Open Access Open Access  Restricted Access Subscription or Fee Access

Associations of biological stress markers in hurricane survivors: Heartrate variability, Interleukin-2 and Interleukin-6 in depression and PTSD

Phebe Tucker, MD, Betty Pfefferbaum, MD, JD, Yan D. Zhao, PhD, Sarah E. Johnston, MS, Amit Mistry, MD, PGY-4, Qaiser S. Khan, MD, MPH

Abstract


Objective: Inflammatory and immunologic cytokines and vagal activity have important roles in health and mental health, and may influence each other. The authors assessed relationships of representative biomarkers linked to disaster exposure—heart rate variability (HRV) with Interleukin-2 (IL-2, cell-medicated immunity) and Interleukin-6 (IL-6, proinflammatory and pro-immunologic), stratified by psychiatric diagnosis.

Design: Participants were assessed for psychiatric diagnosis, IL-2, IL-6, HRV, and HR reactivity to trauma reminders.

Setting: Outpatient university psychiatry clinics in Oklahoma City and Tulsa.

Participants: Relocated Katrina survivors and demographically matched controls, not on psychiatric, cardiovascular, or inflammatory medications.

Main outcome measures: SCID-IV, baseline serum IL-2 and IL-6, HRV through power spectral analysis.

Results: Survivors had higher sympathetic and lower parasympathetic activity at baseline and lower parasympathetic HR reactivity than controls, with flattened parasympathetic reactivity in the presence of depression and of post-traumatic stress disorder (PTSD). Survivors’ IL-2 and IL-6 did not differ from controls and did not differ in PTSD or depression. Depressed survivors’ sympathetic reactivity correlated negatively with IL-2 and parasympathetic reactivity correlated positively with IL-2.

Conclusions: HRV differed after hurricane exposure and with survivors’ depression and/or PTSD, more sensitively capturing somatic sequelae than assessed cytokines. Higher sympathetic HR reactivity associated with lower immunologic IL-2 may indicate a double biological “hit” in depressed disaster survivors, possibly rendering them more vulnerable to cardiovascular and immunologic illness as well as depression. Associations of HRV with IL-2 may support reciprocal influences of cytokines and vagal activity. Lack of significant correlations of IL-6 with HRV measures is consistent with its pleiotropic role.


Keywords


heart rate variability, Interleukin-2, Interleukin-6, cytokines, depression, PTSD, Hurricane Katrina, inflammation, immune, biological stress Markers

Full Text:

PDF

References


Baker D, Nievergelt CM, O’Connor DT: Biomarkers of PTSD: Neuropeptides and immune signaling. Neuropharmacology. 2012; 72: 663-673.

Colvonen PJ, Glassman LH, Drocker LD, et al.: Pretreatment biomarkers predicting PTSD psychotherapy outcomes: A systematic review. Neurosci Biobehav Rev. 2017; 75: 140-156.

Tucker P, Ruwe WD, Masters BK, et al.: Neuroimmune and cortisol

changes in SSRI and placebo treatment of chronic PTSD. Biol Psychiatry. 2004; 56(2): 121-128.

Yehuda R, Flory JD, Bierer LM, et al.: Lower methylation of glucocorticoid receptor gene promotor IF in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry. 2015; 77: 356-364.

Passos LC, Vasconcelos-Moreno MP, Costa LG, et al.: Inflammatory markers in post-traumatic stress disorder: A systematic review, meta-analysis, and meta-regression. Lancet Psychiatry. 2015; 2: 1002-1012.

Walker FR, Pfingst K, Carnevali L, et al.: In the search for integrative biomarker of resilience to psychological stress. Neurosci Biobehav Rev. 2017; 74: 310-320.

Aiello AE, Dowd JB, Jayabalasingham B, et al.: PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit. Psychoneuroendocrinology. 2016; 67: 133-141.

Yehuda R, Hoge CW, McFarlane AC, et al.: Post-traumatic stress disorder. Nat Rev Dis Primers. 2015; 1: 150-157.

Song Y, Zhou D, Guan Z, et al.: Disturbance of serum interleukin-2 and interleukin-8 levels in posttraumatic and non-posttraumatic stress disorder earthquake survivors in northern China. Neuroimmunomodulation. 2017; 14: 248-254.

Nunes SO, Reiche EM, Morimoto HK, et al.: Immune and hormonal activity in adults suffering from depression. Braz J Med Biol Res. 2002; 35(5): 581-587.

Miller BJ, Buckley P, Seabolt W, et al.: Meta-analysis of cytokine alterations in schizophrenia: Clinical status and antipsychotic effects. Biol Psychiatry. 2011; 70: 663-671.

Tucker P, Pfefferbaum B, Nitiema P, et al.: Inflammatory and immunologic interleukins linked with psychiatric diagnosis, disaster and ethnicity. Cytokine. 2017; 96: 247-252.

Scheller JI, Chalaris A, Schmidt-Arras D, et al.: The pro- and anti-inflammatory properties of the cytokine interleukin-6. Biochim Biophys Acta. 2011; 1813(5): 878-888.

Hunter CA, Jones SA: IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015; 16(5): 448-455.

