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      The Association between Suicide Attempts and Toxoplasma gondii Infection

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          Abstract

          Objective

          Chronic ‘latent’ infection by Toxoplasma gondii is common and most of the hosts have minimal symptoms or they are even asymptomatic. However, there are possible mechanisms by which T. gondii may affect human behavior and it may also cause humans to attempt suicide. This article aimed to investigate the potential pathophysiological relationship between suicide attempts and T. gondii infection in Korea.

          Methods

          One hundred fifty-five psychiatric patients with a history of suicide attempt and 135 healthy control individuals were examined with enzyme-linked immunoassays and fluorescent antibody technique for T. gondii seropositivity and antibody titers. The group of suicide attempters was interviewed regarding the history of suicide attempt during lifetime and evaluated using 17-item Korean version of Hamilton Depression Scale (HAMD), Columbia Suicide Severity Rating Scale (C-SSRS), State-Trait Anxiety Inventory (STAI) and Korean-Barratt Impulsiveness Scale (BIS).

          Results

          Immunoglobulin G antibodies were found in 21 of the 155 suicide attempters and in 8 of the 135 controls ( p=0.011). The Toxoplasma-seropositive suicide attempters had a higher HAMD score on the depressed mood and feeling of guilt subscales and a higher total score than the seronegative suicide attempters. T. gondii seropositive status was associated with higher C-SSRS in the severity and lethality subscales. T. gondii IgG seropositivity was significantly associated with higher STAI-X1 scores in the suicide attempters group.

          Conclusion

          Suicide attempters showed higher seroprevalence of T. gondii than healthy controls. Among the suicide attempters, the T. gondii seropositive and seronegative groups showed several differences in the aspects of suicide. These results suggested a significant association between T. gondii infection and psychiatric problems in suicidality.

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          Most cited references26

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          Cytokine-induced sickness behavior

          The behavioral repertoire of humans and animals changes dramatically following infection. Sick individuals have little motivation to eat, are listless, complain of fatigue and malaise, loose interest in social activities and have significant changes in sleep patterns. They display an inability to experience pleasure, have exaggerated responses to pain and fail to concentrate. Proinflammatory cytokines acting in the brain cause sickness behaviors. These nearly universal behavioral changes are a manifestation of a central motivational state that is designed to promote recovery. Exaggerated symptoms of sickness in cancer patients, such as cachexia, can be life-threatening. However, quality of life is often drastically impaired before the cancer becomes totally debilitating. Although basic studies in psychoneuroimmunology have defined proinflammatory cytokines as the central mediators of sickness behavior, a much better understanding of how cytokine and neurotransmitter receptors communicate with each other is needed. Advances that have been made during the past decade should now be extended to clinical studies in an attempt to alleviate sickness symptoms and improve quality of life for cancer patients.
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            Effects of Toxoplasma gondii infection on the brain.

            Toxoplasma gondii, an intracellular protozoan parasite, can infect humans in 3 different ways: ingestion of tissue cysts, ingestion of oocysts, or congenital infection with tachyzoites. After proliferation of tachyzoites in various organs during the acute stage, the parasite forms cysts preferentially in the brain and establishes a chronic infection, which is a balance between host immunity and the parasite's evasion of the immune response. A variety of brain cells, including astrocytes and neurons, can be infected. In vitro studies using non-brain cells have demonstrated profound effects of the infection on gene expression of host cells, including molecules that promote the immune response and those involved in signal transduction pathways, suggesting that similar effects could occur in infected brain cells. Interferon-gamma is the essential mediator of the immune response to control T. gondii in the brain and to maintain the latency of chronic infection. Infection also induces the production of a variety of cytokines by microglia, astrocytes, and neurons, which promote or suppress inflammatory responses. The strain (genotype) of T. gondii, genetic factors of the host, and probably the route of infection and the stage (tachyzoite, cyst, or oocyst) of the parasite initiating infection all contribute to the establishment of a balance between the host and the parasite and affect the outcome of the infection.
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              Tyrosine metabolism during interferon-alpha administration: association with fatigue and CSF dopamine concentrations.

              Chronic exposure to interferon (IFN)-alpha, an innate immune cytokine, produces high rates of behavioral disturbances, including depression and fatigue. These effects may be mediated by the actions of IFN-alpha on dopamine (DA) metabolism in the basal ganglia. Diminished conversion of phenylalanine (Phen) to tyrosine (Tyr), the primary amino acid precursor of DA, has been associated with inflammation, and may reflect decreased activity of the enzyme phenylalanine-hydroxylase (PAH). This study investigated the peripheral Phen/Tyr ratio in relation to cerebrospinal fluid (CSF) concentrations of DA and its metabolites in subjects treated with IFN-alpha plus ribavirin for hepatitis C and controls awaiting IFN-alpha therapy. Plasma Phen/Tyr ratios were significantly increased in IFN-alpha-treated subjects (n=25) compared to controls (n=9), and were negatively correlated with CSF DA (r=-0.59, df=15, p<0.05) and its metabolite, homovanillic acid (r=-0.67, df=15, p<0.01), and positively correlated with fatigue (r=0.44, df=23, p<.05) in IFN-alpha-treated patients but not controls. Given the role of tetrahydrobiopterin (BH4) in the PAH conversion of Phen to Tyr, CSF concentrations of BH4 and its inactive oxidized form, dihydrobiopterin (BH2), were examined along with CSF interleukin (IL)-6 in a subset of patients. BH2 concentrations were significantly increased in IFN-alpha-treated patients (n=12) compared to controls (n=7), and decreased CSF BH4 concentrations correlated with increased CSF IL-6 (r=-0.57, df=12, p<0.05). These results indicate that IFN-alpha is associated with decreased peripheral conversion of Phen to Tyr, which in turn is associated with reduced DA in the brain as well as fatigue. These alterations may be related to oxidation of BH4 secondary to IFN-alpha-induced activation of a CNS inflammatory response. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Clin Psychopharmacol Neurosci
                Clin Psychopharmacol Neurosci
                Clinical Psychopharmacology and Neuroscience
                Korean College of Neuropsychopharmacology
                1738-1088
                2093-4327
                February 2018
                28 February 2018
                : 16
                : 1
                : 95-102
                Affiliations
                [1 ]Department of Psychiatry, Soonchunhyang University College of Medicine, Cheonan, Korea
                [2 ]Korean Society of Infectious Diseases, Seoul, Korea
                [3 ]Department of Psychiatry, Soonchunhyang University College of Medicine, Seoul, Korea
                Author notes
                Address for correspondence: Se-Hoon Shim, MD, PhD, Department of Psychiatry, Soonchunhyang University Cheonan, Hospital, 31 Soonchunhyang 6-gil, Dongnam-gu, Cheonan, 31151, Korea, Tel: +82-41-570-2280, Fax: +82-41-570-3878, E-mail: shshim2k@ 123456daum.net
                Article
                cpn-16-095
                10.9758/cpn.2018.16.1.95
                5810447
                29397671
                0207b545-1f3d-4c32-9aed-c4c23d6c0845
                Copyright © 2018, Korean College of Neuropsychopharmacology

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 09 May 2017
                : 05 July 2017
                : 28 July 2017
                Categories
                Original Article

                suicide,toxoplasma,infection,depression,anxiety,impulsive bahavior

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