013

J Neuroinflammation

601

473

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“…Recent studies find that alcoholism is associated with increased brain microglial markers and expression of the proinflammatory cytokine CCL2 (MCP-1 [He and Crews 2008]) as well as increased TLR and HMGB1 expression (Crews et al 2013). In addition, increased expression of neuroimmune genes is associated with depression, neurodegeneration, and many other brain diseases (Forrest et al 2012; Garate et al 2013; Hanisch et al 2008; Maczurek et al 2008; Suchankova et al 2012). Signaling through RAGE can also contribute to neuroinflammation.…”

Section: Introductionmentioning

confidence: 99%

Increased receptor for advanced glycation end product expression in the human alcoholic prefrontal cortex is linked to adolescent drinking

Vetreno

Qin

Crews

2013

Neurobiology of Disease

119

162

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Adolescence is characterized behaviorally by increased impulsivity and risk-taking that declines in parallel with maturation of the prefrontal cortex and executive function. In the brain, the receptor for advanced glycation end products (RAGE) is critically involved in neurodevelopment and neuropathology. In humans, the risk of alcoholism is greatly increased in those who begin drinking between 13 and 15 years of age, and adolescents binge drink more than any other age group. We have previously found that alcoholism is associated with increased expression of neuroimmune genes. This manuscript tested the hypothesis that adolescent binge drinking upregulates RAGE and Toll-like receptor (TLR) 4 as well as their endogenous agonist, highmobility group box 1 (HMGB1). Immunohistochemistry, Western blot, and mRNA analyses found that RAGE expression was increased in the human post-mortem alcoholic orbitofrontal cortex (OFC). Further, an earlier age of drinking onset correlated with increased expression of RAGE, TLR4, and HMGB1. To determine if alcohol contributed to these changes, we used an adolescent binge ethanol model in rats (5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) and assessed neuroimmune gene expression. We found an age-associated decline of RAGE expression from late adolescence (P56) to young adulthood (P80). Adolescent intermittent ethanol exposure did not alter RAGE expression at P56, but increased RAGE in the young adult PFC (P80). Adolescent intermittent ethanol exposure also increased TLR4 and HMGB1 expression at P56 that persisted into young adulthood (P80). Assessment of young adult frontal cortex mRNA (RT-PCR) found increased expression of proinflammatory cytokines, oxidases, and neuroimmune agonists at P80, 25 days after ethanol treatment. Together, these human and animal data support the hypothesis that an early age of drinking onset upregulates RAGE/TLR4-HMGB1 and other neuroimmune genes that persist into young adulthood and could contribute to risk of alcoholism or other brain diseases associated with neuroinflammation.

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“…We point to Eysenck's concept of psychoticism, which links psychopathy to a tendency to become psychotic (Eysenck and Eysenck, 1977; Corr, 2010). Genetic studies have even identified potential genes linking psychoticism to schizophrenia (Suchankova et al, 2012). In the aforementioned memoire study, psychoticism was a ubiquitous finding in husbands and parents with high PCL-R scores.…”

Section: Is Psychopathy a Mental Disorder?mentioning

confidence: 99%