Cognitive function, health-related quality of life, and symptoms of depression and anxiety sensitivity are impaired in patients with the postural orthostatic tachycardia syndrome (POTS)

Jake W Anderson, Elisabeth A Lambert, Carolina I Sari, Tye Dawood, Murray D Esler, Gautam Vaddadi, Gavin W Lambert, Jake W Anderson, Elisabeth A Lambert, Carolina I Sari, Tye Dawood, Murray D Esler, Gautam Vaddadi, Gavin W Lambert

Abstract

The Postural Orthostatic Tachycardia Syndrome (POTS) is a condition in which heart rate increases abnormally when the individual assumes an upright position. In addition to the marked tachycardia, presyncope, and syncope, patients with POTS often complain of light-headedness, fatigue, and difficulty in concentrating. The present study assessed individuals with POTS for psychiatric comorbidity, anxiety sensitivity and health related quality of life and examined general cognitive ability. Data was obtained from patients with POTS (n = 15, 12 female, aged 30 ± 3 years) and age matched healthy subjects (n = 30, 21 female, aged 32 ± 2 years). Patients with POTS commonly presented with symptoms of depression, elevated anxiety and increased anxiety sensitivity, particularly with regards to cardiac symptoms, and had a poorer health related quality of life in both the physical and mental health domains. While patients with POTS performed worse in tests of current intellectual functioning (verbal and non-verbal IQ) and in measures of focused attention (digits forward) and short term memory (digits back), test results were influenced largely by years of education and the underlying level of depression and anxiety. Acute changes in cognitive performance in response to head up tilt were evident in the POTS patients. From results obtained, it was concluded that participants with POTS have an increased prevalence of depression and higher levels of anxiety. These underlying symptoms impact on cognition in patients with POTS, particularly in the cognitive domains of attention and short-term memory. Our results indicate that psychological interventions may aid in recovery and facilitate uptake and adherence of other treatment modalities in patients with POTS.

Keywords: noradrenaline transporter; orthostatic intolerance; psychiatric comorbidity; sympathetic nervous system; tachycardia.

Figures

Figure 1
Figure 1
Health related quality of life. Polar plot indicating SF-36 domain scores in patients with POTS (▲) and in healthy subjects (•). Patients with POTS scored significantly worse in all domains, P < 0.001, n = 30 control and 15 POTS.
Figure 2
Figure 2
Heart rate response during head up tilt. Graph showing heart rate in the semi recumbent position and at 60° head up tilt in patients with POTS (▲) and in healthy subjects (•). *P < 0.05, n = 26 control and 11 POTS.
Figure 3
Figure 3
Cognitive testing during head up tilt. Bar graphs showing CogStat test results in the semi recumbent position and at 60° head up tilt in patients with POTS and in healthy subjects. *P < 0.05, n = 26 control and 11 POTS. Black bars indicate patients with POTS and white bars indicate healthy subjects.

