Episode-Specific Differential Gene Expression of Peripheral Blood Mononuclear Cells in Rapid Cycling Supports Novel Treatment Approaches

Begemann, Martin; Sargin, Derya; Rossner, Moritz J.; Bartels, Claudia; Theis, Fabian J.; Wichert, Sven P.; Stender, Nike; Fischer, B.; Sperling, Swetlana; Stawicki, Sabina; Wiedl, Anne; Falkai, Peter; Nave, Klaus‐Armin; Ehrenreich, Hannelore

doi:10.2119/2008-00053.begemann

Cited by 25 publications

(32 citation statements)

References 41 publications

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“…As suggested by our results in responder and nonresponder patients, gene expression variation of selected genes, monitored across a long period of time, could be informative of clinical evolution and potential relapses or recurrences. This has also been proposed by Begemann et al [47] in a case report describing a patient with rapid-cycling bipolar disorder. It remains uncertain what may cause stable treatment response, and relapse or recurrence during mood disorders [48].…”

Section: Discussionsupporting

confidence: 56%

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

et al. 2014

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Background: Mood disorders are frequently characterized by uncertain prognosis and studying mRNA expression variations in blood cells represents a promising avenue of identifying biomarkers for mood disorders. State-dependent gene expression variations have been described during a major depressive episode (MDE), in particular for SLC6A4 mRNA, but how this transcript varies in relation to MDE evolution remains unclear. In this study, we prospectively assessed time trends of SCL6A4 mRNA expression in responder and nonresponder patients. Methods: We examined SLC6A4 mRNA expression in blood samples from 13 patients treated for severe MDE and their matched controls by reverse transcription and quantitative PCR. All subjects were followed for 30 weeks. Patients were classified as either responders or nonresponders based on improvement of depression according to the 17-item Hamilton Depression Rating Scale. Using a longitudinal design, we ascertained mRNA expression at baseline, 2, 8, and 30 weeks and compared mRNA expression between responder and nonresponder patients, and matched controls. Results: We observed a decrease of SLC6A4 mRNA expression in responder patients across a 30-week follow-up, while nonresponder patients exhibited up-regulated SLC6A4 mRNA. Conclusion: Peripheral SLC6A4 mRNA expression could serve as a biomarker for monitoring and follow-up during an MDE and may help to more appropriately select individualized treatments.

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Section: Discussionsupporting

confidence: 56%

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

et al. 2014

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“…An interesting result shows the description of a case of therapy resistant bipolar disorder with a rapid cycling course. In this case, a therapeutic long-term benefit from celecoxib has been described, in parallel with the downregulation of the RNA-gene expression of products of the prostaglandin metabolism (Begemann et al 2008). …”

Section: Cox-2 Inhibition As a Possible Antiinflammatory Therapeutic mentioning

confidence: 93%

“…Regarding bipolar disorder, there are only a few data on COX-2-inhibitors (Begemann et al 2008;Nery et al 2008). One double-blind, randomized add-on study has been performed with celecoxib in 28 patients during a depressed or mixed episode of bipolar disorder over 6 weeks.…”

Section: Cox-2 Inhibition As a Possible Antiinflammatory Therapeutic mentioning

confidence: 99%

Inflammatory Biomarkers and Depression

2010

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Antidepressants, predominantly serotonin- and/or noradrenaline reuptake inhibiting drugs have several shortcomings. The exact pathophysiological mechanisms leading to serotonergic-, noradrenergic- or dopaminergic dysfunction are still unclear. An inflammatory mechanism has been postulated and will be discussed here including possible therapeutic advantages of cyclooxygenase-2 (COX-2) inhibitors. Differences in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan-kynurenine metabolism resulting in an increased tryptophan and serotonin degradation and probably in an increased production of quinolinic acid might play a key role in major depression (MD). These differences are associated with an imbalance in the glutamatergic neurotransmission, which may contribute to an overweight of N-methyl-D: -aspartate agonism in MD. The immunological imbalance results in an increased prostaglandin E₂ production and probably also in an increased COX-2 expression. Although there is strong evidence for the view that the interactions of the immune system, IDO, the serotonergic system and the glutamatergic neurotransmission play a key role in MD, several gaps, e.g. the roles of genetics, disease course, sex, different psychopathological states, etc., have to be bridged by intense further research. There were already hints that anti-inflammatory therapy might have beneficial effects in MD. COX-2 inhibitors, however, have been tested in animal models and in preliminary clinical studies showing favourable effects compared to placebo in MD. The effects of COX-2 inhibition in the CNS as well as the different components of the inflammatory system, the kynurenine-metabolism and the glutamatergic neurotransmission, however, still need careful further scientific evaluation including clinical studies in bigger samples of patients.

