Dataset Information

Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression.

ABSTRACT: Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.

SUBMITTER: Dmitrzak-Weglarz M

PROVIDER: S-EPMC8107693 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression.

Dmitrzak-Weglarz Monika M Banach Ewa E Bilska Karolina K Narozna Beata B Szczepankiewicz Aleksandra A Reszka Edyta E Jablonska Ewa E Kapelski Paweł P Skibinska Maria M Pawlak Joanna J

Frontiers in pharmacology 20210426

Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the p ...[more]

PMID: 33981243

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Project description:ImportanceBipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools.ObjectiveTo identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information.Design, setting, and participantsThis diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023.Main outcomes and measuresPatient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview.ResultsOf 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001).Conclusions and relevanceThis study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.

Dataset Information

Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression.

Publications

Molecular Regulation of the Melatonin Biosynthesis Pathway in Unipolar and Bipolar Depression.

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