References

    1. Austin M. P., Mitchell P., Goodwin G. M. (2001). Cognitive deficits in depression: possible implications for functional neuropathology. Br. J. Psychiatry 178, 200–206 10.1192/bjp.178.3.200
    1. Barton D. A., Dawood T., Lambert E. A., Esler M. D., Haikerwal D., Brenchley C., et al. (2007). Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J. Hypertens. 25, 2117–2124 10.1097/HJH.0b013e32829baae7
    1. Barton D. A., Esler M. D., Dawood T., Lambert E. A., Haikerwal D., Brenchley C., et al. (2008). Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch. Gen. Psychiatry 65, 38–46 10.1001/archgenpsychiatry.2007.11
    1. Bayles R., Harikrishnan K. N., Lambert E., Baker E. K., Agrotis A., Guo L., et al. (2012). Epigenetic modification of the norepinephrine transporter gene in postural tachycardia syndrome. Arterioscler. Thromb. Vasc. Biol. 32, 1910–1916 10.1161/ATVBAHA.111.244343
    1. Benrud-Larson L. M., Dewar M. S., Sandroni P., Rummans T. A., Haythornthwaite J. A., Low P. A. (2002). Quality of life in patients with postural tachycardia syndrome. Mayo Clin. Proc. 77, 531–537 10.4065/77.6.531
    1. Benrud-Larson L. M., Sandroni P., Haythornthwaite J. A., Rummans T. A., Low P. A. (2003). Correlates of functional disability in patients with postural tachycardia syndrome: preliminary cross-sectional findings. Health Psychol. 22, 643–648 10.1037/0278-6133.22.6.643
    1. Chalermpalanupap T., Kinkead B., Hu W. T., Kummer M. P., Hammerschmidt T., Heneka M. T., et al. (2013). Targeting norepinephrine in mild cognitive impairment and Alzheimer's disease. Alzheimers Res. Ther. 5:21 10.1186/alzrt175
    1. Clarke D. M., Currie K. C. (2009). Depression, anxiety and their relationship with chronic diseases: a review of the epidemiology, risk and treatment evidence. Med. J. Aust. 190, S54–S60
    1. Day J. J., Sweatt J. D. (2011). Epigenetic mechanisms in cognition. Neuron 70, 813–829 10.1016/j.neuron.2011.05.019
    1. Fu Q., Vangundy T. B., Shibata S., Auchus R. J., Williams G. H., Levine B. D. (2010). Menstrual cycle affects renal-adrenal and hemodynamic responses during prolonged standing in the postural orthostatic tachycardia syndrome. Hypertension 56, 82–90 10.1161/HYPERTENSIONAHA.110.151787
    1. Fu Q., Vangundy T. B., Shibata S., Auchus R. J., Williams G. H., Levine B. D. (2011). Exercise training versus propranolol in the treatment of the postural orthostatic tachycardia syndrome. Hypertension 58, 167–175 10.1161/HYPERTENSIONAHA.111.172262
    1. Ganzeboom K. S., Mairuhu G., Reitsma J. B., Linzer M., Wieling W., Van Dijk N. (2006). Lifetime cumulative incidence of syncope in the general population: a study of 549 Dutch subjects aged 35-60 years. J. Cardiovasc. Electrophysiol. 17, 1172–1176 10.1111/j.1540-8167.2006.00595.x
    1. Hamilton M. (1960). A rating scale for depression. J. Neurol. Neurosurg. Psychiatr. 23, 56–62 10.1136/jnnp.23.1.56
    1. Jacob G., Costa F., Shannon J. R., Robertson R. M., Wathen M., Stein M., et al. (2000). The neuropathic postural tachycardia syndrome. N. Engl. J. Med. 343, 1008–1014 10.1056/NEJM200010053431404
    1. Jacobs E., D'esposito M. (2011). Estrogen shapes dopamine-dependent cognitive processes: implications for women's health. J. Neurosci. 31, 5286–5293 10.1523/JNEUROSCI.6394-10.2011
    1. Komesaroff P. A., Esler M. D., Sudhir K. (1999). Estrogen supplementation attenuates glucocorticoid and catecholamine responses to mental stress in perimenopausal women. J. Clin. Endocrinol. Metab. 84, 606–610 10.1210/jcem.84.2.5447
    1. Komesaroff P. A., Fullerton M., Esler M. D., Jennings G., Sudhir K. (2002). Oestrogen supplementation attenuates responses to psychological stress in elderly men rendered hypogonadal after treatment for prostate cancer. Clin. Endocrinol. (Oxf.) 56, 745–753 10.1046/j.1365-2265.2002.01542.x
    1. Lambert E., Eikelis N., Esler M., Dawood T., Schlaich M., Bayles R., et al. (2008). Altered sympathetic nervous reactivity and norepinephrine transporter expression in patients with postural tachycardia syndrome. Circ. Arrhythm. Electrophysiol. 1, 103–109 10.1161/CIRCEP.107.750471
    1. Lambert G., Johansson M., Agren H., Friberg P. (2000). Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch. Gen. Psychiatry 57, 787–793 10.1001/archpsyc.57.8.787
    1. Lambert G. W., Hering D., Esler M. D., Marusic P., Lambert E. A., Tanamas S. K., et al. (2012). Health-related quality of life after renal denervation in patients with treatment-resistant hypertension. Hypertension 60, 1479–1484 10.1161/HYPERTENSIONAHA.112.200865
    1. Linzer M., Pontinen M., Gold D. T., Divine G. W., Felder A., Brooks W. B. (1991). Impairment of physical and psychosocial function in recurrent syncope. J. Clin. Epidemiol. 44, 1037–1043 10.1016/0895-4356(91)90005-T
    1. Low P. A., Opfer-Gehrking T. L., Textor S. C., Benarroch E. E., Shen W. K., Schondorf R., et al. (1995). Postural tachycardia syndrome (POTS). Neurology 45, S19–S25
