The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.
Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship
Abstract
About one-in-three breast cancer survivors have lingering cognitive complaints and objective cognitive impairment. Chronic inflammation and intestinal permeability (i.e., leaky gut), two risk factors for cognitive decline, can also fuel depression—another vulnerability for cognitive decline. The current study tested whether depression accompanied by high levels of inflammation or intestinal permeability predicted lower subjective and objective cognitive function in breast cancer survivors. We combined data from four breast cancer survivor studies (n = 613); some had repeated measurements for a total of 1015 study visits. All participants had a blood draw to obtain baseline measures of lipopolysaccharide binding protein—a measure of intestinal permeability, as well as three inflammatory markers that were incorporated into an inflammatory index: C-reactive protein, interleukin-6, and tumor necrosis factor-α. They reported depressive symptoms on the Center for Epidemiological Studies depression scale (CES-D), and a binary variable indicated clinically significant depressive symptoms (CES-D ≥ 16). The Kohli (749 observations) and the Breast Cancer Prevention Trial (591 observations) scales assessed subjective cognitive function. Objective cognitive function tests included the trail-making test, Hopkins verbal learning test, Conners continuous performance test, n-back test, FAS test, and animal-naming test (239–246 observations). Adjusting for education, age, BMI, cancer treatment type, time since treatment, study visit, and fatigue, women who had clinically elevated depressive symptoms accompanied by heightened inflammation or intestinal permeability reported poorer focus and marginally poorer memory. However, poorer performance across objective cognitive measures was not specific to inflammation-associated depression. Rather, there was some evidence of lower verbal fluency; poorer attention, verbal learning and memory, and working memory; and difficulties with visuospatial search among depressed survivors, regardless of inflammation. By themselves, inflammation and intestinal permeability less consistently predicted subjective or objective cognitive function. Breast cancer survivors with clinically significant depressive symptoms accompanied by either elevated inflammation or intestinal permeability may perceive greater cognitive difficulty, even though depression-related objective cognitive deficits may not be specific to inflammation- or leaky-gut-associated depression.
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Cognitive impairment in depression: a systematic review and meta-analysis
Rock, P. L., Roiser, J. P., Riedel, W. J., & Blackwell, A. D. (2014) · Psychological Medicine · doi:10.1017/s0033291713002535 · Cited by 2,161
Age differences in short-term retention of rapidly changing information.
Kirchner, W. K. (1958) · Journal of Experimental Psychology · doi:10.1037/h0043688 · Cited by 1,798
Cacioppo, J. T., Hawkley, L. C., & Thisted, R. A. (2010) · Psychology and Aging · doi:10.1037/a0017216 · Cited by 1,757
Working memory, attention control, and the N-back task: a question of construct validity
Kane, M. J., Conway, A. R. A., Miura, T. K., & Colflesh, G. J. H. (2007) · Journal of Experimental Psychology: Learning, Memory, and Cognition · doi:10.1037/0278-7393.33.3.615 · Cited by 933 · cited 1×
“The n-back test measures working memory [45].”
Osimo, E. F., Baxter, L. J., Lewis, G., Jones, P. B., & Khandaker, G. M. (2019) · Psychological Medicine · doi:10.1017/s0033291719001454 · Cited by 774 · cited 1×
“Clinically elevated inflammation accompanies at least 25% of depression cases [19], and the two may reciprocally reinforce one another [20]—a difficult-to-treat immune-mediated depression subtype.”
BackgroundWhat does plasma CRP tell us about peripheral and central inflammation in depression?
Felger, J. C., Haroon, E., Patel, T. A., Goldsmith, D. R., Wommack, E. C., Woolwine, B. J., Le, N.-A., Feinberg, R., Tansey, M. G., & Miller, A. H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-018-0096-3 · Cited by 448
How many different ways do patients meet the diagnostic criteria for major depressive disorder?
Zimmerman, M., Ellison, W., Young, D., Chelminski, I., & Dalrymple, K. (2015) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2014.09.007 · Cited by 392
Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.12.007 · Cited by 381 · cited 1×
“The typhoid vaccine can affect cognition [33], so only data from the placebo visit were used (162 study visits).”
MethodMac Giollabhui, N., Ng, T. H., Ellman, L. M., & Alloy, L. B. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-00867-4 · Cited by 361
Kiecolt-Glaser, J. K., Belury, M. A., Andridge, R., Malarkey, W. B., Hwang, B. S., & Glaser, R. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2012.05.011 · Cited by 233 · cited 2×
“For example, we found that one widely-available over-thecounter dietary supplement, omega-3 fatty acid, not only reduced basal inflammation [78] but also inflammatory responsivity to an acute stressor [79].”
