Immune system dysregulation in first-onset postpartum psychosis

V. Bergink, K.M. Burgerhout, K. Weigelt, V.J.M. Pop, H. de Wit, R.C. Drexhage, S.A. Kushner, H.A. Drexhage

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background
Accumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered endocrine set point. Therefore, the aim of this study was to examine immune activation in patients with first-onset PP at the level of monocytes, T cells, and serum cytokines/chemokines.
Methods
We included 63 women admitted with first-onset PP. Control groups included healthy postpartum (n = 56) and nonpostpartum (n = 136) women. A quantitative-polymerase chain reaction monocyte gene expression analysis was performed with 43 genes previously identified as abnormally regulated in nonpostpartum mood disorder patients including the isoforms of the glucocorticoid receptor. Peripheral blood mononuclear cells percentages were measured by fluorescence-activated cell sorter analysis, whereas serum cytokines/chemokines were determined with a cytometric bead array.
Results
In healthy women, postpartum T cell levels were significantly elevated compared with nonpostpartum. Patients with PP failed to show the normal postpartum T cell elevation. In contrast, these patients showed a significant elevation of monocyte levels and a significant upregulation of several immune-related monocyte genes compared with control subjects postpartum and nonpostpartum. Furthermore, the glucocorticoid receptor α/β gene expression ratio was decreased in monocytes of PP patients, strongly correlating with their immune activation.
Conclusions
This study demonstrates a robust dysregulation of the immuno-neuro-endocrine set point in PP, with a notable over-activation of the monocyte/macrophage arm of the immune system.
Keywords: Bipolar disorder; cytokines; gene expression; glucocorticoid receptor; postpartum psychosis; T cells
Original languageEnglish
Pages (from-to)1000-1007
JournalBiological Psychiatry
Volume73
Issue number10
DOIs
Publication statusPublished - 2013

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Immune System
Macrophage Activation
Serum
Up-Regulation
Fluorescence
Polymerase Chain Reaction

Cite this

Bergink, V., Burgerhout, K. M., Weigelt, K., Pop, V. J. M., de Wit, H., Drexhage, R. C., ... Drexhage, H. A. (2013). Immune system dysregulation in first-onset postpartum psychosis. Biological Psychiatry, 73(10), 1000-1007. https://doi.org/10.1016/j.biopsych.2012.11.006
Bergink, V. ; Burgerhout, K.M. ; Weigelt, K. ; Pop, V.J.M. ; de Wit, H. ; Drexhage, R.C. ; Kushner, S.A. ; Drexhage, H.A. / Immune system dysregulation in first-onset postpartum psychosis. In: Biological Psychiatry. 2013 ; Vol. 73, No. 10. pp. 1000-1007.
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title = "Immune system dysregulation in first-onset postpartum psychosis",
abstract = "BackgroundAccumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered endocrine set point. Therefore, the aim of this study was to examine immune activation in patients with first-onset PP at the level of monocytes, T cells, and serum cytokines/chemokines.MethodsWe included 63 women admitted with first-onset PP. Control groups included healthy postpartum (n = 56) and nonpostpartum (n = 136) women. A quantitative-polymerase chain reaction monocyte gene expression analysis was performed with 43 genes previously identified as abnormally regulated in nonpostpartum mood disorder patients including the isoforms of the glucocorticoid receptor. Peripheral blood mononuclear cells percentages were measured by fluorescence-activated cell sorter analysis, whereas serum cytokines/chemokines were determined with a cytometric bead array.ResultsIn healthy women, postpartum T cell levels were significantly elevated compared with nonpostpartum. Patients with PP failed to show the normal postpartum T cell elevation. In contrast, these patients showed a significant elevation of monocyte levels and a significant upregulation of several immune-related monocyte genes compared with control subjects postpartum and nonpostpartum. Furthermore, the glucocorticoid receptor α/β gene expression ratio was decreased in monocytes of PP patients, strongly correlating with their immune activation.ConclusionsThis study demonstrates a robust dysregulation of the immuno-neuro-endocrine set point in PP, with a notable over-activation of the monocyte/macrophage arm of the immune system.Keywords: Bipolar disorder; cytokines; gene expression; glucocorticoid receptor; postpartum psychosis; T cells",
author = "V. Bergink and K.M. Burgerhout and K. Weigelt and V.J.M. Pop and {de Wit}, H. and R.C. Drexhage and S.A. Kushner and H.A. Drexhage",
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Bergink, V, Burgerhout, KM, Weigelt, K, Pop, VJM, de Wit, H, Drexhage, RC, Kushner, SA & Drexhage, HA 2013, 'Immune system dysregulation in first-onset postpartum psychosis', Biological Psychiatry, vol. 73, no. 10, pp. 1000-1007. https://doi.org/10.1016/j.biopsych.2012.11.006