Tucker P, Jeon-Slaughter H, Pfefferbaum B, et al.: Emotional and biological stress measures in Katrina survivors relocated to Oklahoma. Am J Disaster Med. 2010; 5(2): 113-125.

Plantings L, Bremner JD, Miller AH, et al.: Association between posttraumatic stress disorder and inflammation: A twin study. Brain Behav Immun. 2013; 30: 125-132.

Suareza EC: Joint effect of hostility and severity of depressive symptoms on plasma Interleukin-6 concentration. Psychosom Med. 2003; 65(4): 523-527.

Spooren A, Krzysztof K, Laureys G, et al.: Interleukin-6, a mental cytokine. Brain Res Rev. 2011; 67: 157-183.

Stein PK, Carney RM, Freedland KE, et al.: Severe depression is associated with markedly reduced heart rate variability in patients with stable coronary heart disease. J Psychosom Res. 2000; 48: 493-500.

Tucker P, Pfefferbaum B, Jeon-Slaughter H, et al.: Emotional stress and heart rate variability measures associated with cardiovascular risk in relocated Katrina survivors. Psychosom Med. 2012(74): 160-168.

Cohen H, Benjamin J, Geva AB, et al.: Autonomic dysregulation in panic disorder and in post-traumatic stress disorder: Application of power spectrum analysis of heart rate variability at rest and in response to recollection of trauma or panic attacks. Psychiatry Res. 2000; (25):1-13.

Lin LY, Wu CC, Liu YB, et al.: Derangement of heart rate variability during a catastrophic earthquake: A possible mechanism for increased heart attacks. Pacing Clin Electrophysiol. 2001; 24: 1596-1601.

Morris MC, Hellman N, Abelson JL, et al.: Cortisol, heart rate and blood pressure as early markers of PTSD risk: A systematic review and meta-analysis. Clin Psychol Rev. 2016; 49: 79-91.

Green KT, Dennis PA, Neal LC, et al.: Exploring the relationship between posttraumatic stress disorder symptoms and momentary heart rate variability. J Psychosom Res. 2016; 82: 31-34.

Dennis PA, Dedert EA, Van Voorhees EE, et al.: Examining the crux of autonomic dysfunction in posttraumatic stress disorder: Whether chronic or situational distress underlies elevated heart rate and attenuated heart rate variability. Psychosom Med. 2016; 78: 805-809.

Tucker P, Beebe KL, Burgin C, et al.: Paroxetine treatment of depression with PTSD: Effects on autonomic reactivity and cortisol secretion. J Clin Psychopharm. 2004; 24(2): 131-140.

Cooper TM, McKinley PS, Seeman TE, et al: Heart rate variability predicts levels of inflammatory markers: Evidence for the vagal anti-inflammatory pathway. Brain Behav Immun. 2015; 49: 94-100.

Myint AM: Kynurenines: From the perspective of major psychiatric disorders. FEBS J. 2012; 279: 1375-1385.

Vollmer-Conna U, Cvejic E, Smith IG, et al.: Characterizing acute coronary syndrome-associated depression: Let the data speak. Brain Behav Immun. 2015; 48: 19-28.

Harrison NA, Cooper E, Voon V, et al.: Central autonomic network mediates cardiovascular responses to acute inflammation: Relevance to increased cardiovascular risk in depression? Brain Behav Immun. 2013; 31: 189-196.

First MB, Spitzer RL, Gibbon M, et al.: Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-IV), Clinician Version (Administrative Booklet). Washington, DC: American Psychiatric Association, 1997.

Ventura J, Liberman RP, Green MF, et al.: Training and quality assurance with the Structured Clinical Interview for DSM-IV (SCID-IV). Psychiatry Res. 1998; 79(2): 163-173.

Tarvainen MP, Niskanen JP: Kubios HRV Analysis, Version 2.0 beta, User’s Guide. , Kuopio, Finland: Biosignal Analysis and Medical Imaging Group (BSAMIG), Department of Physics, University of Kuopio, 2006.

Tucker P, Pfefferbaum B, North CS, et al.: Physiologic reactivity despite emotional resilience several years after direct exposure to terrorism. Am J Psychiatry. 2007; 164(2): 230-235.

Pitman RK, Orr SP, Forgue DF, et al.: Psychophysiological assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Arch Gen Psychiatry. 1987; 44: 970-975.

Shalev AY, Orr SP, Pitman RK: Psychophysiologic assessment of traumatic imagery in Israeli civilian patients with posttraumatic stress disorder. Am J Psychiatry. 1993; 150: 620-624.

Tucker P, Pfefferbaum B, Khan Q, et al.: Katrina survivors relocated to Oklahoma: A tale of two cities. Psychiatr Ann. 2008; 38(2): 125-133.

Guinjoan SM; Vigo DE; Castro MN, et al.: Mood, Th-1/Th-2 cytokine profile, and autonomic activity in older adults with acute/decompensated heart failure: Preliminary observations. World J Biol Psychiatry. 2009; 10(4 Pt 3): 913-918.




DOI: http://dx.doi.org/10.5055/ajdm.2018.0306

Refbacks

  • There are currently no refbacks.
This site uses cookies to maintain session information critical to the user's experience and environment on this system. Click "Accept Cookies" to continue.
For more details please visit our privacy statement at: Privacy & GDPR