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Sundberg, I., Jacobson, A., Ramklint, M., Just, D., Ekselius, L. & Cunningham, J. (2020). Daytime melatonin levels in saliva are associated with inflammatory markers and anxiety disorders. Psychoneuroendocrinology, 112, Article ID 104514.
Open this publication in new window or tab >>Daytime melatonin levels in saliva are associated with inflammatory markers and anxiety disorders
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2020 (English)In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 112, article id 104514Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The bidirectional interaction between melatonin and the immune system has largely gone unexplored in a clinical context and especially in a psychiatric population. This study explored the association between melatonin during the day and inflammatory cytokines in young adult patients seeking psychiatric care.

METHODS: Samples and data were collected from 108 young adults (mean age 21, SD = 2) at an outpatient clinic for affective disorders. Daytime saliva melatonin levels were analyzed with enzyme-linked immunosorbent assay (ELISA) in relation to normalized serum expression levels of 72 inflammatory markers in a proximity extension assay (PEA). In a post hoc analysis the markers associated with melatonin were tested in a generalized linear model to see whether there is a relationship to anxiety disorder or depression.

RESULTS: After Bonferroni correction for multiple testing, melatonin levels at 11:00 were positively correlated with CD5 (p = 4.2e-4). Melatonin levels after lunch were correlated with CCL2/MCP-1 (p = 4.2e-4), CCL3/MPI-1α (p = 6.5e-4) and VEGF-A (p = 5.3e-6). In the generalized linear model, positive associations were found for the presence of any anxiety disorder with melatonin after lunch (p = 0.046), VEGF-A (p = 0.001) and CCL3/MPI-1α (p = 0.001).

CONCLUSION: Daytime saliva levels of melatonin were related to several inflammatory markers in young adults with psychiatric disorders. This observation likely reflects the bidirectional relationship between melatonin production and the immune system. These findings may have relevance for the understanding of psychiatric disorders and other conditions associated with low-grade inflammation.

Keywords
Anxiety, Depression, Inflammation, Melatonin, Oxidative stress
National Category
Psychiatry
Research subject
Psychiatry
Identifiers
urn:nbn:se:uu:diva-369409 (URN)10.1016/j.psyneuen.2019.104514 (DOI)000509615800011 ()31776047 (PubMedID)
Funder
Swedish Research CouncilErik, Karin och Gösta Selanders FoundationFredrik och Ingrid Thurings StiftelseStiftelsen Söderström - Königska sjukhemmetSwedish Society of Medicine
Note

Authors and Title in Thesis List of papers:

I. Sundberg, A. Jacobson, M. Ramklint, L. Ekselius, and J. Cunningham “Daytime Melatonin Levels in Saliva are Associated with Inflammatory Markers and Anxiety Disorders in Young Adults with Psychiatric Disease”

Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2020-04-16Bibliographically approved
Nilsson, A., Orwelius, L., Sveen, J., Willebrand, M., Ekselius, L., Gerdin, B. & Sjoberg, F. (2019). Anxiety and depression after burn, not as bad as we think-A nationwide study. Burns, 45(6), 1367-1374
Open this publication in new window or tab >>Anxiety and depression after burn, not as bad as we think-A nationwide study
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2019 (English)In: Burns, ISSN 0305-4179, E-ISSN 1879-1409, Vol. 45, no 6, p. 1367-1374Article in journal (Refereed) Published
Abstract [en]

Objective: A history of psychiatric disorders is more common among patients who have had burns than in the general population. To try and find out the scale of the problem we have assessed self-reported symptoms of anxiety and depression after a burn. Methods: Consecutive patients with burns measuring more than 10% total body surface area or duration of stay in hospital of seven days or more were included. Personal and clinical details about the patients were extracted from the database at each center. Data were collected from the Hospital Anxiety and Depression Scale, as well as Health-Related Quality of Life (HRQoL; Short Form-36, SF-36) and questionnaires about socioeconomic factors. All results were obtained 12 and 24 months after the burn, and compared with those from a reference group. Results: A total of 156 patients responded to the questionnaires. Mean (SD) age and TBSA (%) were 46 (16.4) years and 23.6 (19.2) %, respectively. There were no differences in incidence between the burn and reference groups in anxiety or depression either 12 or 24 months after the burn. Those who reported higher anxiety and depression scores also had consistently poorer HRQoL as assessed by the SF-36. Conclusion: Seen as a group, people who have had burns report anxiety and depression the same range as a reference group. Some patients, however, express more anxiety and depression, and concomitantly poorer HRQoL. These patients should be identified, and offered additional support. (C) 2019 Elsevier Ltd and ISBI. All rights reserved.

