Depression and anxiety in patients receiving interferon-alpha: The role of illness perceptions

Hepgul, Nilay; Pariante, Carmine M.; Baraldi, Sara Bonini; Borsini, Alessandra; Bufalino, Chiara; Russell, Ailsa; Agarwal, Kosh; Cleare, Anthony J.; Forton, Daniel; Henderson, M. Todd; Mondelli, Valeria; Ranjith, Gopinath; Hotopf, Matthew

doi:10.1177/1359105316658967

Cited by 14 publications

(12 citation statements)

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“…In contrast, the higher TW4 levels of IL-10 in PF subside by TW24 and are only present in the PF group, suggesting that the IFN-α-induced increase in this cytokine indicates a specific sensitivity to an immune stimulus in those who are also at risk of fatigue-like syndromes. It is also of note that we have recently published, in a different but overlapping sample of patients taking IFN-α, that the IFN-α-induced increase in IL-6 levels is not related to the development of IFN-α-induced depression (Hepgul et al, 2016a, 2016b). Thus, this indicates a specific role of IL-6 in the development of fatigue.…”

Section: Discussionmentioning

confidence: 89%

“…In addition to IFN-α/rib, eight subjects (14%) were also prescribed a direct-acting antiviral (‘triple therapy’, adding boceprevir, telaprevir or simeprevir), after treatment protocols changed across the UK. The sample is partially overlapping with that in the publication by Hepgul et al (2016a, 2016b) (of n = 55, overlap of n = 35), though post-treatment data was not presented in Hepgul et al’s paper. Exclusion criteria included any autoimmune disorders or causes of liver disease other than HCV, and co-infection with HIV or Hepatitis B.…”

Section: Methodsmentioning

confidence: 99%

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Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

Russell

Hepgul

Nikkheslat

et al. 2019

Psychoneuroendocrinology

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HighlightsBaseline fatigue is not associated with the development of persistent fatigue after IFN-α.IFN-α-induced persistent fatigue is associated with increased baseline IL-10.Patients who develop persistent fatigue experience greater increases in IL-6 and 10 in response to IFN-α.Persistently fatigued patients recover at a similar rate, but from a more severe acute response to the initial trigger.Once established, neither the persistent fatigue phenotype, nor CFS, are associated with peripheral immune activation.

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Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

Russell

Hepgul

Nikkheslat

et al. 2019

Psychoneuroendocrinology

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“…Overall, our findings help clarify the molecular mechanisms underpinning the detrimental effects of IFN-α on both neurogenesis and apoptosis, and these mechanisms have translational potential. It is well known that therapeutic use of IFN-α is associated with many neuropsychiatric side effects, including depression, anxiety, and cognitive abnormalities ( Raison et al, 2005 ; Hepgul et al, 2016a ). Interestingly, the aforementioned animal studies have shown a significant upregulation of STAT1, ISG15, and USP18 genes in the mouse brain, including the hippocampus ( Wang and Campbell, 2005 ; Wang et al, 2008 ), a brain region involved in neurogenesis-dependent cognitive functions, such as memory and attention, often impaired in patients with depression ( Moylan et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Initially identified for its anti-viral properties, interferon (IFN)-α is a pleiotropic molecule and a major mediator of innate and adaptive immune responses ( Pestka, 2000 ). In addition to its immuno-modulatory properties, IFN-α has been shown to have a number of effects on the brain, ranging from increased neurotoxicity ( Alboni et al, 2013 ) to the development of behavioral phenotypes, in both human and animal models ( Felger et al, 2007 ; Hepgul et al, 2016a ). In particular, IFN-α treatment has been shown to cause depressive symptoms as well as other neuropsychiatric adverse effects, such as anxiety, sleep disorders, and memory impairment, when administered to patients as a treatment for chronic viral hepatitis ( Raison et al, 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms

Borsini

Cattaneo

Malpighi

et al. 2017

International Journal of Neuropsychopharmacology

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BackgroundIn humans, interferon-α treatment for chronic viral hepatitis is a well-recognized clinical model for inflammation-induced depression, but the molecular mechanisms underlying these effects are not clear. Following peripheral administration in rodents, interferon-α induces signal transducer and activator of transcription-1 (STAT1) within the hippocampus and disrupts hippocampal neurogenesis.MethodsWe used the human hippocampal progenitor cell line HPC0A07/03C to evaluate the effects of 2 concentrations of interferon-α, similar to those observed in human serum during its therapeutic use (500 pg/mL and 5000 pg/mL), on neurogenesis and apoptosis.ResultsBoth concentrations of interferon-α decreased hippocampal neurogenesis, with the high concentration also increasing apoptosis. Moreover, interferon-α increased the expression of interferon-stimulated gene 15 (ISG15), ubiquitin-specific peptidase 18 (USP18), and interleukin-6 (IL-6) via activation of STAT1. Like interferon-α, co-treatment with a combination of ISG15, USP18, and IL-6 was able to reduce neurogenesis and enhance apoptosis via further downstream activation of STAT1. Further experiments showed that ISG15 and USP18 mediated the interferon-α-induced reduction in neurogenesis (potentially through upregulation of the ISGylation-related proteins UBA7, UBE2L6, and HERC5), while IL-6 mediated the interferon-α-induced increase in apoptosis (potentially through downregulation of aquaporin 4). Using transcriptomic analyses, we showed that interferon-α regulated pathways involved in oxidative stress and immune response (e.g., Nuclear Factor (erythroid-derived 2)-like 2 [Nrf2] and interferon regulatory factor [IRF] signaling pathway), neuronal formation (e.g., CAMP response element-binding protein [CREB] signaling), and cell death regulation (e.g., tumor protein(p)53 signaling).ConclusionsWe identify novel molecular mechanisms mediating the effects of interferon-α on the human hippocampus potentially involved in inflammation-induced neuropsychiatric symptoms.

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“…Sin embargo, se ha reconocido que estos pacientes pueden presentar una alta variabilidad en la respuesta emocional (Stanton, et al, 2007). Cabe anotar que estos síntomas podrían estar asociados con las percepciones de la enfermedad (Hepgul et al, 2016;Nowicka-Sauer et al, 2018;Vinaccia-Alpi, et al, 2017). Adicionalmente, existe evidencia de que los niveles más bajos de depresión se asocian con prácticas de cuidado más estables (Bennett, Gruszczynska & Marke, 2015; Shim, Lee & Min, 2018), y con la percepción del dolor (Hansdorfer-et al, 2016).…”

Section: Introductionunclassified

Percepciones de la enfermedad y hábitos de vida saludable en personas con enfermedades crónicas

et al. 2019

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Objetivo: Evaluar las percepciones de la enfermedad que se asocian con hábitos de vida saludable en pacientes con enfermedades crónicas en Medellín y municipios aledaños. Método: Estudio prospectivo correlacional basado en la aplicación del cuestionario breve de percepciones de la enfermedad (BIPQ), cuestionario de la salud del paciente (PHQ-9), cuestionario de ansiedad generalizada (GAD-7) y un cuestionario de hábitos de vida saludable. Participaron 51 pacientes con diferentes enfermedades crónicas: migraña, cáncer de seno, diabetes, artritis reumatoide, enfermedad cardiovascular e hipertensión arterial primaria. La evaluación de los hábitos de vida saludable se llevó a cabo tres meses después. Resultados: Se encontró que en promedio los participantes comprenden su enfermedad (M = 8,09, D.T. =2,48), perciben que sus acciones (M = 7,06, D.T. = 2,79) y el tratamiento (M = 7,89, D.T. = 2,69) la controlan y que esta tiene un carácter crónico (M = 7,49, D.T. = 3,16); que hay correlaciones entre los Hábitos de vida saludables (HVS) con la percepción de consecuencias de forma negativa, y la identidad y preocupación emocional de manera positiva (p < 0,05). Además, que una relación lineal entre las consecuencias (Beta= 0,391) y la preocupación emocional por la enfermedad (Beta = 0,311) con los HVS, F (5, 45) = 2,707, p < 0,05. Las proporciones de depresión y ansiedad en la muestra fueron similares a las de la población general. Conclusiones: La percepción de que una enfermedad tiene consecuencias negativas y la preocupación por esta lleva a la implementación de comportamientos saludables.

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Depression and anxiety in patients receiving interferon-alpha: The role of illness perceptions

Cited by 14 publications

References 50 publications

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

Persistent fatigue induced by interferon-alpha: a novel, inflammation-based, proxy model of chronic fatigue syndrome

Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms

Percepciones de la enfermedad y hábitos de vida saludable en personas con enfermedades crónicas

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