White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder
Open accessAbstract
Objective: Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown. Methods: The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between deviations from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia. Results: Among 482 Bipolar CHOICE participants, for each 1.0 × 10 9 /L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient = 2.13; 95% confidence interval = [0.46, −3.79]; p = 0.013), but not among women (coefficient = 0.87; 95% confidence interval = [−0.87, −2.61]; p = 0.33). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient = 1.51; 95% confidence interval = [−0.81, −3.82]; p = 0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient = 1.33; 95% confidence interval = [−0.22, −2.89]; p = 0.09), but not among women (coefficient = 0.34; 95% confidence interval = [−0.64, −1.32]; p = 0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg Depression Rating Scale scores increased significantly among men (coefficient = 1.09; 95% confidence interval = [0.31, −1.87]; p = 0.006) for each 1.0 × 10 9 /L white blood cell deviation, whereas we found a weak association among women (coefficient = 0.55; 95% confidence interval = [−0.20, −1.29]; p = 0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender. Conclusion: Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139 · see citing works
A new depression scale designed to be sensitive to change
Montgomery, S. A., & Åsberg, M. (1979) · British Journal of Psychiatry · doi:10.1192/bjp.134.4.382 · Cited by 13,962 · see citing works
Journal of Clinical Psychiatry
(2018) · Journal of Clinical Psychiatry · doi:10.5505/kpd · Cited by 13,703 · see citing works
A Rating Scale for Mania: Reliability, Validity and Sensitivity
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978) · British Journal of Psychiatry · doi:10.1192/bjp.133.5.429 · Cited by 8,744 · see citing works
Raison, C. L., Rutherford, R. E., Woolwine, B. J., Shuo, C., Schettler, P., Drake, D. F., Haroon, E., & Miller, A. H. (2013) · JAMA Psychiatry · doi:10.1001/2013.jamapsychiatry.4 · Cited by 1,617 · see citing works
The Relationship of Depression and Stressors to Immunological Assays: A Meta-Analytic Review
Zorrilla, E. P., Luborsky, L., McKay, J. R., Rosenthal, R., Houldin, A., Tax, A., McCorkle, R., Seligman, D. A., & Schmidt, K. (2001) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2000.0597 · Cited by 995 · see citing works
Spearing, M. K., Post, R. M., Leverich, G. S., Brandt, D., & Nolen, W. (1997) · Psychiatry Research · doi:10.1016/s0165-1781(97)00123-6 · Cited by 978 · see citing works
Which White Blood Cell Subtypes Predict Increased Cardiovascular Risk?
Horne, B. D., Anderson, J. L., John, J. M., Weaver, A. N., Bair, T. L., Jensen, K. R., Renlund, D. G., & Muhlestein, J. B. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.02.054 · Cited by 967 · see citing works
Köhler, O., Benros, M. E., Nordentoft, M., Farkouh, M. E., Iyengar, R. L., Mors, O., & Krogh, J. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1611 · Cited by 941 · see citing works
Antipsychotic medication in schizophrenia: a review
Lally, J., & MacCabe, J. H. (2015) · British Medical Bulletin · doi:10.1093/bmb/ldv017 · Cited by 515 · see citing works
White blood cell count and cardiovascular disease. Insights from the Framingham Study
Kannel, W. B. (1992) · JAMA · doi:10.1001/jama.267.9.1253 · Cited by 366 · see citing works
Angele, M. K., Pratschke, S., Hubbard, W. J., & Chaudry, I. H. (2013) · Virulence · doi:10.4161/viru.26982 · Cited by 345 · see citing works
Drexhage, R. C., Knijff, E. M., Padmos, R. C., Heul-Nieuwenhuijzen, L. V. D., Beumer, W., Versnel, M. A., & Drexhage, H. A. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.09.144 · Cited by 263 · see citing works
White Blood Cell Count and Cardiovascular Disease
Kannel, W. B. (1992) · JAMA · doi:10.1001/jama.1992.03480090101035 · Cited by 258 · see citing works
How Do Immune Cells Support and Shape the Brain in Health, Disease, and Aging?
Schwartz, M., Kipnis, J., Rivest, S., & Prat, A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3241-13.2013 · Cited by 256 · see citing works
Krogh, J., Benros, M. E., Jørgensen, M. B., Vesterager, L., Elfving, B., & Nordentoft, M. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.08.014 · Cited by 185 · see citing works
Hope, S., Dieset, I., Agartz, I., Steen, N. E., Ueland, T., Melle, I., Aukrust, P., & Andreassen, O. A. (2011) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2011.08.003 · Cited by 164 · cited 5× · see citing works
“…as C-reactive protein (CRP) or interleukin-1 receptor antagonist (IL-1ra), are associated with bipolar disorder severity (Hope et al., 2013) and symptom-clusters, including affective (Hope et al., 2011), psychotic (Hope et al., 2013) and cognitive (Hope et al., 2015; Lotrich et al., 2014) profiles.”