Place, publisher, year, edition, pages
ELSEVIER SCI LTD, 2019
Keywords
Burns, Quality of life, Anxiety, Depression, Follow-up studies
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-394054 (URN)10.1016/j.burns.2019.03.014 (DOI)000483339500013 ()31378623 (PubMedID)
Available from: 2019-10-03 Created: 2019-10-03 Last updated: 2019-10-03Bibliographically approved
Axfors, C., Bränn, E., Henriksson, H. E., Hellgren, C., Kallak, T. K., Fransson, E., . . . Skalkidou, A. (2019). Cohort profile: the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort. BMJ Open, 9(10), Article ID e031514.
Open this publication in new window or tab >>Cohort profile: the Biology, Affect, Stress, Imaging and Cognition (BASIC) study on perinatal depression in a population-based Swedish cohort
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2019 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, no 10, article id e031514Article in journal (Refereed) Published
Abstract [en]

PURPOSE: With the population-based, prospective Biology, Affect, Stress, Imaging and Cognition (BASIC) cohort, we aim to investigate the biopsychosocial aetiological processes involved in perinatal depression (PND) and to pinpoint its predictors in order to improve early detection.

PARTICIPANTS: From September 2009 to November 2018, the BASIC study at Uppsala University Hospital, Sweden, has enrolled 5492 women, in 6478 pregnancies, of which 46.3% first-time pregnancies and with an average age of 31.5 years. After inclusion around gestational week 16-18, participants are followed-up with data collection points around gestational week 32, at childbirth, as well as three times postpartum: after 6 weeks, 6 months and 1 year. At the last follow-up, 70.8% still remain in the cohort.

FINDINGS TO DATE: In addition to internet-based surveys with self-report instruments, participants contribute with biological samples, for example, blood samples (maternal and from umbilical cord), biopsies (umbilical cord and placenta) and microbiota samples. A nested case-control subsample also takes part in cognitive and emotional tests, heart rate variability tests and bioimpedance tests. Subprojects have identified various correlates of PND of psychological and obstetric origin in addition to factors of the hypothalamic-pituitary-adrenal axis and immune system.

FUTURE PLANS: In parallel with the completion of data collection (final follow-up November 2019), BASIC study data are currently analysed in multiple subprojects. Since 2012, we are conducting an ongoing follow-up study on the participants and their children up to 6 years of age (U-BIRTH). Researchers interested in collaboration may contact Professor Alkistis Skalkidou (corresponding author) with their request to be considered by the BASIC study steering committee.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2019
Keywords
cohort study, mother-child relations, pituitary-adrenal system, postpartum depression, pregnancy, psychoneuroimmunology
National Category
Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:uu:diva-404667 (URN)10.1136/bmjopen-2019-031514 (DOI)31641004 (PubMedID)
Funder
Swedish Research Council, 523-2014-2342Swedish Research Council, 523-2014-07605Swedish Research Council, 521-2013-2339Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of TechnologyMarianne and Marcus Wallenberg FoundationStiftelsen Söderström - Königska sjukhemmetSwedish Society of MedicineForte, Swedish Research Council for Health, Working Life and WelfareFredrik och Ingrid Thurings Stiftelse
Available from: 2020-02-25 Created: 2020-02-25 Last updated: 2020-03-27Bibliographically approved
Bhandage, A. K., Cunningham, J. L., Jin, Z., Shen, Q., Bongiovanni, S., Korol, S., . . . Birnir, B. (2019). Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers. International Journal of Molecular Sciences, 20(24), Article ID 6172.
Open this publication in new window or tab >>Depression, GABA, and Age Correlate with Plasma Levels of Inflammatory Markers
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 24, article id 6172Article in journal (Refereed) Published
Abstract [en]

