Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder

F Benedetti, S Poletti, TA Hoogenboezem, C Locatelli, H De Wit, AJM Wijkhuijs, C Colombo, HA Drexhage

Research output: Contribution to journalArticle

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Abstract

Background: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. Methods: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls. Thirty-one patients (84%) had a lifetime history of drug resistance. Patients were administered 3 TSD + LT cycles in 1 week (study period: 2010-2012). Data were analyzed with age-and false-discovery-rate-corrected analysis of variance and were tested as predictors in a regressive model. Results: Twenty-three patients (62%) responded to treatment (Inventory of Depressive Symptomatology IDS-C score < 12). Five highly intercorrelated compounds (IL-8, MCP-1, IFN-γ, IL-6, TNF-α) showed higher levels in nonresponder patients as compared to responders, corrected for multiple comparisons (respectively F = 6.138, P FDR =.0134; F = 6.197, P FDR =.0134; F = 4.785, P FDR =.0255; F = 3.782, P FDR =.0441; F = 3.764, P FDR =.0441). A principal component analysis identified a single component that explained 84% of variance of these cytokines (Q 2 = 0.15), and a high factor score significantly predicted worse response (b = -0.692; W = 4.34, P =.037). A higher body mass index correlated with higher cytokines (r = 0.430, P =.010), indirectly hampering response (b = -0.0192, P =.013). Conclusions: Proinflammatory compounds reflecting an M1-like proinflammatory state of monocytes/macrophages are associated with a poor response to antidepressant TSD + LT treatment in bipolar depression. © Copyright 2017 Physicians Postgraduate Press, Inc.
Original languageEnglish
Pages (from-to)e986-e993
JournalJournal of Clinical Psychiatry
Volume78
Issue number8
DOIs
Publication statusPublished - 2017

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Bipolar Disorder
Antidepressive Agents
Sleep Deprivation
Phototherapy
Cytokines
Neuronal Plasticity
Photoperiod
Principal Component Analysis
Interleukin-8
Drug Resistance
Neurotransmitter Agents
Inpatients
Monocytes
Interleukin-6
Analysis of Variance
Body Mass Index
Therapeutics
Macrophages
Physicians
Equipment and Supplies

Cite this

Benedetti, F., Poletti, S., Hoogenboezem, TA., Locatelli, C., De Wit, H., Wijkhuijs, AJM., ... Drexhage, HA. (2017). Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder. Journal of Clinical Psychiatry, 78(8), e986-e993. https://doi.org/10.4088/JCP.16m11310

Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder. / Benedetti, F; Poletti, S; Hoogenboezem, TA; Locatelli, C; De Wit, H; Wijkhuijs, AJM; Colombo, C; Drexhage, HA.

In: Journal of Clinical Psychiatry, Vol. 78, No. 8, 2017, p. e986-e993.

Research output: Contribution to journalArticle

Benedetti, F, Poletti, S, Hoogenboezem, TA, Locatelli, C, De Wit, H, Wijkhuijs, AJM, Colombo, C & Drexhage, HA 2017, 'Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder', Journal of Clinical Psychiatry, vol. 78, no. 8, pp. e986-e993. https://doi.org/10.4088/JCP.16m11310
Benedetti, F ; Poletti, S ; Hoogenboezem, TA ; Locatelli, C ; De Wit, H ; Wijkhuijs, AJM ; Colombo, C ; Drexhage, HA. / Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder. In: Journal of Clinical Psychiatry. 2017 ; Vol. 78, No. 8. pp. e986-e993.
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abstract = "Background: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. Methods: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls. Thirty-one patients (84{\%}) had a lifetime history of drug resistance. Patients were administered 3 TSD + LT cycles in 1 week (study period: 2010-2012). Data were analyzed with age-and false-discovery-rate-corrected analysis of variance and were tested as predictors in a regressive model. Results: Twenty-three patients (62{\%}) responded to treatment (Inventory of Depressive Symptomatology IDS-C score < 12). Five highly intercorrelated compounds (IL-8, MCP-1, IFN-γ, IL-6, TNF-α) showed higher levels in nonresponder patients as compared to responders, corrected for multiple comparisons (respectively F = 6.138, P FDR =.0134; F = 6.197, P FDR =.0134; F = 4.785, P FDR =.0255; F = 3.782, P FDR =.0441; F = 3.764, P FDR =.0441). A principal component analysis identified a single component that explained 84{\%} of variance of these cytokines (Q 2 = 0.15), and a high factor score significantly predicted worse response (b = -0.692; W = 4.34, P =.037). A higher body mass index correlated with higher cytokines (r = 0.430, P =.010), indirectly hampering response (b = -0.0192, P =.013). Conclusions: Proinflammatory compounds reflecting an M1-like proinflammatory state of monocytes/macrophages are associated with a poor response to antidepressant TSD + LT treatment in bipolar depression. {\circledC} Copyright 2017 Physicians Postgraduate Press, Inc.",
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T1 - Higher baseline proinflammatory cytokines mark poor antidepressant response in bipolar disorder

