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Interferon-induced depression

Kayoko Matsunami, Nao Nishida, Naoko Kaneko, Kazuho Ikeo, Licht Toyo-Oka, Hiroshi Takeuchi, Kentaro Matsuura, Akihiro Tamori, Hideyuki Nomura, Hitoshi Yoshiji, Masatoshi Imamura, Naohiko Masaki, Tatsuro Hayakawa, Tatsuya Ide, Noritomo Shimada, Fusao Ikeda, Keisuke Hino, Shuhei Nishiguchi, Chiaki Okuse, Shunsuke Nojiri, Kazunobu Sawamoto, Katsushi Tokunaga, Takashi Joh, Yasuhito Tanaka
The therapeutic use of interferon (IFN) is known to cause depression that frequently interrupts treatment. To identify genetic variants associated with IFN-induced depression, we conducted a genome-wide association study (GWAS) of 224 Japanese chronic hepatitis C patients receiving IFN-based therapy in a multicenter prospective study and stratified them into two groups according to the Beck Depression Inventory, Second Edition (BDI-II) score. In the GWAS stage, we selected 42 candidate single nucleotide polymorphisms (SNPs) to perform replication analysis in an independent set of 160 subjects...
2016: PloS One
Pei Wu, Wei-Dan Jiang, Jun Jiang, Juan Zhao, Yang Liu, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
This study investigated the effects of choline on intestinal mucosal immune and the possible mechanisms in fish by feeding juvenile Jian carp (Cyprinus carpio var. Jian) with graded levels of dietary choline (165-1820 mg/kg diet) for 65 days. The results firstly showed that choline deficiency induced inflammatory infiltration in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) of fish. Meanwhile, compared with the optimal choline group, choline deficiency decreased the activities of lysozyme and acid phosphatase, contents of complement 3 and IgM in the intestine, downregulated the mRNA levels of antimicrobial peptides (liver-expressed antimicrobial peptide (LEAP) 2A and defensin-3 in the PI and MI, LEAP-2B and hepcidin in the PI, MI and DI), anti-inflammatory cytokines (interleukin (IL) 10 and transforming growth factor β2 in the PI, MI and DI), and signaling molecule IκB in the PI, MI and DI; while upregulated the mRNA levels of pro-inflammatory cytokines (IL-6a and tumor necrosis factor α in the MI and DI, interferon γ2b in the PI and MI, IL-1β and IL-6b in the PI, MI and DI), and signaling molecules (Toll-like receptor 4 in the MI, myeloid differentiation primary response 88 in the PI and MI, Janus kinase 3 and tyrosine kinase 2 in the MI and DI, nuclear factor kappa B (NF-κB), signal transducers and activators of transcription (STAT) 4 and STAT5 in the PI, MI and DI) of juvenile Jian carp, further indicating that choline deficiency caused inflammation and immunity depression in the intestine of fish...
September 28, 2016: Fish & Shellfish Immunology
Hui-Jun Xu, Wei-Dan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou
This study explored the effects of vitamin C on the physical barriers and immune barriers, and relative mRNA levels of signaling molecules in the gill of grass carp (Ctenopharyngodon idella) under infection of Flavobacterium columnare. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) (1) increased reactive oxygen species, malondialdehyde and protein carbonyl (PC) contents (P < 0.05), decreased the copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and mRNA levels (P < 0...
September 15, 2016: Fish & Shellfish Immunology
Shailendra Bhatt, Pundarikakshudu Kilambi, Paresh Patel, Nirav Patel, Ashish Panchal, Gaurang Shah, Sunita Goswami
Accumulating data advocates that inflammatory mediators may contribute to depression in experimental models as well as in humans. Nonetheless, whether anti-inflammatory treatments can prevent depression still remains controversial. To substantiate our hypothesis, we used interferon - α- 2b model of depression using Sprague Dawley rats. Interferon - α- 2b is a cytokine which activates immune response and also produces depression. The animals were treated for 21 days with aspirin (10 mg/kg, po) dexamethasone (1mg/kg po) and amitriptyline (10 mg/kg po)...