Immunomodulation is increasingly being recognised as a part of mental diseases. Here, we examined whether levels of immunological protein markers changed with depression, age, or the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). An analysis of plasma samples from patients with a major depressive episode and control blood donors (CBD) revealed the expression of 67 inflammatory markers. Thirteen of these markers displayed augmented levels in patients compared to CBD. Twenty-one markers correlated with the age of the patients, whereas 10 markers correlated with the age of CBD. Interestingly, CST5 and CDCP1 showed the strongest correlation with age in the patients and CBD, respectively. IL-18 was the only marker that correlated with the MADRS-S scores of the patients. Neuronal growth factors (NGFs) were significantly enhanced in plasma from the patients, as was the average plasma GABA concentration. GABA modulated the release of seven cytokines in anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) from the patients. The study reveals significant changes in the plasma composition of small molecules during depression and identifies potential peripheral biomarkers of the disease.

Place, publisher, year, edition, pages
MDPI, 2019
Keywords
GABAA receptor, inflammation, mental health
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-401785 (URN)10.3390/ijms20246172 (DOI)000506840100066 ()31817800 (PubMedID)
Funder
Swedish Research CouncilSwedish Society of Medicine
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-03-05Bibliographically approved
Hörberg, N., Kouros, I., Ekselius, L., Cunningham, J., Willebrand, M. & Ramklint, M. (2019). Early Trauma Inventory Self-Report Short Form (ETISR-SF): validation of the Swedish translation in clinical and non-clinical samples.. Nordic Journal of Psychiatry, 73(2), 81-89
Open this publication in new window or tab >>Early Trauma Inventory Self-Report Short Form (ETISR-SF): validation of the Swedish translation in clinical and non-clinical samples.
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2019 (English)In: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 73, no 2, p. 81-89Article in journal (Refereed) Published
Abstract [en]

PURPOSE: Childhood trauma in an important public health concern, and there is a need for brief and easily administered assessment tools. The Early Trauma Inventory (ETI) is one such instrument. The aim of this paper is to test the psychometric properties of the Swedish translation of the short, self-rated version (ETISR-SF), and to further validate the instrument.

MATERIALS AND METHODS: In this cross-sectional study, 243 psychiatric patients from an open care unit in Sweden and 56 controls were recruited. Participants were interviewed and thereafter completed the ETISR-SF. Internal consistency was calculated using Cronbach's alpha, a confirmatory factor analysis (CFA) was performed and goodness-of-fit was determined. Intra Class Correlation (ICC) was used to calculate test-retest reliability. Discriminant validity between groups was gauged using the Mann-Whitney U-test.

RESULTS: Cronbach's alpha varied between 0.55 and 0.76, with higher values in clinical samples than in controls. Of the four domains, general trauma showed a lower alpha than the other domains. The CFA confirmed the four-factor model previously seen and showed good to acceptable fit. The ICC value was 0.93, indicating good test-retest reliability. According to the Mann-Whitney U-test, the non-clinical sample differed significantly from the clinical sample, as did those with PTSD or borderline diagnosis from those without these diagnoses.

CONCLUSIONS: The Swedish translation of the ETISR-SF was found to have similar psychometric properties as both the original version and translations. ETISR-SF scores could also distinguish between different diagnostic groups associated with various degrees of trauma, which supports its discriminant validity.

Keywords
Childhood trauma, ETI, Early Trauma Inventory, translation, validation
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-401789 (URN)10.1080/08039488.2018.1498127 (DOI)30900487 (PubMedID)
Available from: 2020-01-08 Created: 2020-01-08 Last updated: 2020-04-14Bibliographically approved
Tillman, K. K., Hakelius, M., Höijer, J., Ramklint, M., Ekselius, L., Nowinski, D. & Papadopoulos, F. (2019). Folate Deficiency Based Autism as an Orofacial Clefts/Neural Tube Defect Spectrum Disorder Reply [Letter to the editor]. Journal of the American Academy of Child and Adolescent Psychiatry, 58(11), 1127-1128
Open this publication in new window or tab >>Folate Deficiency Based Autism as an Orofacial Clefts/Neural Tube Defect Spectrum Disorder Reply
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2019 (English)In: Journal of the American Academy of Child and Adolescent Psychiatry, ISSN 0890-8567, E-ISSN 1527-5418, Vol. 58, no 11, p. 1127-1128Article in journal, Letter (Other academic) Published
National Category
Psychiatry Pediatrics
Identifiers
urn:nbn:se:uu:diva-408056 (URN)10.1016/j.jaac.2019.06.005 (DOI)000518534100015 ()31655724 (PubMedID)
Note