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Research works printed but not linked: 67
- Joly, 2019, Long-Term Fatigue and Cognitive Disorders in Breast Cancer Survivors, Cancers, 11, 1896, 10.3390/cancers11121896 · DOI
- Dijkshoorn, 2021, Prevalence of Cognitive Impairment and Change in Patients with Breast Cancer: A Systematic Review of Longitudinal Studies, Psycho-Oncology, 30, 635, 10.1002/pon.5623 · DOI
- Bernstein, 2017, Cognitive Impairment in Breast Cancer Survivors Treated with Chemotherapy Depends on Control Group Type and Cognitive Domains Assessed: A Multilevel Meta-Analysis, Neurosci. Biobehav. Rev., 83, 417, 10.1016/j.neubiorev.2017.10.028 · DOI
- Whittaker, 2022, Prevalence of Cognitive Impairment Following Chemotherapy Treatment for Breast Cancer: A Systematic Review and Meta-Analysis, Sci. Rep., 12, 2135, 10.1038/s41598-022-05682-1 · DOI
- Boscher, C., Joly, F., Clarisse, B., Humbert, X., Grellard, J.-M., Binarelli, G., Tron, L., Licaj, I., and Lange, M. (2020). Perceived Cognitive Impairment in Breast Cancer Survivors and Its Relationships with Psychological Factors. Cancers, 12. · DOI
- Hutchinson, 2012, Objective and Subjective Cognitive Impairment Following Chemotherapy for Cancer: A Systematic Review, Cancer Treat. Rev., 38, 926, 10.1016/j.ctrv.2012.05.002 · DOI · Paper page
- Pullens, 2010, Subjective Cognitive Dysfunction in Breast Cancer Patients: A Systematic Review, Psycho-Oncology, 19, 1127, 10.1002/pon.1673 · DOI · Paper page
- Habermann, 2013, Impact of Perceived Cognitive Impairment in Breast Cancer Survivors, Eur. J. Oncol. Nurs., 17, 236, 10.1016/j.ejon.2012.06.002 · DOI · Paper page
- Savard, 2016, Subjective or Objective Measures of Cognitive Functioning—What’s More Important?, JAMA Oncol., 2, 1263, 10.1001/jamaoncol.2016.2047 · DOI
- Kohli, 2007, Self-Reported Cognitive Impairment in Patients with Cancer, J. Oncol. Pract., 3, 54, 10.1200/JOP.0722001 · DOI
- Tallman, 2015, Perceived Cognitive Function in Breast Cancer Survivors: Evaluating Relationships with Objective Cognitive Performance and Other Symptoms Using the Functional Assessment of Cancer Therapy—Cognitive Function Instrument, J. Pain Symptom Manag., 49, 697, 10.1016/j.jpainsymman.2014.08.012 · DOI
- Seliktar, 2015, Cognition in Breast Cancer Survivors: Hormones versus Depression, Psycho-Oncology, 24, 402, 10.1002/pon.3602 · DOI
- Jaremka, 2014, Cognitive Problems among Breast Cancer Survivors: Loneliness Enhances Risk, Psycho-Oncology, 23, 1356, 10.1002/pon.3544 · DOI
- American Psychiatric Association, D., and American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders: DSM-5, American Psychiatric Association. · DOI · Paper page
- Chang, 2012, Treatment Response and Cognitive Impairment in Major Depression: Association with C-Reactive Protein, Brain Behav. Immun., 26, 90, 10.1016/j.bbi.2011.07.239 · DOI · Paper page
- Carlier, 2021, Inflammation and Cognitive Functioning in Depressed Older Adults Treated with Electroconvulsive Therapy: A Prospective Cohort Study, J. Clin. Psychiatry, 82, 35808, 10.4088/JCP.20m13631 · DOI
- Krogh, 2014, The Association between Depressive Symptoms, Cognitive Function, and Inflammation in Major Depression, Brain Behav. Immun., 35, 70, 10.1016/j.bbi.2013.08.014 · DOI
- Carroll, 2023, Elevated C-Reactive Protein and Subsequent Patient-Reported Cognitive Problems in Older Breast Cancer Survivors: The Thinking and Living with Cancer Study, J. Clin. Oncol., 41, 295, 10.1200/JCO.22.00406 · DOI · Paper page