August 25, 2016: Clinical and Experimental Pharmacology & Physiology
Proteesh Rana, Amit K Sharma, Smita Jain, Pravin Deshmukh, S K Bhattacharya, B D Banerjee, Pramod K Mediratta
BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness...
August 5, 2016: Journal of Basic and Clinical Physiology and Pharmacology
Yu-Min Lin, Bu-Chin Yu, Wen-Tai Chiu, Hung-Yu Sun, Yu-Chieh Chien, Hui-Chen Su, Shu-Yang Yen, Hsin-Wen Lai, Chyi-Huey Bai, Kung-Chia Young, Chiung-Wen Tsao
Fluoxetine, a well-known anti-depression agent, may act as a chemosensitizer to assist and promote cancer therapy. However, how fluoxetine regulates cellular signaling to enhance cellular responses against tumor cell growth remains unclear. In the present study, addition of fluoxetine promoted growth inhibition of interferon-alpha (IFN-α) in human bladder carcinoma cells but not in normal uroepithelial cells through lessening the IFN-α-induced apoptosis but switching to cause G1 arrest, and maintaining the IFN-α-mediated reduction in G2/M phase...
October 2016: International Journal of Oncology
Nadia Howard Tripp, Jessica Tarn, Andini Natasari, Colin Gillespie, Sheryl Mitchell, Katie L Hackett, Simon J Bowman, Elizabeth Price, Colin T Pease, Paul Emery, Peter Lanyon, John Hunter, Monica Gupta, Michele Bombardieri, Nurhan Sutcliffe, Costantino Pitzalis, John McLaren, Annie Cooper, Marian Regan, Ian Giles, David A Isenberg, Vadivelu Saravanan, David Coady, Bhaskar Dasgupta, Neil McHugh, Steven Young-Min, Robert Moots, Nagui Gendi, Mohammed Akil, Bridget Griffiths, Dennis W Lendrem, Wan-Fai Ng
OBJECTIVES: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS). METHODS: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance...
2016: RMD Open
Kohei Kawase, Kenji Kondo, Takeo Saito, Ayu Shimasaki, Atsushi Takahashi, Yoichiro Kamatani, Naoto Kawabe, Senju Hashimoto, Masashi Ikeda, Michiaki Kubo, Kentaro Yoshioka, Nakao Iwata
AIM: Pegylated interferon (PegIFN) therapies for hepatitis C virus (HCV) infection often induce a depressive state. This study aimed to identify the risk factors for and clinical characteristics of PegIFN-induced depressive state. METHODS: Sixty-nine subjects with HCV who received PegIFN therapy were enrolled. Before beginning therapy, all subjects were evaluated using the Neuroticism-Extraversion-Openness Five-Factor Inventory and the List of Threatening Events Questionnaire...
July 29, 2016: Psychiatry and Clinical Neurosciences
Nilay Hepgul, Carmine M Pariante, Sara Baraldi, Alessandra Borsini, Chiara Bufalino, Alice Russell, Kosh Agarwal, Anthony J Cleare, Daniel M Forton, Max Henderson, Valeria Mondelli, Gopinath Ranjith, Matthew Hotopf
Development of psychiatric symptoms during interferon-alpha therapy may be influenced by psychological factors. We examined illness perceptions using the Revised Illness Perceptions Questionnaire in 55 patients with chronic hepatitis C virus infection, due to receive interferon-alpha. The Hospital Anxiety and Depression Scale was used to assess the development of symptoms. Negative identity, consequences and emotional representation beliefs were significantly associated with both higher depression and anxiety scores...
