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      Evaluation of Serum Zonulin and Occludin Levels in Bipolar Disorder

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          Abstract

          Objective

          The etiology of bipolar disorder (BD) is still not fully understood. Little is currently known about the relationship between the interaction the gastrointestinal system and brain function and BD. Zonulin is the only known physiological modulator of tight junctions and is a biomarker for intestinal permeability (IP). Occludin is an integral transmembrane tight junction protein involved in the maintenance and assembly of such junctions. The current study aims to determine whether zonulin and occludin levels are altered in BD and whether they can serve as clinical biomarkers of disease.

          Methods

          Forty-four patients with BD and 44 healthy controls were included in this study. The Young Mania Rating Scale (YMRS) was used to determine the severity of manic symptoms, while the Hamilton Depression Rating Scale (HDRS) was used to determine the severity of depressive symptoms, and the Brief Functioning Rating Scale (FAST) to assess functionality. Venous blood samples were taken from all participants and serum zonulin and occludin levels were measured.

          Results

          The mean serum zonulin and occludin levels of the patients were significantly higher compared to the healthy control group. There was no difference between manic, depressive, and euthymic patients in terms of zonulin and occludin levels. There was no correlation between the total number of attacks, duration of disease, YMRS, HDRS, FAST scores, and zonulin and occludin levels in the patient group. The groups were divided into three according to body mass index as normal, overweight, and obese. Zonulin and occludin levels increased as body mass index increased and were highest in the obese group.

          Conclusion

          The study shows that zonulin and occludin levels in BD increase independently of the disease stage. Consideration of the role of IP in the pathogenesis of BD may be helpful in determining the appropriate treatment modality.

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          Most cited references48

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          A RATING SCALE FOR DEPRESSION

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            A rating scale for mania: reliability, validity and sensitivity

            An eleven item clinician-administered Mania Rating Scale (MRS) is introduced, and its reliability, validity and sensitivity are examined. There was a high correlation between the scores of two independent clinicians on both the total score (0.93) and the individual item scores (0.66 to 0.92). The MRS score correlated highly with an independent global rating, and with scores of two other mania rating scales administered concurrently. The score also correlated with the number of days of subsequent stay in hospital. It was able to differentiate statistically patients before and after two weeks of treatment and to distinguish levels of severity based on the global rating.
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              A meta-analysis of blood cytokine network alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder and depression

              Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P<0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P<0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P<0.01). The levels of IL-1β and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on cytokines were more robust for schizophrenia and MDD, but were more frequently studied than for acute mania. These findings have important implications for our understanding of the pathophysiology and treatment of major psychiatric disorders.
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                Author and article information

                Journal
                Psychiatry Investig
                Psychiatry Investig
                PI
                Psychiatry Investigation
                Korean Neuropsychiatric Association
                1738-3684
                1976-3026
                April 2023
                20 April 2023
                : 20
                : 4
                : 382-389
                Affiliations
                [1 ]Department of Psychiatry, University of Health Sciences, Erzurum Regional Training and Research Hospital, Erzurum, Türkiye
                [2 ]Department of Biochemistry, Ataturk University, Faculty of Medicine, Erzurum, Türkiye
                Author notes
                Correspondence: Sertaç Zengil, MD Department of Psychiatry, University of Health Sciences, Erzurum Regional Training and Research Hospital, Atatürk District, Çat Road Street, Number: 36, 25240 Yakutiye/Erzurum, Türkiye Tel: +90 (442) 4321000, Fax: +90 (442) 4321001 E-mail: sertaczengil@ 123456hotmail.com
                Author information
                http://orcid.org/0000-0001-9610-2869
                http://orcid.org/0000-0001-5189-3564
                Article
                pi-2022-0234
                10.30773/pi.2022.0234
                10151659
                37098666
                a25ece04-8f9c-4e94-8046-46ede1b628df
                Copyright © 2023 Korean Neuropsychiatric Association

                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
                : 16 August 2022
                : 21 November 2022
                : 12 February 2023
                Categories
                Original Article

                Clinical Psychology & Psychiatry
                bipolar disorder,blood-brain barrier,gastrointestinal tract,gastrointestinal microbiota,occludin,zonulin

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