Interferon alpha (IFNα) and psychiatric syndromes

Schaefer, Martin; Engelbrecht, Marc A.; Gut, Oliver; Fiebich, Bernd L.; Bauer, Joachim; Schmidt, F.; Grunze, Heinz; Lieb, Klaus

doi:10.1016/s0278-5846(01)00324-4

Cited by 193 publications

(150 citation statements)

References 99 publications

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“…43 Despite intense studies and the development of various drug therapies, the etiopathogenesis for common human mental disorders such as affective disorders, anxiety and schizophrenia remains poorly understood. 44,45 However, recent clinical observations from patients on IFN-a therapy 10,11 and genetic studies on autoimmune mice 46 suggest a direct link between IFN-a and neuropsychiatric disorders. Therapeutic application of IFN-a presents a wide range of side effects, particularly CNS complications, including depression, anxiety and cognitive abnormalities often leading to the discontinuation of the therapy.…”

Section: Discussionmentioning

confidence: 99%

“…9 A direct connection between IFN-a and human CNS disorders came from recent clinical observations in which chronic, high-dose IFN-a therapy was frequently found to lead to severe neurotoxicity and neuropsychiatric complications such as agitation, depression, anxiety and memory loss in as high as 30-45% of patients. 10,11 Depression-and anxiety-like behaviors, associated with disturbances in monoamine neurotransmission 12 following systemic IFN-a treatment, have also been reported in rodents. 6,13 In search of the molecular basis for neuromodulatory actions, especially neuropsychiatric complications associated with systemic IFN-a, recent positron emission tomography and functional magnetic resonance imaging have recorded metabolic changes from patients undergoing IFN-a therapy in several parts of the brain.…”

Section: Introductionmentioning

confidence: 99%

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Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

2007

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The prime anti-viral cytokine interferon-a (IFN-a) has been implicated in several central nervous system (CNS) disorders in addition to its beneficial effects. Systemic IFN-a treatment causes severe neuropsychiatric complications in humans, including depression, anxiety and cognitive impairments. While numerous neuromodulatory effects by IFN-a have been described, it remains unresolved whether or not systemic IFN-a acts directly on the brain to execute its CNS actions. In the present study, we have analyzed the genes directly regulated in post-IFN-a receptor signaling and found that intraperitoneal administration of mouse IFN-a, but not human IFN-a, activated expression of several prototypic IFN-stimulated genes (ISGs), in particular signal transducers and activators of transcription (STAT1), IFN-induced 15 kDa protein (ISG15), ubiquitin-specific proteinase 18 (USP18) and guanylate-binding protein 3 (GBP3) in the brain. A similar temporal profile for the regulated expression of these IFN-aactivated ISG genes was observed in the brain compared with the peripheral organs. Dual labeling in situ hybridization combined with immunocytochemical staining demonstrated a wide distribution of the key IFN-regulated gene STAT1 transcripts in the different parenchyma cells of the brain, particularly neurons. The overall response to IFN-a challenge was abolished in STAT1 knockout mice. Together, our results indicate a direct, STAT1-dependent action of systemic IFN-a in the CNS, which may provide the basis for a mechanism in humans for neurological/neuropsychiatric illnesses associated with IFN-a therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

2007

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“…The adverse effects of interferons, which are clinically used for treatment of hepatitis, cirrhosis and cancer, included paranoid psychosis and depression. 45 Expression of ADAR1 is known to be induced by external stimuli including interferon from interferoninducible promoter. 46 High level of ADAR1 induced by interferon causes increased RNA editing at A, B and C sites, and decrease at D site, resulted in increase of the VSI isoform in the glioblastoma cell line.…”

Section: Effect Of Genetic Variations Of Htr2c On Expression and Rna mentioning

confidence: 99%

Serotonin receptor 2C and mental disorders: Genetic, expression, and RNA editing studies

Iwamoto¹,

Bundo²,

Kato³

2009

RNA Biology

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“…In our study, an apparently lower rate of neuropsychiatric-related AEs was also observed in CHB patients (P \ 0.0001 * P = 0.003). Neuropsychiatric events including suicide, depression, relapse of drug addiction, and aggressive behavior have been reported in patients with and without previous psychiatric disorders during Peg-IFN therapy [23]. The etiology of IFN-induced depression may derive, at least in part, from the antiserotonergic effects of IFN.…”

Section: Discussionmentioning

confidence: 99%

Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan

et al. 2010

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Purpose Pegylated interferon (Peg-IFN)-based therapy is effective in treating chronic hepatitis B (CHB) and C (CHC) but frequently induces adverse events (AEs). This study was conducted to compare the incidence of Peg-IFNbased therapy-associated AEs in Taiwanese patients with CHB and CHC. Methods Fifty-six patients with CHB and 103 age-, sexand treatment duration-matched patients with CHC were enrolled. Patients with CHB were treated with Peg-IFN-a2a 180 lg/week for 24 weeks (HBeAg ? , n = 31) or 48 weeks (HBeAg -, n = 25); patients with CHC were treated with Peg-IFN-a-2a 180 lg/week plus ribavirin 1,000-1,200 mg/day for 24 weeks (genotype 2/3, n = 57) or 48 weeks (genotype 1, n = 46).Results Significantly higher incidences of Peg-IFN-related AEs, especially neuropsychiatric symptoms, and ribavirin-associated skin manifestations were observed in patients with CHC compared with those with CHB, with either the 24-or 48-week regimen. Frequencies of laboratory abnormalities, except for anemia, were comparable in both groups. Neither group showed overt hepatic decompensation. Frequency of dose reduction was similar between the groups. Substantially higher rates of early termination and severe AEs were observed in patients with CHC. Conclusions Patients with CHB treated with Peg-IFN had fewer AEs than patients with CHC treated with Peg-IFN/ ribavirin. All patients were treated safely.

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Interferon alpha (IFNα) and psychiatric syndromes

Cited by 193 publications

References 99 publications

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

Systemic interferon-α regulates interferon-stimulated genes in the central nervous system

Serotonin receptor 2C and mental disorders: Genetic, expression, and RNA editing studies

Comparison of adverse effects related to pegylated interferon-based therapy for patients with chronic hepatitis B and chronic hepatitis C in Taiwan

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