July 24, 2016: Journal of Health Psychology
Yuki Murakami, Takaaki Ishibashi, Eiichi Tomita, Yukio Imamura, Tomoyuki Tashiro, Kanitta Watcharanurak, Makiya Nishikawa, Yuki Takahashi, Yoshinobu Takakura, Satoko Mitani, Hidetsugu Fujigaki, Yoshiji Ohta, Hisako Kubo, Takayoshi Mamiya, Toshitaka Nabeshima, Hyoung-Chun Kim, Yasuko Yamamoto, Kuniaki Saito
Depression is known to occur frequently in chronic hepatitis C viral (HCV) patients receiving interferon (IFN)-α therapy. In this study, we investigated whether indoleamine 2,3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy. Increases in serum kynurenine (KYN) and 3-hydroxykynurenine (3-HK) concentrations and in the ratios of KYN/TRP and 3-HK/kynurenic acid (KA) were much larger in depressive HCV patients than in non-depressed patients following therapy...
2016: Scientific Reports
Paolo Cassano, Eric Bui, Andrew H Rogers, Zandra E Walton, Rachel Ross, Mary Zeng, Mireya Nadal-Vicens, David Mischoulon, Amanda W Baker, Aparna Keshaviah, John Worthington, Elizabeth A Hoge, Jonathan Alpert, Maurizio Fava, Kwok K Wong, Naomi M Simon
INTRODUCTION: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. METHODS: Subjects aged 18-70 years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls (n = 236), were evaluated by trained raters and provided blood for cytokine measurements...
June 16, 2016: Australian and New Zealand Journal of Psychiatry
Yi Ren, Min Ye, Shengdi Chen, Jianqing Ding
BACKGROUND As the second most common neurodegenerative disorder after Alzheimer's disease (AD), Parkinson's disease (PD) principally impacts the motor system in approximately 7 million patients worldwide. The present study aimed to explore the effects of cluster of differentiation (CD200) on adenosine triphosphate-sensitive potassium (KATP) channels and inflammatory response in PD mice. MATERIAL AND METHODS We created an in vivo PD model by intraperitoneal injection of 30 mg/kg/day 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride (MPTP...
2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Yi Huang, Meihua Yang, Huajian Hu, Xiaodong Zhao, Liming Bao, Daochao Huang, Lihua Song, Yang Li
Aberrant STAT3 activation occurs in most human gastric cancers (GCs) and contributes to the malignant progression of GC, but mechanism(s) underlying aberrant STAT3 remain largely unknown. Here we demonstrated that the gene associated with retinoid interferon-induced mortality 19 (GRIM-19) was severely depressed or lost in GC and chronic atrophic gastritis (CAG) tissues and its loss contributed to GC tumorigenesis partly by activating STAT3 signaling. In primary human GC tissues, GRIM-19 was frequently depressed or lost and this loss correlated with advanced clinical stage, lymph node metastasis, H...
May 4, 2016: Oncotarget
Alexandra K Brooks, Marcus A Lawson, Robin A Smith, Tiffany M Janda, Keith W Kelley, Robert H McCusker
BACKGROUND: Increased tryptophan metabolism towards the production of kynurenine via indoleamine/tryptophan-2,3-dioxygenases (DOs: Ido1, Ido2, and Tdo2) is strongly associated with the prevalence of major depressive disorder in patients and the induction of depression-like behaviors in animal models. Several studies have suggested that activation of the immune system or elevated corticosteroids drive DO expression; however, mechanisms linking cytokines, corticosteroids, and DOs to psychiatric diseases remain unclear...
2016: Journal of Neuroinflammation
Atsuko Ohguchi, Hirofumi Yamauchi, Kunio Doi, Hiroyuki Nakayama
The present study was carried out to clarify the mechanisms of EMC virus-induced sialodacryoadenitis in mice during the acute phase infection focusing on the activation of type I interferon (IFN) signaling in the parotid and exorbital lachrymal glands. In the parotid gland, a few apoptotic acinar cells were detected at 2days post inoculation (DPI). The ratio of apoptotic acinar cells increased at 3 and 4DPI. On the other hand, in the exorbital lachrymal gland, apoptosis of acinar cells and infiltration of inflammatory cells mainly composed of mononuclear cells started at 3DPI, and prominent acinar cell damage developed at 4DPI...
