Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder

Ole Köhler-Forsberg, Louisa Sylvia, Thilo Deckersbach, Michael Joshua Ostacher, Melvin McInnis, Dan Iosifescu, Charles Bowden, Susan McElroy, Joseph Calabrese, Michael Thase, Richard Charles Shelton, Mauricio Tohen, James Kocsis, Edward Friedman, Terence Ketter, Andrew Alan Nierenberg

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. Methods: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. Results: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Conclusion: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalActa Neuropsychiatrica
DOIs
StateAccepted/In press - Dec 7 2017

Fingerprint

Bipolar Disorder
Immune System
Leukocytes
Appetite
Psychopathology
Regression Analysis
Clinical Trials
Depression
Mood Disorders
Leukocyte Count
Lithium
Fatigue
Linear Models
Analysis of Variance
Sleep
Body Mass Index
Biomarkers
Smoking
Health

Keywords

  • affective disorder
  • bipolar disorder
  • clinical trials
  • lithium
  • mood stabilisers
  • psychoneuroimmunology

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Köhler-Forsberg, O., Sylvia, L., Deckersbach, T., Ostacher, M. J., McInnis, M., Iosifescu, D., ... Nierenberg, A. A. (Accepted/In press). Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. Acta Neuropsychiatrica, 1-9. https://doi.org/10.1017/neu.2017.34

Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. / Köhler-Forsberg, Ole; Sylvia, Louisa; Deckersbach, Thilo; Ostacher, Michael Joshua; McInnis, Melvin; Iosifescu, Dan; Bowden, Charles; McElroy, Susan; Calabrese, Joseph; Thase, Michael; Shelton, Richard Charles; Tohen, Mauricio; Kocsis, James; Friedman, Edward; Ketter, Terence; Nierenberg, Andrew Alan.

In: Acta Neuropsychiatrica, 07.12.2017, p. 1-9.

Research output: Contribution to journalArticle

Köhler-Forsberg, O, Sylvia, L, Deckersbach, T, Ostacher, MJ, McInnis, M, Iosifescu, D, Bowden, C, McElroy, S, Calabrese, J, Thase, M, Shelton, RC, Tohen, M, Kocsis, J, Friedman, E, Ketter, T & Nierenberg, AA 2017, 'Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder', Acta Neuropsychiatrica, pp. 1-9. https://doi.org/10.1017/neu.2017.34
Köhler-Forsberg O, Sylvia L, Deckersbach T, Ostacher MJ, McInnis M, Iosifescu D et al. Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. Acta Neuropsychiatrica. 2017 Dec 7;1-9. https://doi.org/10.1017/neu.2017.34
Köhler-Forsberg, Ole ; Sylvia, Louisa ; Deckersbach, Thilo ; Ostacher, Michael Joshua ; McInnis, Melvin ; Iosifescu, Dan ; Bowden, Charles ; McElroy, Susan ; Calabrese, Joseph ; Thase, Michael ; Shelton, Richard Charles ; Tohen, Mauricio ; Kocsis, James ; Friedman, Edward ; Ketter, Terence ; Nierenberg, Andrew Alan. / Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder. In: Acta Neuropsychiatrica. 2017 ; pp. 1-9.
@article{07fab73fa51849d9955ffd67e55082f3,
title = "Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder",
abstract = "Objective: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. Methods: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. Results: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95{\%} CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95{\%} CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Conclusion: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.",
keywords = "affective disorder, bipolar disorder, clinical trials, lithium, mood stabilisers, psychoneuroimmunology",
author = "Ole K{\"o}hler-Forsberg and Louisa Sylvia and Thilo Deckersbach and Ostacher, {Michael Joshua} and Melvin McInnis and Dan Iosifescu and Charles Bowden and Susan McElroy and Joseph Calabrese and Michael Thase and Shelton, {Richard Charles} and Mauricio Tohen and James Kocsis and Edward Friedman and Terence Ketter and Nierenberg, {Andrew Alan}",
year = "2017",
month = "12",
day = "7",
doi = "10.1017/neu.2017.34",
language = "English (US)",
pages = "1--9",
journal = "Acta Neuropsychiatrica",
issn = "0924-2708",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Clinically relevant and simple immune system measure is related to symptom burden in bipolar disorder

AU - Köhler-Forsberg, Ole

AU - Sylvia, Louisa

AU - Deckersbach, Thilo

AU - Ostacher, Michael Joshua

AU - McInnis, Melvin

AU - Iosifescu, Dan

AU - Bowden, Charles

AU - McElroy, Susan

AU - Calabrese, Joseph

AU - Thase, Michael

AU - Shelton, Richard Charles

AU - Tohen, Mauricio

AU - Kocsis, James

AU - Friedman, Edward

AU - Ketter, Terence

AU - Nierenberg, Andrew Alan

PY - 2017/12/7

Y1 - 2017/12/7

N2 - Objective: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. Methods: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. Results: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Conclusion: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

AB - Objective: Immunological theories, particularly the sickness syndrome theory, may explain psychopathology in mood disorders. However, no clinical trials have investigated the association between overall immune system markers with a wide range of specific symptoms including potential gender differences. Methods: We included two similar clinical trials, the lithium treatment moderate-dose use study and clinical and health outcomes initiatives in comparative effectiveness for bipolar disorder study, enrolling 765 participants with bipolar disorder. At study entry, white blood cell (WBC) count was measured and psychopathology assessed with the Montgomery and Aasberg depression rating scale (MADRS). We performed analysis of variance and linear regression analyses to investigate the relationship between the deviation from the median WBC, and multinomial regression analysis between different WBC levels. All analyses were performed gender-specific and adjusted for age, body mass index, smoking, race, and somatic diseases. Results: The overall MADRS score increased significantly for each 1.0×109/l deviation from the median WBC among 322 men (coefficient=1.10; 95% CI=0.32–1.89; p=0.006), but not among 443 women (coefficient=0.56; 95% CI=−0.19–1.31; p=0.14). Among men, WBC deviations were associated with increased severity of sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, inability to feel, and suicidal thoughts. Among women, WBC deviations were associated with increased severity of reduced appetite, concentration difficulties, lassitude, inability to feel, and pessimistic thoughts. Both higher and lower WBC levels were associated with increased severity of several specific symptoms. Conclusion: Immune system alterations were associated with increased severity of specific mood symptoms, particularly among men. Our results support the sickness syndrome theory, but furthermore emphasise the relevance to study immune suppression in bipolar disorder. Due to the explorative nature and cross-sectional design, future studies need to confirm these findings.

KW - affective disorder

KW - bipolar disorder

KW - clinical trials

KW - lithium

KW - mood stabilisers

KW - psychoneuroimmunology

UR - http://www.scopus.com/inward/record.url?scp=85038024403&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038024403&partnerID=8YFLogxK

U2 - 10.1017/neu.2017.34

DO - 10.1017/neu.2017.34

M3 - Article

AN - SCOPUS:85038024403

SP - 1

EP - 9

JO - Acta Neuropsychiatrica

JF - Acta Neuropsychiatrica

SN - 0924-2708

ER -