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“…Previously, these genes have been associated with psychiatric disorders such as BD, major affective disorder, SZ, and anxiety. PTGDS is involved in the synthesis of PGD 2 from PGH 2 , the cyclooxygenase-mediated product of arachidonic acid which is a PUFA [4]. PTGDS is a top anxiety gene modulated by changes in PUFA (omega-3 fatty acid docosahexaenoic acid) [73] on the convergent functional genomics scale.…”

Section: Discussionmentioning

confidence: 99%

“…A growing body of work has demonstrated the potential utility of RNA diagnostic tools with peripheral samples such as whole blood, peripheral blood mononuclear cells (PBMCs), and lymphoblastic cell lines in multiple studies of SZ and BD [4-12]. There have also been large studies that have used whole genome RNA expression to compare healthy controls and patients with disorders such as Alzheimer disease [13], autism [14], Down syndrome [15], epilepsy [16], Tourette syndrome [16], Huntington disease [17], Klinefelter syndrome [18], multiple sclerosis [19], smoking and major depression [20], panic disorder [21], posttraumatic stress disorder [22], and subjective social isolation (loneliness) [23].…”

Section: Introductionmentioning

confidence: 99%

Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder

et al. 2017

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This study developed potential blood-based biomarker tests for diagnosing and differentiating schizophrenia (SZ), bipolar disorder type I (BD), and normal control (NC) subjects using mRNA gene expression signatures. A total of 90 subjects (n = 30 each for the three groups of subjects) provided blood samples at two visits. The Affymetrix exon microarray was used to profile the expression of over 1.4 million probesets. We selected potential biomarker panels using the temporal stability of the probesets and also back-tested them at two different visits for each subject. The 18-gene biomarker panels, using logistic regression modeling, correctly differentiated the three groups of subjects with high accuracy across the two different clinical visits (83–88% accuracy). The results are also consistent with the actual data and the “leave-one-out” analyses, indicating that the models should be predictive when applied to independent data cohorts. Many of the SZ and BD subjects were taking antipsychotic and mood stabilizer medications at the time of blood draw, raising the possibility that these drugs could have affected some of the differential transcription signatures. Using an independent Illumina data set of gene expression data from antipsychotic medication-free SZ subjects, the 18-gene biomarker panels produced a receiver operating characteristic curve accuracy greater than 0.866 in patients that were less than 30 years of age and medication free. We confirmed select transcripts by quantitative PCR and the nCounter® System. The episodic nature of psychiatric disorders might lead to highly variable results depending on when blood is collected in relation to the severity of the disease/symptoms. We have found stable trait gene panel markers for lifelong psychiatric disorders that may have diagnostic utility in younger undiagnosed subjects where there is a critical unmet need. The study requires replication in subjects for ultimate proof of the utility of the differential diagnosis.

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Episode-Specific Differential Gene Expression of Peripheral Blood Mononuclear Cells in Rapid Cycling Supports Novel Treatment Approaches

Cited by 25 publications

References 41 publications

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

Longitudinal Monitoring of the Serotonin Transporter Gene Expression to Assess Major Depressive Episode Evolution

Inflammatory Biomarkers and Depression

Exon Array Biomarkers for the Differential Diagnosis of Schizophrenia and Bipolar Disorder

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