June 2016: Experimental and Molecular Pathology
Nilay Hepgul, Annamaria Cattaneo, Kosh Agarwal, Sara Baraldi, Alessandra Borsini, Chiara Bufalino, Daniel M Forton, Valeria Mondelli, Naghmeh Nikkheslat, Nicola Lopizzo, Marco A Riva, Alice Russell, Matthew Hotopf, Carmine M Pariante
Owing to the unique opportunity to assess individuals before and after they develop depression within a short timeframe, interferon-α (IFN-α) treatment for chronic hepatitis C virus (HCV) infection is an ideal model to identify molecular mechanisms relevant to major depression, especially in the context of enhanced inflammation. Fifty-eight patients were assessed prospectively, at baseline and monthly over 24 weeks of IFN-α treatment. New-onset cases of depression were determined using the Mini International Neuropsychiatric Interview (MINI)...
September 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Bruno C Fábregas, Érica L M Vieira, Alexandre S Moura, Ricardo A Carmo, Renata E Ávila, Mery N S Abreu, Allan R Prossin, Antônio L Teixeira
OBJECTIVE: Major depression (MD) is a condition associated with both hepatitis C virus (HCV) infection and pegylated interferon (IFN)-α treatment. IFN induces a depressive syndrome that is associated with an inflammatory profile. We aimed to investigate whether there is any specific alteration in plasma biomarkers associated with MD. METHODS: HCV-monoinfected patients, with and without IFN treatment, were followed up for 18 months and went through structured psychiatric evaluation...
2016: Neuroimmunomodulation
Else Eising, Reinald Shyti, Peter A C 't Hoen, Lisanne S Vijfhuizen, Sjoerd M H Huisman, Ludo A M Broos, Ahmed Mahfouz, Marcel J T Reinders, Michel D Ferrari, Else A Tolner, Boukje de Vries, Arn M J M van den Maagdenberg
Familial hemiplegic migraine type 1 (FHM1) is a rare monogenic subtype of migraine with aura caused by mutations in CACNA1A that encodes the α1A subunit of voltage-gated CaV2.1 calcium channels. Transgenic knock-in mice that carry the human FHM1 R192Q missense mutation ('FHM1 R192Q mice') exhibit an increased susceptibility to cortical spreading depression (CSD), the mechanism underlying migraine aura. Here, we analysed gene expression profiles from isolated cortical tissue of FHM1 R192Q mice 24 h after experimentally induced CSD in order to identify molecular pathways affected by CSD...
March 31, 2016: Molecular Neurobiology
Jiqiang Guo, Wen Zhang, Lili Zhang, Huaxia Ding, Jingjing Zhang, Chen Song, Yanfei Zhang, Namei Xia, Mingfang Li, Yinming Liang, Xianzhang Hu, Haojiang Luan, Hui Wang
Depression is one of the major side effects of interferon alpha (IFN-α) treatment, but the molecular mechanism underlying IFN-α-induced depression remains unclear. Several studies have shown that the serotonin receptors 5-HTR1b and 5-HTR4 play key roles in the anti-depression effects associated with p11 (S100A10). We investigated the effects of IFN-α on the regulation of p11, 5-HTR1b and 5-HTR4 in mice and human neuroblastoma cells (SH-sy5y). We found that intraperitoneal injection with IFN-α in Balb/c mice resulted in an increased immobility in FST and TST, and potently lowered the protein levels of p11, 5-HTR1b and 5-HTR4 in the hippocampus or cingulate gyrus...
2016: Scientific Reports
Daniel Kim, Laura D Kubzansky, Andrea Baccarelli, David Sparrow, Avron Spiro, Letizia Tarantini, Laura Cantone, Pantel Vokonas, Joel Schwartz
OBJECTIVES: Although psychological factors have been associated with chronic diseases such as coronary heart disease (CHD), the underlying pathways for these associations have yet to be elucidated. DNA methylation has been posited as a mechanism linking psychological factors to CHD risk. In a cohort of community-dwelling elderly men, we explored the associations between positive and negative psychological factors with DNA methylation in promoter regions of multiple genes involved in immune/inflammatory processes related to atherosclerosis...
2016: BMJ Open
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