- Camilleri, 2019, Leaky Gut: Mechanisms, Measurement and Clinical Implications in Humans, Gut, 68, 1516, 10.1136/gutjnl-2019-318427 · DOI · Paper page
- Madison, 2020, Endotoxemia Coupled with Heightened Inflammation Predicts Future Depressive Symptoms, Psychoneuroendocrinology, 122, 104864, 10.1016/j.psyneuen.2020.104864 · DOI
- Madison, 2020, Afternoon Distraction: A High-Saturated-Fat Meal and Endotoxemia Impact Postmeal Attention in a Randomized Crossover Trial, Am. J. Clin. Nutr., 111, 1150, 10.1093/ajcn/nqaa085 · DOI
- Blasco, 2017, Neuroinflammation in Obesity: Circulating Lipopolysaccharide-Binding Protein Associates with Brain Structure and Cognitive Performance, Int. J. Obes., 41, 1627, 10.1038/ijo.2017.162 · DOI
- Bennett, 2014, Yoga’s Impact on Inflammation, Mood, and Fatigue in Breast Cancer Survivors: A Randomized Controlled Trial, J. Clin. Oncol., 32, 1040, 10.1200/JCO.2013.51.8860 · DOI · Paper page
- Renna, 2022, Breast Cancer Survivors’ Vaccine Responses: Chemotherapy, Obesity, and Fitness Make a Difference, Brain Behav. Immun., 103, 1, 10.1016/j.bbi.2022.03.019 · DOI
- Madison, A.A., Filatov, M., Andridge, R., Haas, G., Povoski, S.P., Agnese, D.M., Lustberg, M., Reinbolt, R.E., Wesolowski, R., and Williams, N.O. (2023). A Troubled Heart: Mood Disorder History Longitudinally Predicts Faster Cardiopulmonary Aging in Breast Cancer Survivorship. PLoS ONE, 18. · DOI
- Terhorst, 2011, Evaluation of the Psychometric Properties of the BCPT Symptom Checklist with a Sample of Breast Cancer Patients before and after Adjuvant Therapy, Psycho-Oncology, 20, 961, 10.1002/pon.1806 · DOI
- Lin, 2021, Trail Making Test Performance Using a Touch-Sensitive Tablet: Behavioral Kinematics and Electroencephalography, Front. Hum. Neurosci., 15, 663463, 10.3389/fnhum.2021.663463 · DOI
- Kortte, 2002, The Trail Making Test, Part B: Cognitive Flexibility or Ability to Maintain Set?, Appl. Neuropsychol., 9, 106, 10.1207/S15324826AN0902_5 · DOI · Paper page
- Small, 2012, The Diagnostic Value of Controlled Oral Word Association Test-FAS and Category Fluency in Single-Domain Amnestic Mild Cognitive Impairment, Dement. Geriatr. Cogn. Disord., 32, 235
- Campagna, 2017, The Animal Naming Test: An Easy Tool for the Assessment of Hepatic Encephalopathy, Hepatology, 66, 198, 10.1002/hep.29146 · DOI
- Conners, C.K. (2014). Conners Continuous Performance Test 3rd Edition (Conners CPT 3) & Connors Continuous Auditory Test of Attention (Conners CATA): Technical Manual, MHS.
- Scimeca, 2021, Examining Conners Continuous Performance Test-3 (CPT-3) Embedded Performance Validity Indicators in an Adult Clinical Sample Referred for ADHD Evaluation, Dev. Neuropsychol., 46, 347, 10.1080/87565641.2021.1951270 · DOI
- Rabin, 2005, Assessment Practices of Clinical Neuropsychologists in the United States and Canada: A Survey of INS, NAN, and APA Division 40 Members, Arch. Clin. Neuropsychol., 20, 33, 10.1016/j.acn.2004.02.005 · DOI · Paper page
- Benedict, 1998, Hopkins Verbal Learning Test–Revised: Normative Data and Analysis of Inter-Form and Test-Retest Reliability, Clin. Neuropsychol., 12, 43, 10.1076/clin.12.1.43.1726 · DOI · Paper page
- Chiaravalloti, 2005, Treating Learning Impairments Improves Memory Performance in Multiple Sclerosis: A Randomized Clinical Trial, Mult. Scler. J., 11, 58, 10.1191/1352458505ms1118oa · DOI
- Radloff, 1977, The CES-D Scale: A Self-Report Depression Scale for Research in the General Population, Appl. Psychol. Meas., 1, 385, 10.1177/014662167700100306 · DOI · Paper page
- Weissman, 1977, Assessing Depressive Symptoms in Five Psychiatric Populations: A Validation Study, Am. J. Epidemiol., 106, 203, 10.1093/oxfordjournals.aje.a112455 · DOI · Paper page