BackgroundResultInfluentialVieta, E., T'joen, C., McQuade, R. D., Carson, W. H., Marcus, R. N., Sanchez, R., Owen, R., & Nameche, L. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07101560 · Cited by 160 · see citing works
C-Reactive Protein Alterations in Bipolar Disorder: A Meta-Analysis
Dargél, A. A., Godin, O., Kapczinski, F., Kupfer, D. J., & Leboyer, M. (2015) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.14r09007 · Cited by 155 · cited 3× · see citing works
“Australian & New Zealand Journal of Psychiatry, 51(4) The immune system and bipolar disorder symptom severity States of immune system activation represent frequent findings among bipolar disorder patients compared to healthy controls (Bai et al., 2014; Dargel et al., 2015; Drexhage et al., 2010).”
BackgroundBowden, C. L., Vieta, E., Ice, K. S., Schwartz, J. H., Wang, P. P., & Versavel, M. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05482yel · Cited by 144 · see citing works
Self-citationHope, S., Ueland, T., Steen, N. E., Dieset, I., Lorentzen, S., Berg, A. O., Agartz, I., Aukrust, P., & Andreassen, O. A. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2012.12.023 · Cited by 131 · see citing works
Bai, Y., Su, T., Tsai, S., Chiou, W., Li, C., Tu, P., & Mu-Hong, C. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.05.009 · Cited by 117 · see citing works
Hope, S., Hoseth, E. Z., Dieset, I., Mørch, R. H., Aas, M., Aukrust, P., Djurovic, S., Melle, I. S., Ueland, T., Agartz, I., et al. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.04.004 · Cited by 114 · see citing works
Arabzadeh, S., Ameli, N., Zeinoddini, A., Rezaei, F., Farokhnia, M., Mohammadinejad, P., Ghaleiha, A., & Akhondzadeh, S. (2015) · Bipolar Disorders · doi:10.1111/bdi.12324 · Cited by 100 · see citing works
Development of the Bipolar Inventory of Symptoms Scale
Bowden, C. L., Singh, V., Thompson, P., Gonzalez, J. M., Katz, M. M., Dahl, M., Prihoda, T. J., & Chang, X. (2006) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2006.00955.x · Cited by 94 · see citing works
Self-citation‘As above, so below’ examining the interplay between emotion and the immune system
Brod, S., Rattazzi, L., Piras, G., & D’Acquisto, F. (2014) · Immunology · doi:10.1111/imm.12341 · Cited by 86 · see citing works
Soreca, I., Fagiolini, A. M., Frank, E., Houck, P. R., Thompson, W. K., & Kupfer, D. J. (2008) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2007.10.009 · Cited by 86 · see citing works
Liu, B., & Taioli, E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142382 · Cited by 86 · see citing works
Goldstein, B. I., & Young, L. T. (2013) · Current Psychiatry Reports · doi:10.1007/s11920-013-0425-9 · Cited by 84 · see citing works
Lotrich, F. E., Butters, M. A., Aizenstein, H. J., Marron, M. M., Reynolds, C. F., & Gildengers, A. G. (2013) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4048 · Cited by 83 · see citing works
Nierenberg, A. A., Sylvia, L. G., Leon, A. C., Reilly-Harrington, N. A., Shesler, L. W., McElroy, S. L., Friedman, E. S., Thase, M. E., Shelton, R. C., Bowden, C. L., et al. (2013) · Clinical Trials · doi:10.1177/1740774513512184 · Cited by 73 · see citing works
Self-citationLi, H., Hong, W., Zhang, C., Wu, Z., Wang, Z., Yuan, C., Li, Z., Huang, J., Lin, Z., & Fang, Y. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.12.033 · Cited by 63 · see citing works
Walker, A. J., Kim, Y., Price, J. B., Kale, R. P., McGillivray, J., Berk, M., & Tye, S. J. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00034 · Cited by 63 · see citing works
Rocha, N. P., Teixeira, A. L., Scalzo, P. L., Barbosa, I. G., de Sousa, M. S., Morato, I. B., Vieira, É. L. M., Christo, P. P., Palotás, A., & Reis, H. J. (2013) · Movement Disorders · doi:10.1002/mds.25752 · Cited by 61 · see citing works
Rabkin, J. G., Wagner, G. J., & Rabkin, R. (1994) · PubMed · Cited by 58 · see citing works
Gonzalez, J. M., Bowden, C. L., Katz, M. M., Thompson, P., Singh, V. K., Prihoda, T. J., & Dahl, M. (2008) · International Journal of Methods in Psychiatric Research · doi:10.1002/mpr.262 · Cited by 54 · see citing works
Self-citationAyorech, Z., Tracy, D. K., Baumeister, D., & Giaroli, G. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.12.015 · Cited by 53 · see citing works
T cells in the central nervous system: messengers of destruction or purveyors of protection?