Immune system dysregulation in first-onset postpartum psychosis. / Bergink, V.; Burgerhout, K.M.; Weigelt, K.; Pop, V.J.M.; de Wit, H.; Drexhage, R.C.; Kushner, S.A.; Drexhage, H.A.

In: Biological Psychiatry, Vol. 73, No. 10, 2013, p. 1000-1007.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Pop, V.J.M.

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AU - Drexhage, R.C.

AU - Kushner, S.A.

AU - Drexhage, H.A.

PY - 2013

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N2 - BackgroundAccumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered endocrine set point. Therefore, the aim of this study was to examine immune activation in patients with first-onset PP at the level of monocytes, T cells, and serum cytokines/chemokines.MethodsWe included 63 women admitted with first-onset PP. Control groups included healthy postpartum (n = 56) and nonpostpartum (n = 136) women. A quantitative-polymerase chain reaction monocyte gene expression analysis was performed with 43 genes previously identified as abnormally regulated in nonpostpartum mood disorder patients including the isoforms of the glucocorticoid receptor. Peripheral blood mononuclear cells percentages were measured by fluorescence-activated cell sorter analysis, whereas serum cytokines/chemokines were determined with a cytometric bead array.ResultsIn healthy women, postpartum T cell levels were significantly elevated compared with nonpostpartum. Patients with PP failed to show the normal postpartum T cell elevation. In contrast, these patients showed a significant elevation of monocyte levels and a significant upregulation of several immune-related monocyte genes compared with control subjects postpartum and nonpostpartum. Furthermore, the glucocorticoid receptor α/β gene expression ratio was decreased in monocytes of PP patients, strongly correlating with their immune activation.ConclusionsThis study demonstrates a robust dysregulation of the immuno-neuro-endocrine set point in PP, with a notable over-activation of the monocyte/macrophage arm of the immune system.Keywords: Bipolar disorder; cytokines; gene expression; glucocorticoid receptor; postpartum psychosis; T cells

AB - BackgroundAccumulating evidence suggests that dysregulation of the immune system represents an important vulnerability factor for mood disorders. Postpartum psychosis (PP) is a severe mood disorder occurring within 4 weeks after delivery, a period of heightened immune responsiveness and an altered endocrine set point. Therefore, the aim of this study was to examine immune activation in patients with first-onset PP at the level of monocytes, T cells, and serum cytokines/chemokines.MethodsWe included 63 women admitted with first-onset PP. Control groups included healthy postpartum (n = 56) and nonpostpartum (n = 136) women. A quantitative-polymerase chain reaction monocyte gene expression analysis was performed with 43 genes previously identified as abnormally regulated in nonpostpartum mood disorder patients including the isoforms of the glucocorticoid receptor. Peripheral blood mononuclear cells percentages were measured by fluorescence-activated cell sorter analysis, whereas serum cytokines/chemokines were determined with a cytometric bead array.ResultsIn healthy women, postpartum T cell levels were significantly elevated compared with nonpostpartum. Patients with PP failed to show the normal postpartum T cell elevation. In contrast, these patients showed a significant elevation of monocyte levels and a significant upregulation of several immune-related monocyte genes compared with control subjects postpartum and nonpostpartum. Furthermore, the glucocorticoid receptor α/β gene expression ratio was decreased in monocytes of PP patients, strongly correlating with their immune activation.ConclusionsThis study demonstrates a robust dysregulation of the immuno-neuro-endocrine set point in PP, with a notable over-activation of the monocyte/macrophage arm of the immune system.Keywords: Bipolar disorder; cytokines; gene expression; glucocorticoid receptor; postpartum psychosis; T cells

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SN - 0006-3223

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Bergink V, Burgerhout KM, Weigelt K, Pop VJM, de Wit H, Drexhage RC et al. Immune system dysregulation in first-onset postpartum psychosis. Biological Psychiatry. 2013;73(10):1000-1007. https://doi.org/10.1016/j.biopsych.2012.11.006