    1. Maruff P., Thomas E., Cysique L., Brew B., Collie A., Snyder P., et al. (2009). Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex. Arch. Clin. Neuropsychol. 24, 165–178 10.1093/arclin/acp010
    1. McGrady A., Kern-Buell C., Bush E., Khuder S., Grubb B. P. (2001). Psychological and physiological factors associated with tilt table testing for neurally mediated syncopal syndromes. Pacing Clin. Electrophysiol. 24, 296–301 10.1046/j.1460-9592.2001.00296.x
    1. Minson C. T., Halliwill J. R., Young T. M., Joyner M. J. (2000). Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women. Circulation 101, 862–868 10.1161/01.CIR.101.8.862
    1. Moldovanova I., Schroeder C., Jacob G., Hiemke C., Diedrich A., Luft F. C., et al. (2008). Hormonal influences on cardiovascular norepinephrine transporter responses in healthy women. Hypertension 51, 1203–1209 10.1161/HYPERTENSIONAHA.107.107433
    1. Ocon A. J., Medow M. S., Taneja I., Clarke D., Stewart J. M. (2009). Decreased upright cerebral blood flow and cerebral autoregulation in normocapnic postural tachycardia syndrome. Am. J. Physiol. Heart Circ. Physiol. 297, H664–673 10.1152/ajpheart.00138.2009
    1. Ocon A. J., Messer Z. R., Medow M. S., Stewart J. M. (2012). Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome. Clin. Sci. (Lond.) 122, 227–238 10.1042/CS20110241
    1. Raj S. R., Black B. K., Biaggioni I., Harris P. A., Robertson D. (2005). Acetylcholinesterase inhibition improves tachycardia in postural tachycardia syndrome. Circulation 111, 2734–2740 10.1161/CIRCULATIONAHA.104.497594
    1. Raj S. R., Black B. K., Biaggioni I., Paranjape S. Y., Ramirez M., Dupont W. D., et al. (2009a). Propranolol decreases tachycardia and improves symptoms in the postural tachycardia syndrome: less is more. Circulation 120, 725–734 10.1161/CIRCULATIONAHA.108.846501
    1. Raj V., Haman K. L., Raj S. R., Byrne D., Blakely R. D., Biaggioni I., et al. (2009b). Psychiatric profile and attention deficits in postural tachycardia syndrome. J. Neurol. Neurosurg. Psychiatr. 80, 339–344 10.1136/jnnp.2008.144360
    1. Rosano G. M., Leonardo F., Sarrel P. M., Beale C. M., De Luca F., Collins P. (1996). Cyclical variation in paroxysmal supraventricular tachycardia in women. Lancet 347, 786–788
    1. Rosenberg L., Park S. (2002). Verbal and spatial functions across the menstrual cycle in healthy young women. Psychoneuroendocrinology 27, 835–841
    1. Schmitt J. A., Wingen M., Ramaekers J. G., Evers E. A., Riedel W. J. (2006). Serotonin and human cognitive performance. Curr. Pharm. Des. 12, 2473–2486 10.2174/138161206777698909
    1. Schroeder C., Adams F., Boschmann M., Tank J., Haertter S., Diedrich A., et al. (2004). Phenotypical evidence for a gender difference in cardiac norepinephrine transporter function. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R851–856 10.1152/ajpregu.00689.2003
    1. Shannon J. R., Flattem N. L., Jordan J., Jacob G., Black B. K., Biaggioni I., et al. (2000). Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency. N. Engl. J. Med. 342, 541–549 10.1056/NEJM200002243420803
    1. Sheehan D. V., Lecrubier Y., Sheehan K. H., Amorim P., Janavs J., Weiller E., et al. (1998). The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J. Clin. Psychiatry 59(Suppl. 20), 22–33
    1. Shibata S., Fu Q., Bivens T. B., Hastings J. L., Wang W., Levine B. D. (2012). Short-term exercise training improves the cardiovascular response to exercise in the postural orthostatic tachycardia syndrome. J. Physiol. 590, 3495–3505 10.1113/jphysiol.2012.233858
    1. Stewart J. M., Medow M. S., Messer Z. R., Baugham I. L., Terilli C., Ocon A. J. (2012). Postural neurocognitive and neuronal activated cerebral blood flow deficits in young chronic fatigue syndrome patients with postural tachycardia syndrome. Am. J. Physiol. Heart Circ. Physiol. 302, H1185–H1194 10.1152/ajpheart.00994.2011
    1. Sun B. C., Emond J. A., Camargo C. A., Jr. (2005). Direct medical costs of syncope-related hospitalizations in the United States. Am. J. Cardiol. 95, 668–671 10.1016/j.amjcard.2004.11.013
    1. Taylor S., Cox B. J. (1998). Anxiety sensitivity: multiple dimensions and hierarchic structure. Behav. Res. Ther. 36, 37–51 10.1016/S0005-7967(97)00071-5
    1. Thakur G. A., Sengupta S. M., Grizenko N., Choudhry Z., Joober R. (2012). Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy. PLoS ONE 7:e49616 10.1371/journal.pone.0049616
    1. Ware J. E., Jr., Sherbourne C. D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med. Care 30, 473–483 10.1097/00005650-199206000-00002
    1. Weschler D. (1997). Wechsler Adult Intelligence Scale-III (WAIS-III). New York, NY: The Psychological Corporation
    1. Wechsler D. (1999). Manual for the Wechsler Abbreviated Intelligence Scale (WASI). San Antonio, TX: The Physiological Corporation
    1. Wingen M., Kuypers K. P., Van De Ven V., Formisano E., Ramaekers J. G. (2008). Sustained attention and serotonin: a pharmaco-fMRI study. Hum. Psychopharmacol. 23, 221–230 10.1002/hup.923

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