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Feresiadou, A., Nilsson, K., Ingelsson, M., Press, R., Kmezic, I., Nygren, I., . . . Burman, J. (2019). Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease. Journal of Neuroimmunology, 332, 31-36
Open this publication in new window or tab >>Measurement of sCD27 in the cerebrospinal fluid identifies patients with neuroinflammatory disease
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2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 332, p. 31-36Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Laboratory tests to assist in the diagnosis and monitoring of neuroinflammatory diseases are scarce. The soluble form of the CD27 molecule (sCD27) is shed in high concentrations by activated T cells and can be detected in the cerebrospinal fluid. The aim of this study was to investigate whether CSF quantitation of sCD27 could discriminate between inflammatory and non-inflammatory neurological diseases.

METHODS: The concentration of sCD27 was measured using a commercially available ELISA in 803 well-defined subjects from a study cohort comprised of 338 patients with neuroinflammatory disease, 338 with non-inflammatory neurological disease and 127 controls without neurological disease.

RESULTS: The median value of cerebrospinal fluid sCD27 was 64 pg/mL (IQR 0-200) in controls, 58 pg/mL (IQR 0-130) in patients with non-inflammatory disease and 740 pg/mL (IQR 230-1800) in patients with inflammatory disease. The likelihood ratio of having an inflammatory disease was 10 (sensitivity 74% and specificity 93%) if the sCD27 concentration was >250 pg/mL. In patients with a known inflammatory condition, the likelihood ratio of having an infection was 10 (sensitivity 40% and specificity 96%) if the sCD27 concentration was >2500 pg/mL.

CONCLUSIONS: The likelihood of having an inflammatory neurological condition is increased with elevated concentrations of sCD27 in cerebrospinal fluid. Rapid tests of sCD27 should be developed to assist clinicians in diagnosis of neuroinflammatory disease.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-381319 (URN)10.1016/j.jneuroim.2019.03.015 (DOI)000470940600004 ()30928869 (PubMedID)
Available from: 2019-04-26 Created: 2019-04-26 Last updated: 2019-07-05Bibliographically approved
Syk, M., Ellström, S., Mwinyi, J., Schiöth, H. B., Ekselius, L., Ramklint, M. & Cunningham, J. L. (2019). Plasma levels of leptin and adiponectin and depressive symptoms in young adults. Psychiatry Research, 272, 1-7
Open this publication in new window or tab >>Plasma levels of leptin and adiponectin and depressive symptoms in young adults
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2019 (English)In: Psychiatry Research, ISSN 0165-1781, E-ISSN 1872-7123, Vol. 272, p. 1-7Article in journal (Refereed) Published
Abstract [en]

Circulating levels of adipokines are known to be associated with depression. This study aimed to investigate a possible association between leptin, adiponectin and dimensional measures of depressive symptoms in young adults with and without psychiatric illness. Total plasma adiponectin and leptin levels were measured in 194 young adults seeking psychiatric ambulatory care and 57 healthy controls. Depressive symptoms were assessed using the Montgomery-Åsberg Depression Self-Rating Scale (MADRS-S). Analysis was performed on men and women separately. P-leptin levels were significantly elevated in patients compared with controls and correlated with total MADRS-S scores in the women. Women with P-leptin in the highest quartile reached a significantly higher MADRS-S score than women in the lowest quartile, but this difference disappeared after adjusting for body mass index (BMI) and antidepressant use. MADRS-S score was associated with P-leptin in female patients without antidepressant use, independently of BMI. There was no association between P-leptin levels and current major depression. P-adiponectin levels were not associated with depressive symptoms or current major depression. The findings indicate that P-leptin levels are associated with depressive symptom severity in young women; however, the association is linked to other factors, which challenges its usefulness as a biomarker for depression in clinical psychiatry.

Keywords
Adipokines, Depression, Inflammation, Mood disorders
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:uu:diva-376540 (URN)10.1016/j.psychres.2018.11.075 (DOI)000460994400001 ()30562581 (PubMedID)
Funder
Erik, Karin och Gösta Selanders FoundationFredrik och Ingrid Thurings StiftelseStiftelsen Söderström - Königska sjukhemmetThe Swedish Medical Association
Available from: 2019-02-06 Created: 2019-02-06 Last updated: 2019-04-10Bibliographically approved
Söderquist, F., Sundberg, I., Ramklint, M., Widerström, R., Hellström, P. M. & Cunningham, J. (2019). The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care. Psychosomatic Medicine, 81(1), 51-56
Open this publication in new window or tab >>The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care
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2019 (English)In: Psychosomatic Medicine, ISSN 0033-3174, E-ISSN 1534-7796, Vol. 81, no 1, p. 51-56Article in journal (Refereed) Published
Abstract [en]

Objective: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gutmotility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients.