Reply to: Sheldon B. Zablow: Folate Deficiency Based Autism as an Orofacial Clefts/Neural Tube Defect Spectrum Disorder, Journal of the American Academy of Child & Adolescent Psychiatry, Volume 58, Issue 11, November 2019, Pages 1126-1127

Available from: 2020-04-03 Created: 2020-04-03 Last updated: 2020-04-03Bibliographically approved
Flood, L., Korol, S., Ekselius, L., Birnir, B. & Jin, Z. (2019). Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons. Journal of Neuroimmunology, 337, Article ID UNSP 577050.
Open this publication in new window or tab >>Interferon-gamma potentiates GABA(A) receptor-mediated inhibitory currents in rat hippocampal CA1 pyramidal neurons
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2019 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 337, article id UNSP 577050Article in journal (Refereed) Published
Abstract [en]

The neural transmission and plasticity can be differentially modulated by various elements of the immune system. Interferon-gamma (IFN-gamma) is a "pro-inflammatory" cytokine mainly produced by T lymphocytes, activates its corresponding receptor and plays important roles under both homeostatic and inflammatory conditions. However, the impact of IFN-gamma on the gamma-aminobutyric acid (GABA)-mediated currents in the hippocampus, a major brain region involved in the cognitive function, has not been investigated. Here we detected abundant expression of both IFN-gamma receptor subunit gene transcripts (Ifngrl and Ifngr2) in the rat hippocampus by quantitative PCR. In addition, we pre-incubated rat hippocampal slices with IFN-gamma (100 ng/ml) and recorded GABA-activated spontaneous and miniature postsynaptic inhibitory currents (sIPSCs and mIPSCs) and tonic currents in hippocampal CAl pyramidal neurons by the whole-cell patch-clamp method. The pre-incubation with IFN-gamma increased the frequency but not the mean amplitude, rise time or decay time of both sIPSCs and mIPSCs in hippocampal CAl pyramidal neurons, suggesting a presynaptic effect of IFN-gamma. Moreover, the GABA-activated tonic currents were enhanced by IFN-gamma. In conclusion, the potentiation of GABAergic currents in hippocampal neurons by IFN-gamma may contribute to the disturbed neuronal excitability and cognitive dysfunction during neuroinflammation.

Place, publisher, year, edition, pages
ELSEVIER, 2019
Keywords
gamma-Aminobutyric acid, Hippocampus, Interferon-gamma, Phasic inhibition, Tonic inhibition
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-400001 (URN)10.1016/j.jneuroim.2019.577050 (DOI)000498318800004 ()31505410 (PubMedID)
Funder
Swedish Research Council, Dnr 201502417Swedish Research Council, 2018-02952The Swedish Brain Foundation
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2019-12-19Bibliographically approved
Axfors, C., Eckerdal, P., Volgsten, H., Wikström, A.-K., Ekselius, L., Ramklint, M., . . . Skalkidou, A. (2019). Investigating the association between neuroticism and adverse obstetric and neonatal outcomes. Scientific Reports, 9, Article ID 15470.
Open this publication in new window or tab >>Investigating the association between neuroticism and adverse obstetric and neonatal outcomes
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2019 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 15470Article in journal (Refereed) Published
Abstract [en]

Neuroticism is not only associated with affective disorders but also with certain somatic health problems. However, studies assessing whether neuroticism is associated with adverse obstetric or neonatal outcomes are scarce. This observational study comprises first-time mothers (n = 1969) with singleton pregnancies from several cohorts based in Uppsala, Sweden. To assess neuroticism-related personality, the Swedish universities Scales of Personality was used. Swedish national health registers were used to extract outcomes and confounders. In logistic regression models, odds ratios (ORs) with 95% confidence intervals (Cis) were calculated for the outcomes by an increase of 63 units of neuroticism (equalling the interquartile range). Analyses were adjusted for maternal age, educational level, height, body mass index, year of delivery, smoking during pregnancy, involuntary childlessness, and psychiatric morbidity. Main outcomes were mode of delivery, gestational diabetes mellitus, gestational hypertension, preeclampsia, induction of delivery, prolonged delivery, severe lacerations, placental retention, postpartum haemorrhage, premature birth, infant born small or large for gestational age, and Apgar score. Neuroticism was not independently associated with adverse obstetric or neonatal outcomes besides gestational diabetes. For future studies, models examining sub-components of neuroticism or pregnancy-specific anxiety are encouraged.