- Fontes, 2013, Clinical Correlates of Change in Inflammatory Biomarkers: The Framingham Heart Study, Atherosclerosis, 228, 217, 10.1016/j.atherosclerosis.2013.01.019 · DOI
- Kell, 2015, On the Translocation of Bacteria and Their Lipopolysaccharides between Blood and Peripheral Locations in Chronic, Inflammatory Diseases: The Central Roles of LPS and LPS-Induced Cell Death, Integr. Biol., 7, 1339, 10.1039/c5ib00158g · DOI
- Brenchley, 2006, Microbial Translocation Is a Cause of Systemic Immune Activation in Chronic HIV Infection, Nat. Med., 12, 1365, 10.1038/nm1511 · DOI · Paper page
- Gonzalez-Quintela, A., Alonso, M., Campos, J., Vizcaino, L., Loidi, L., and Gude, F. (2013). Determinants of Serum Concentrations of Lipopolysaccharide-Binding Protein (LBP) in the Adult Population: The Role of Obesity. PLoS ONE, 8. · DOI
- Vallejo, 2013, Correlation Between Different Methods to Measure Microbial Translocation and Its Association with Immune Activation in Long-Term Suppressed HIV-1–Infected Individuals, JAIDS J. Acquir. Immune Defic. Syndr., 64, 149, 10.1097/QAI.0b013e31829a2f12 · DOI
- Uhde, 2016, Intestinal Cell Damage and Systemic Immune Activation in Individuals Reporting Sensitivity to Wheat in the Absence of Coeliac Disease, Gut, 65, 1930, 10.1136/gutjnl-2016-311964 · DOI
- Tremellen, 2020, Small Intestinal Bacterial Overgrowth (SIBO) as a Potential Cause of Impaired Spermatogenesis, Gut, 69, 2058, 10.1136/gutjnl-2020-320766 · DOI
- Lakatos, 2010, Serum Lipopolysaccharide-Binding Protein and Soluble CD14 Are Markers of Disease Activity in Patients with Crohn’s Disease, Inflamm. Bowel Dis., 17, 767, 10.1002/ibd.21402 · DOI
- Sanderman, 1996, Psychometric Qualities of the RAND 36-Item Health Survey 1.0: A Multidimensional Measure of General Health Status, Int. J. Behav. Med., 3, 104, 10.1207/s15327558ijbm0302_2 · DOI · Paper page
- Walker, 2019, Systemic Inflammation during Midlife and Cognitive Change over 20 Years: The ARIC Study, Neurology, 92, e1256, 10.1212/WNL.0000000000007094 · DOI · Paper page
- Ellman, 2020, To Exclude or Not to Exclude: Considerations and Recommendations for C-Reactive Protein Values Higher than 10 Mg/L, Brain Behav. Immun., 87, 898, 10.1016/j.bbi.2020.01.023 · DOI
- Ballinger, 2004, Using Generalized Estimating Equations for Longitudinal Data Analysis, Organ. Res. Methods, 7, 127, 10.1177/1094428104263672 · DOI · Paper page
- Zeger, 1986, Longitudinal Data Analysis for Discrete and Continuous Outcomes, Biometrics, 42, 121, 10.2307/2531248 · DOI · Paper page
- Capuron, 2002, Neurobehavioral Effects of Interferon-α in Cancer Patients: Phenomenology and Paroxetine Responsiveness of Symptom Dimensions, Neuropsychopharmacology, 26, 643, 10.1016/S0893-133X(01)00407-9 · DOI · Paper page
- Sundermann, 2017, Does the Female Advantage in Verbal Memory Contribute to Underestimating Alzheimer’s Disease Pathology in Women versus Men?, J. Alzheimer’s Dis., 56, 947, 10.3233/JAD-160716 · DOI
- Oliver, 2022, Subjective Cognitive Decline Is a Better Marker for Future Cognitive Decline in Females than in Males, Alzheimer’s Res. Ther., 14, 197, 10.1186/s13195-022-01138-w · DOI
- Ahmadi, 2020, Metformin Reduces Aging-Related Leaky Gut and Improves Cognitive Function by Beneficially Modulating Gut Microbiome/Goblet Cell/Mucin Axis, J. Gerontol. Ser. A, 75, e9, 10.1093/gerona/glaa056 · DOI
- Ryan, 2001, Plasma Levels of Soluble CD14 and Tumor Necrosis Factor-α Type II Receptor Correlate with Cognitive Dysfunction during Human Immunodeficiency Virus Type 1 Infection, J. Infect. Dis., 184, 699, 10.1086/323036 · DOI