Methods: Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale -IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11: 00 hours and 30 minutes after lunch) during the waking hours of 1 day.

Results: After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale -IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p =.015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association.

Conclusions: In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
depression, human, irritable bowel syndrome, melatonin, mental health
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-375232 (URN)10.1097/PSY.0000000000000644 (DOI)000455260000007 ()30299401 (PubMedID)
Funder
Erik, Karin och Gösta Selanders FoundationStiftelsen Söderström - Königska sjukhemmet
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved
Söderquist, F., Sundberg, I., Ramklint, M., Widerström, R., Hellström, P. M. & Cunningham, J. (2018). Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care. Paper presented at 73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY. Biological Psychiatry, 83(9), S185-S186
Open this publication in new window or tab >>Daytime Salivary Melatonin Related to Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care
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2018 (English)In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 83, no 9, p. S185-S186Article in journal, Meeting abstract (Other academic) Published
Keywords
Melatonin, Irritable Bowel Syndrome, Depression
National Category
Psychiatry Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-361431 (URN)000432466300462 ()
Conference
73rd Annual Scientific Convention and Meeting of the Society-of-Biological-Psychiatry (SOBP), 2018, New York, NY
Available from: 2018-12-10 Created: 2018-12-10 Last updated: 2018-12-12Bibliographically approved
Sundberg, I., Lannergård, A., Ramklint, M. & Cunningham, J. L. (2018). Direct-acting antiviral treatment in real world patients with hepatitis C not associated with psychiatric side effects: a prospective observational study. BMC Psychiatry, 18, Article ID 157.
Open this publication in new window or tab >>Direct-acting antiviral treatment in real world patients with hepatitis C not associated with psychiatric side effects: a prospective observational study
2018 (English)In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 18, article id 157Article in journal (Refereed) Published
Abstract [en]

Background: Treatment of Hepatitis C virus (HCV) infection has evolved from interferon (IFN)-based treatments to direct-acting antivirals (DAAs). Patients with HCV have an elevated psychiatric morbidity (including substance abuse) and patients with such comorbidity have often been excluded from treatment with IFN. To date, little is known about psychiatric adverse effects of DAA-based regimens. We therefore aimed to study the psychiatric side effects of new IFN-free treatment for HCV (including depressive symptoms and sleep) in real world patients also including those with a history of psychiatric diagnosis, substance abuse or drug dependence. Methods: Consecutive patients were monitored during treatment with three of the latest DAA agents (sofosbuvir, simeprevir and daclatasvir). Repeated expert psychiatric assessments from baseline to 12 weeks post-treatment were performed with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) clinical version and the self-report versions of the Montgomery Asberg Depression Rating Scale (MADRS-S) and the Pittsburgh Sleep Quality Index (PSQI). Friedman's test was performed to calculate differences in the MADRS-S and PSQI over time. In a post-hoc analysis Wilcoxon's test was used to compare baseline depressive symptoms with those at post-treatment. Spearman's rank correlation test was conducted in another post-hoc analysis to evaluate the correlation between symptoms of depression and HCV viral load at baseline. Results: At baseline, 15/17 patients (88%) had a history of any psychiatric diagnosis; 11 (65%) had a history of substance abuse or dependence; and 11 (65%) had previously been treated with IFN and six of those had experienced psychiatric side effects. There was no correlation between depressive symptoms and HCV viral load at baseline. Symptoms of depression did not increase during DAA treatment and were lower 12 weeks post-treatment compared with baseline: MADRS-S 10.7 vs. 8.3 (p = 0.01). This observation held when excluding patients taking antidepressant medication. Sleep quality did not significantly change during treatment. Adherence to treatment was estimated to 95% and sustained virological response was 88%. Conclusions: Despite high psychiatric morbidity, including previous substance abuse, patients successfully completed DAA treatment without increasing depressive symptoms or sleep disturbance. Symptoms of depression were significantly reduced 12 weeks after DAA treatment.

Keywords
Hepatitis C virus, Direct-acting antiviral, Depression, Sleep, Side effects
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-357557 (URN)10.1186/s12888-018-1735-6 (DOI)000433388700005 ()29843679 (PubMedID)
Funder
Swedish Society of MedicineFredrik och Ingrid Thurings StiftelseErik, Karin och Gösta Selanders Foundation
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2018-12-12Bibliographically approved
Bränn, E., Fransson, E., White, R. A., Papadopoulos, F. C., Edvinsson, Å., Kamali-Moghaddam, M., . . . Skalkidou, A. (2018). Inflammatory markers in women with postpartum depressive symptoms. Journal of Neuroscience Research
Open this publication in new window or tab >>Inflammatory markers in women with postpartum depressive symptoms
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2018 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547Article in journal (Refereed) Epub ahead of print
Abstract [en]

Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.