National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
urn:nbn:se:uu:diva-397118 (URN)10.1038/s41598-019-51861-y (DOI)000493048400023 ()31664086 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2007-1955Swedish Research Council, 521-2010-3293Swedish Research Council, K2008-54 x - 20642-01-3Marianne and Marcus Wallenberg Foundation, MMW2011.0115Swedish Society of Medicine, SLS-250581
Available from: 2019-11-15 Created: 2019-11-15 Last updated: 2019-11-15Bibliographically approved
Axfors, C., Hellgren, C., Volgsten, H., Skoog Svanberg, A., Ekselius, L., Wikström, A.-K., . . . Sundström-Poromaa, I. (2019). Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women. Acta Obstetricia et Gynecologica Scandinavica, 98(4), 470-478
Open this publication in new window or tab >>Neuroticism is associated with higher antenatal care utilization in obstetric low-risk women
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2019 (English)In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 98, no 4, p. 470-478Article in journal (Refereed) Published
Abstract [en]

Introduction

Elevated neuroticism is associated with higher health care utilization in the general population. This study aimed to investigate the association between neuroticism and the use of publicly financed antenatal care in obstetric low‐risk women, taking predisposing and need factors for health care utilization into consideration.

Material and methods

Participants comprised 1052 obstetric low‐risk women (no chronic diseases or adverse pregnancy conditions) included in several obstetrics/gynecology studies in Uppsala, Sweden. Neuroticism was self‐rated on the Swedish universities Scales of Personality. Medical records of their first subsequent pregnancy were scanned for antenatal care use. Associations between antenatal care use and neuroticism were analyzed with logistic regression (binary outcomes) or negative binomial regression (count outcomes) comparing the 75th and 25th neuroticism percentiles. Depending on the Akaike information criterion the exposure was modeled as either linear or with restricted cubic splines. Analyses were adjusted for predisposing (sociodemographic and parity) and need factors (body mass index and psychiatric morbidity).

Results

After adjustment, women with higher neuroticism had more fetal ultrasounds (incidence rate ratio = 1.09, 95% confidence interval (CI) 1.02‐1.16), more emergency visits to an obstetrician/gynecologist (incidence rate ratio = 1.22, 95% CI 1.03‐1.45) and were more likely to visit a fear‐of‐childbirth clinic (odds ratio = 2.71, 95% CI 1.71‐4.29). Moreover, they more often consulted midwives in specialized antenatal care facilities (significant J‐shaped association).

Conclusions

Neuroticism was associated with higher utilization of publicly financed antenatal care in obstetric low‐risk women, even after adjusting for predisposing and need factors. Future studies should address the benefits of interventions as a complement to routine antenatal care programs to reduce subclinical anxiety.

Keywords
antenatal care, health care utilization, neuroticism, personality, pregnancy, prenatal care
National Category
Obstetrics, Gynecology and Reproductive Medicine
Research subject
Obstetrics and Gynaecology
Identifiers
urn:nbn:se:uu:diva-364260 (URN)10.1111/aogs.13506 (DOI)000460954800008 ()30457176 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and Welfare, 2007-1955Marianne and Marcus Wallenberg Foundation, MMW2011.0115The Swedish Medical Association, SLS-250581Swedish Research Council, 521-2010-3293Swedish Research Council, K2008-54X-20642-01-3Swedish Society of MedicineStiftelsen Söderström - Königska sjukhemmetTore Nilsons Stiftelse för medicinsk forskning
Available from: 2018-10-24 Created: 2018-10-24 Last updated: 2019-04-15Bibliographically 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: 2020-01-09Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-5760-7730

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