- Lyons, 2011, Plasma SCD14 Is a Biomarker Associated with Impaired Neurocognitive Test Performance in Attention and Learning Domains in HIV Infection, J. Acquir. Immune Defic. Syndr., 57, 371, 10.1097/QAI.0b013e3182237e54 · DOI
- Rundek, 2021, Gut Permeability and Cognitive Decline: A Pilot Investigation in the Northern Manhattan Study, Brain Behav. Immun.-Health, 12, 100214, 10.1016/j.bbih.2021.100214 · DOI
- Ufnal, 2017, The Gut-Blood Barrier Permeability—A New Marker in Cardiovascular and Metabolic Diseases?, Med. Hypotheses, 98, 35, 10.1016/j.mehy.2016.11.012 · DOI
- Zanoli, 2020, Vascular Consequences of Inflammation: A Position Statement from the ESH Working Group on Vascular Structure and Function and the ARTERY Society, J. Hypertens., 38, 1682, 10.1097/HJH.0000000000002508 · DOI
- Bradshaw, 2016, Cardiovascular Disease Mortality among Breast Cancer Survivors, Epidemiology, 27, 6, 10.1097/EDE.0000000000000394 · DOI · Paper page
- McAfoose, 2009, Evidence for a Cytokine Model of Cognitive Function, Neurosci. Biobehav. Rev., 33, 355, 10.1016/j.neubiorev.2008.10.005 · DOI · Paper page
- Turkheimer, 2023, Sickness Behaviour and Depression: An Updated Model of Peripheral-Central Immunity Interactions, Brain Behav. Immun., 111, 202, 10.1016/j.bbi.2023.03.031 · DOI
- Derry, 2015, Sex Differences in Depression: Does Inflammation Play a Role?, Curr. Psychiatry Rep., 17, 78, 10.1007/s11920-015-0618-5 · DOI
- Wang, 2020, Sex Differences in the Cognitive Function of First-Diagnosed, Drug-Naïve Depressed Patients: An Observational Case-Control Study, J. Affect. Disord., 276, 461, 10.1016/j.jad.2020.07.114 · DOI
- Madison, 2021, Omega-3 Supplementation and Stress Reactivity of Cellular Aging Biomarkers: An Ancillary Substudy of a Randomized, Controlled Trial in Midlife Adults, Mol. Psychiatry, 26, 3034, 10.1038/s41380-021-01077-2 · DOI
- Kaliannan, 2015, A Host-Microbiome Interaction Mediates the Opposing Effects of Omega-6 and Omega-3 Fatty Acids on Metabolic Endotoxemia, Sci. Rep., 5, 11276, 10.1038/srep11276 · DOI · Paper page
- Barnes, 2021, Omega-3 Fatty Acids Are Associated with Blood–Brain Barrier Integrity in a Healthy Aging Population, Brain Behav., 11, e2273, 10.1002/brb3.2273 · DOI · Paper page
Metadata
- Authors
- Madison, A. A., Andridge, R., Kantaras, A. H., Renna, M. E., Bennett, J. M., Alfano, C. M., Povoski, S. P., Agnese, D. M., Lustberg, M., Wesolowski, R., Carson, W. E., Williams, N. O., Reinbolt, R. E., Sardesai, S. D., Noonan, A. M., Stover, D. G., Cherian, M. A., Malarkey, W. B., & Kiecolt-Glaser, J. K.
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2023-09-04
- Volume
- 15
- Issue
- 17
- Pages
- 4414
- ISSN
- 2072-6694
- Cited by
- 14
- References
- 14
- Language
- en
- Funders
- NIH (R01 CA126857, R01 CA131029, R01 CA186251, R01CA186720, K05 CA172296, UL1RR025755, UL1TR002733, UL1TR001070, CA016058)
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- Madison, A. A., Andridge, R., Kantaras, A. H., Renna, M. E., Bennett, J. M., Alfano, C. M., Povoski, S. P., Agnese, D. M., Lustberg, M., Wesolowski, R., Carson, W. E., Williams, N. O., Reinbolt, R. E., Sardesai, S. D., Noonan, A. M., Stover, D. G., Cherian, M. A., Malarkey, W. B., & Kiecolt-Glaser, J. K. (2023). Depression, Inflammation, and Intestinal Permeability: Associations with Subjective and Objective Cognitive Functioning throughout Breast Cancer Survivorship. Cancers. https://doi.org/10.3390/cancers15174414
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