Keywords
cytokines, immune system, inflammation, maternal depression, pregnancy, protein markers
National Category
Psychiatry Immunology in the medical area Psychology
Identifiers
urn:nbn:se:uu:diva-362471 (URN)10.1002/jnr.24312 (DOI)30252150 (PubMedID)
Funder
Swedish Research Council, 521-2013-2339Swedish Research Council, 523-2014-2342Marianne and Marcus Wallenberg Foundation, 2011-Skalkidou
Available from: 2018-10-05 Created: 2018-10-05 Last updated: 2018-12-10Bibliographically approved
Just, D., Manberg, A., Lindholm Carlström, E., Cunningham, J. & Nilsson, P. (2018). TOWARDS MOLECULAR INSIGHTS INTO PSYCHIATRIC DISORDERS USING AFFINITY PROTEOMICS. Paper presented at 6th Biennial Conference of the Schizophrenia-International-Research-Society (SIRS), APR 04-08, 2018, Florence, ITALY. Schizophrenia Bulletin, 44, S223-S223
Open this publication in new window or tab >>TOWARDS MOLECULAR INSIGHTS INTO PSYCHIATRIC DISORDERS USING AFFINITY PROTEOMICS
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2018 (English)In: Schizophrenia Bulletin, ISSN 0586-7614, E-ISSN 1745-1701, Vol. 44, p. S223-S223Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-357174 (URN)000429541800539 ()
Conference
6th Biennial Conference of the Schizophrenia-International-Research-Society (SIRS), APR 04-08, 2018, Florence, ITALY
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically approved
Dumanski, J. P., Rasi, C., Björklund, P., Davies, H., Ali, A. S., Grönberg, M., . . . Tiensuu Janson, E. (2017). A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors. Endocrine-Related Cancer, 24(8), 427-443
Open this publication in new window or tab >>A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
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2017 (English)In: Endocrine-Related Cancer, ISSN 1351-0088, E-ISSN 1479-6821, Vol. 24, no 8, p. 427-443Article in journal (Refereed) Published
Abstract [en]

The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- > T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.

Keywords
DNA excision-repair pathway, cancer predisposition, familial cancer, oxidative stress, small intestinal carcinoid
National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-328686 (URN)10.1530/ERC-17-0196 (DOI)000406493000011 ()28634180 (PubMedID)
Available from: 2017-08-29 Created: 2017-08-29 Last updated: 2019-02-07Bibliographically approved
Syk, M., Ramklint, M., Fredriksson, R., Ekselius, L. & Cunningham, J. L. (2017). Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa. European psychiatry, 41, 30-36
Open this publication in new window or tab >>Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa
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2017 (English)In: European psychiatry, ISSN 0924-9338, E-ISSN 1778-3585, Vol. 41, p. 30-36Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN.

METHODS: The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls. Fifteen patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up 1-2years later, adipokines were reassessed in patients with BN and the Eating Disorder Examination Questionnaire was used to assess symptom severity.

RESULTS: P-adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (P<0.004 and <0.008 respectively). The difference remained significant after controlling for body mass index. P-adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ=0.72, P<0.04). P-leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (P<0.04) and P-leptin non-significantly lower.

CONCLUSIONS: Findings indicate a stable elevation of P-adiponectin in women with BN. P-adiponectin at follow-up correlates to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Adiponectin, Biomarker, Bulimia nervosa, Leptin, Prognosis
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-318532 (URN)10.1016/j.eurpsy.2016.09.006 (DOI)000397668400006 ()28049078 (PubMedID)
Funder
Swedish Society of Medicine
Available from: 2017-03-25 Created: 2017-03-25 Last updated: 2019-02-27Bibliographically approved
Cunningham, J., Zanzi, M., Willebrand, M., Ekselius, L. & Ramklint, M. (2017). Erratum to: No regrets. BMC Psychiatry, 17(1), Article ID 74.
Open this publication in new window or tab >>Erratum to: No regrets
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2017 (English)In: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 17, no 1, article id 74Article in journal (Refereed) Published
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-318109 (URN)10.1186/s12888-017-1228-z (DOI)28219362 (PubMedID)
Available from: 2019-02-06 Created: 2019-02-06 Last updated: 2019-07-18Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-7876-7779

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