AU - Benedetti, F

AU - Poletti, S

AU - Hoogenboezem, TA

AU - Locatelli, C

AU - De Wit, H

AU - Wijkhuijs, AJM

AU - Colombo, C

AU - Drexhage, HA

PY - 2017

Y1 - 2017

N2 - Background: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. Methods: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls. Thirty-one patients (84%) had a lifetime history of drug resistance. Patients were administered 3 TSD + LT cycles in 1 week (study period: 2010-2012). Data were analyzed with age-and false-discovery-rate-corrected analysis of variance and were tested as predictors in a regressive model. Results: Twenty-three patients (62%) responded to treatment (Inventory of Depressive Symptomatology IDS-C score < 12). Five highly intercorrelated compounds (IL-8, MCP-1, IFN-γ, IL-6, TNF-α) showed higher levels in nonresponder patients as compared to responders, corrected for multiple comparisons (respectively F = 6.138, P FDR =.0134; F = 6.197, P FDR =.0134; F = 4.785, P FDR =.0255; F = 3.782, P FDR =.0441; F = 3.764, P FDR =.0441). A principal component analysis identified a single component that explained 84% of variance of these cytokines (Q 2 = 0.15), and a high factor score significantly predicted worse response (b = -0.692; W = 4.34, P =.037). A higher body mass index correlated with higher cytokines (r = 0.430, P =.010), indirectly hampering response (b = -0.0192, P =.013). Conclusions: Proinflammatory compounds reflecting an M1-like proinflammatory state of monocytes/macrophages are associated with a poor response to antidepressant TSD + LT treatment in bipolar depression. © Copyright 2017 Physicians Postgraduate Press, Inc.

AB - Background: The clinical relevance of raised levels of circulating cytokines in bipolar disorder is still unclear. Cytokines influence neurotransmitters, neuroplasticity, and white matter integrity. An inconsistent literature suggests that higher cytokine levels could hamper antidepressant response. Total sleep deprivation (TSD) and light therapy (LT) prompt a rapid antidepressant response and can provide a model treatment to study predictors of response. Methods: We studied at baseline 15 immune-regulating compounds in 37 consecutively admitted inpatients with a major depressive episode in the course of bipolar disorder (DSM-5 criteria) and in 24 controls. Thirty-one patients (84%) had a lifetime history of drug resistance. Patients were administered 3 TSD + LT cycles in 1 week (study period: 2010-2012). Data were analyzed with age-and false-discovery-rate-corrected analysis of variance and were tested as predictors in a regressive model. Results: Twenty-three patients (62%) responded to treatment (Inventory of Depressive Symptomatology IDS-C score < 12). Five highly intercorrelated compounds (IL-8, MCP-1, IFN-γ, IL-6, TNF-α) showed higher levels in nonresponder patients as compared to responders, corrected for multiple comparisons (respectively F = 6.138, P FDR =.0134; F = 6.197, P FDR =.0134; F = 4.785, P FDR =.0255; F = 3.782, P FDR =.0441; F = 3.764, P FDR =.0441). A principal component analysis identified a single component that explained 84% of variance of these cytokines (Q 2 = 0.15), and a high factor score significantly predicted worse response (b = -0.692; W = 4.34, P =.037). A higher body mass index correlated with higher cytokines (r = 0.430, P =.010), indirectly hampering response (b = -0.0192, P =.013). Conclusions: Proinflammatory compounds reflecting an M1-like proinflammatory state of monocytes/macrophages are associated with a poor response to antidepressant TSD + LT treatment in bipolar depression. © Copyright 2017 Physicians Postgraduate Press, Inc.

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DO - 10.4088/JCP.16m11310

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