28
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Dysregulation of leukocyte gene expression in women with medication-refractory depression versus healthy non-depressed controls

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background Depressive Disorders (DD) are a great financial and social burden. Females display 70% higher rate of depression than males and more than 30% of these patients do not respond to conventional medications. Thus medication-refractory female patients are a large, under-served, group where new biological targets for intervention are greatly needed. Methods We used real-time quantitative polymerase chain reaction (qPCR) to evaluate mRNA gene expression from peripheral blood leukocytes for 27 genes, including immune, HPA-axis, ion channels, and growth and transcription factors. Our sample included 23 females with medication refractory DD: 13 with major depressive disorder (MDD), 10 with bipolar disorder (BPD). Our comparison group was 19 healthy, non-depressed female controls. We examined differences in mRNA expression in DD vs. controls, in MDD vs. BPD, and in patients with greater vs. lesser depression severity. Results DD patients showed increased expression for IL-10, IL-6, OXTR, P2RX7, P2RY1, and TRPV1. BPD patients showed increased APP, CREB1, NFKB1, NR3C1, and SPARC and decreased TNF expression. Depression severity was related to increased IL-10, P2RY1, P2RX1, and TRPV4 expression. Conclusions These results support prior findings of dysregulation in immune genes, and provide preliminary evidence of dysregulation in purinergic and other ion channels in females with medication-refractory depression, and in transcription and growth factors in those with BPD. If replicated in future research examining protein levels as well as mRNA, these pathways could potentially be used to explore biological mechanisms of depression and to develop new drug targets.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: found
          • Article: not found

          Molecular evidence for BDNF- and GABA-related dysfunctions in the amygdala of female subjects with Major Depression

          Women are twice as likely as men to develop major depressive disorder (MDD) and are more prone to recurring episodes. Hence, we tested the hypothesis that the illness may associate with robust molecular changes in female subjects, and investigated large-scale gene expression in the postmortem brain of MDD subjects paired with matched controls (n=21 pairs). We focused on the lateral/basolateral/basomedian (LBNC) complex of the amygdala as a neural hub of mood regulation affected in MDD. Among the most robust findings were downregulated transcripts for genes coding for GABA interneuron-related peptides, including somatostatin (SST), tachykinin, neuropeptide Y (NPY) and cortistatin, in a pattern reminiscent to that previously reported in mice with low BDNF. Changes were confirmed by quantitative PCR and not explained by demographic, technical or known clinical parameters. BDNF itself was significantly downregulated at the RNA and protein levels in MDD subjects. Investigating putative mechanisms, we show that this core MDD-related gene profile (including SST, NPY, TAC1, RGS4, CORT) is recapitulated by complementary patterns in mice with constitutive (BDNF-heterozygous) or activity-dependent (Exon IV knockout) decreases in BDNF function, with a common effect on SST and NPY. Together, these results provide both direct (low RNA/protein) and indirect (low BDNF-dependent gene pattern) evidence for reduced BDNF function in the amygdala of female subjects with MDD. Supporting studies in mutant mice models suggest a complex mechanism of low constitutive and activity-dependent BDNF function in MDD, particularly affecting SST/NPY-related GABA neurons, thus linking the neurotrophic and GABA hypotheses of depression.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Immune suppression and immune activation in depression.

            Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, and CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging pre-clinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities. Copyright © 2010 Elsevier Inc. All rights reserved.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A detailed examination of cytokine abnormalities in Major Depressive Disorder.

              Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). Twenty cytokines were simultaneously assessed in 49 individuals with MDD and 49 age and gender matched controls. Multiple pro-inflammatory and two anti-inflammatory cytokines were significantly elevated in the MDD sample, including an antidepressant naïve subset. These data support a generalized chronic inflammatory state in MDD, and implicate additional cytokines and chemokines previously linked to cardiovascular disease.
                Bookmark

                Author and article information

                Contributors
                Journal
                BMC Psychiatry
                BMC Psychiatry
                BMC Psychiatry
                BioMed Central
                1471-244X
                2013
                21 October 2013
                : 13
                : 273
                Affiliations
                [1 ]Department of Anesthesiology, University of Utah Health Sciences Center, Salt Lake City, UT, USA
                [2 ]Department of Exercise and Sport Science, University of Utah, USA, Salt Lake City, UT, USA
                [3 ]Department of Psychiatry, University of Utah, Salt Lake City, UT, USA
                [4 ]Neuroscience Program, University of Utah Health Sciences Center, Salt Lake City, UT, USA
                Article
                1471-244X-13-273
                10.1186/1471-244X-13-273
                4015603
                24143878
                8ccd7a7a-fd22-4be7-80fc-c2762b1416cb
                Copyright © 2013 Iacob et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 May 2013
                : 7 October 2013
                Categories
                Research Article

                Clinical Psychology & Psychiatry
                depression,bipolar disorder,medication-refractory,females,qpcr,gene expression,immune,purinergic receptor,transient vanilloid receptor,amyloid precursor protein,oxytocin

                Comments

                Comment on this article