Walsh, J. T., Watson, N., & Kipnis, J. (2014) · Immunology · doi:10.1111/imm.12187 · Cited by 52 · see citing works
Lithium treatment — moderate dose use study (LiTMUS) for bipolar disorder: rationale and design
Nierenberg, A. A., Sylvia, L. G., Leon, A. C., Reilly-Harrington, N. A., Ketter, T. A., Calabrese, J. R., Thase, M. E., Bowden, C. L., Friedman, E. S., Ostacher, M. J., et al. (2009) · Clinical Trials · doi:10.1177/1740774509347399 · Cited by 45 · see citing works
Self-citationThompson, P. M., Gonzalez, J. M., Singh, V. K., Schoolfield, J. D., Katz, M. M., & Bowden, C. L. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2009.04.017 · Cited by 36 · see citing works
Self-citationPsychological factors and survival after bone marrow transplantation in patients with leukemia
Akaho, R., Sasaki, T., Mori, S., et al. (2003) · Psychiatry and Clinical Neurosciences · doi:10.1046/j.1440-1819.2003.01084.x · Cited by 32 · see citing works
Laske, C., Schmohl, M., Leyhe, T., Stransky, E., Maetzler, W., Berg, D., Fallgatter, A. J., Joos, T. O., & Dietzsch, J. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121558 · Cited by 22 · see citing works
Amitai, M., Zivony, A., Kronenberg, S., Nagar, L., Saar, S., Sever, J. M., Apter, A., Shoval, G., Golubchik, P., Hermesh, H., et al. (2014) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2013.0046 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Köhler-Forsberg, O., Buttenschøn, H. N., Tansey, K. E., Maier, W., Hauser, J., Dernovsek, M. Z., Henigsberg, N., Souery, D., Farmer, A., Rietschel, M., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.02.020 · Cited by 283 · see citing works
Kofod, J., Elfving, B., Nielsen, E. H., Mors, O., & Köhler-Forsberg, O. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2021.09.006 · Cited by 136 · see citing works
Osimo, E. F., Cardinal, R. N., Jones, P. B., & Khandaker, G. M. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.02.031 · Cited by 124 · see citing works
Dadouli, K., Janho, M. B., Hatziefthimiou, A., Voulgaridi, I., Piaha, K., Anagnostopoulos, L., Ntellas, P., Mouchtouri, V. A., Bonotis, K., Christodoulou, N., et al. (2022) · Brain Sciences · doi:10.3390/brainsci12081034 · Cited by 57 · see citing works
Do Statins Have Antidepressant Effects?
Köhler-Forsberg, O., Gasse, C., Berk, M., & Østergaard, S. D. (2017) · CNS Drugs · doi:10.1007/s40263-017-0422-3 · Cited by 31 · see citing works
Gan, Z., Wu, X., Liao, Y., Wu, Y., He, Z., Yang, Z., & Zhang, Q. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.12.239 · Cited by 20 · see citing works
Köhler-Forsberg, O., Sylvia, L., Deckersbach, T., Ostacher, M. J., McInnis, M., Iosifescu, D., Bowden, C., McElroy, S., Calabrese, J., Thase, M., et al. (2018) · Acta Neuropsychiatrica · doi:10.1017/neu.2017.34 · Cited by 15 · see citing works
Self-citation
- Authors
- Köhler, O., Sylvia, L. G., Bowden, C. L., Calabrese, J. R., Thase, M., Shelton, R. C., McInnis, M., Tohen, M., Kocsis, J. H., Ketter, T. A., Friedman, E. S., Deckersbach, T., Ostacher, M. J., Iosifescu, D. V., McElroy, S., & Nierenberg, A. A.
- Affiliations
- Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark
- Harvard University (US)
- The University of Texas at San Antonio Health Science Center (US)
- Case Western Reserve University (US)
- University of Pennsylvania (US)
- University of Alabama at Birmingham (US)
- University of Michigan (US)
- University of New Mexico (US)
- Weill Cornell Medicine (US)
- Stanford Medicine (US)
- University of Pittsburgh Medical Center (US)
- VA Palo Alto Health Care System (US)
- Icahn School of Medicine at Mount Sinai (US)
- Lindner Center of HOPE (US)
- ORCID
- Venue
- Australian & New Zealand Journal of Psychiatry
- Publisher
- SAGE Publications
- Published
- 2016-07-11
- Volume
- 51
- Issue
- 4
- Pages
- 355-365
- ISSN
- 0004-8674 (ISSN-L)
- 1440-1614
- OpenAlex
- W2343312844
- Cited by
- 33
- References
- 43
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 5
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Australian & New Zealand Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Agency for Healthcare Research and Quality (1R01HS019371, 1r01hs019371-01)
- National Institute of Mental Health (NO1MH80001)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- bipolar disorder, white blood cell count, immune system alterations, sex differences, depression, lithium therapy, LITMUS, mood symptoms, mood stabilizers, comparative effectiveness trials
- MeSH terms
- Adolescent, Adult, Affect, Bipolar Disorder, Female, Humans, Immune System, Leukocyte Count, Lithium, Male, Middle Aged, Psychiatric Status Rating Scales, Severity of Illness Index, Sex Characteristics, United States, Linear Models, Logistic Models, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
