Research Article| Volume 226, 102660, July 2020

Download started.


Involuntary emotional expression disorder in postural tachycardia syndrome

  • Ramesh K. Khurana
    Department of Medicine, MedStar Union Memorial Hospital, 201 East University Parkway, Baltimore, MD 21218, United States of America.
    Department of Medicine, MedStar Union Memorial Hospital, Baltimore, MD, United States of America
    Search for articles by this author


      • PoTS patients displayed overt involuntary emotional expression disorder (IEED).
      • No obvious “structural” pathology was present in PoTS patients with IEED.
      • HUT was a precipitating factor for overt IEED in PoTS.
      • Latent IEED occurred frequently in both PoTS and NMH patients.
      • Higher PHQ-9 scores in PoTS and NMH patients indicated comorbid depression.



      To study the frequency of latent and overt involuntary emotional expression disorder (IEED) in postural tachycardia syndrome (PoTS).


      We compared 51 PoTS patients with 15 neurally mediated hypotension (NMH) patients and 12 control subjects using the Center for Neurologic Study-Lability Scale (CNS-LS) for latent IEED and the PHQ-9 questionnaire for depression screening before head-up tilt (HUT). Overt IEED occurrence was observed during HUT.


      HUT precipitated overt IEED in 11 (22%) PoTS patients but not in NMH patients or controls. CNS-LS identified latent IEED in 23 (45%) PoTS patients, 5 (33%) NMH patients, and no control subjects. The CNS-LS tearfulness subscale was elevated in PoTS patients compared with controls (P = 0.0006). The PHQ-9 questionnaire scores were elevated in 69% of PoTS patients and 47% of NMH patients. The PHQ-9 score was higher in PoTS (<0.0001) and NMH (P = 0.0002) patients compared with controls.


      The study demonstrated frequent occurrence of latent IEED in PoTS and NMH and overt IEED in PoTS without “structural” involvement. HUT was a specific trigger for overt IEED in PoTS. Depression was co-morbid with PoTS. Neurohumoral and cerebral blood flow changes in supine position along with reduced gray matter volume in the insula and cingulate gyrus may underlie susceptibility to IEED. During HUT, cerebral hypoperfusion, rising epinephrine levels, and augmented autonomic arousal provide underpinnings for overt IEED. Clinicians should recognize this entity and counsel PoTS patients and their families. Limiting the duration of orthostatic stress may reduce morbidity.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Autonomic Neuroscience: Basic and Clinical
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Anderson J.W.
        • Lambert E.A.
        • Sari C.I.
        • et al.
        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).
        Front. Physiol. 2014; 5 (doi): 230
        • Balaban C.D.
        Neural substrates linking balance control and anxiety.
        Physiol. Behav. 2002; 77: 469-475
        • Bandler R.
        • Keay K.A.
        Columnar organization in the midbrain periaqueductal gray and the integration of emotional expression.
        in: Holstege G. Bandler R. Saper C.B. Progress in Brain Research. 107. Publisher, City1996: 285-300
        • Basch E.
        • Torda P.
        • Adams K.
        Standards for patient-reported outcome-based performance measures.
        JAMA. 2013; 310 (doi:1710466 [pii];10.1001/jama.2013.6855 [doi]): 139-140
        • Benrud-Larson L.M.
        • Sandroni P.
        • Haythornthwaite J.A.
        • Rummans T.A.
        • Low P.A.
        Correlates of functional disability in patients with postural tachycardia syndrome: preliminary cross-sectional findings.
        Health Psychol. 2003; 22 ([doi];2003-09670-015 [pii]): 643-648
        • Cantril H.
        • Hunt W.A.
        Emotional effects produced by the injection of adrenalin.
        Circulation. 1932; 44: 300-307
        • Cummings J.L.
        • Arciniegas D.B.
        • Brooks B.R.
        • et al.
        Defining and diagnosing involuntary emotional expression disorder.
        CNS Spectr. 2006; 11: 1-7
        • Del Pozzi A.T.
        • Pandey A.
        • Medow M.S.
        • Messer Z.R.
        • Stewart J.M.
        Blunted cerebral blood flow velocity in response to a nitric oxide donor in postural tachycardia syndrome.
        Am. J. Physiol. Heart Circ. Physiol. 2014; 307: H397-H404
        • Freeman R.
        • Wieling W.
        • Axelrod F.B.
        • et al.
        Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.
        Clin. Auton. Res. 2011; 21: 69-72
        • Frohlich E.D.
        • Dustan H.P.
        • Page I.H.
        Hyperdynamic beta-adrenergic circulatory state.
        Arch. Intern. Med. 1966; 117: 614-619
        • Garland E.M.
        • Raj S.R.
        • Black B.K.
        • Harris P.A.
        • Robertson D.
        The hemodynamic and neurohumoral phenotype of postural tachycardia syndrome.
        Neurology. 2007; 69: 790-798
        • Goldstein D.S.
        • Eldadah B.
        • Holmes C.
        • Pechnik S.
        • Moak J.
        • Sharabi Y.
        Neurocirculatory abnormalities in chronic orthostatic intolerance.
        Circulation. 2005; 111: 839-845
        • Gray M.A.
        • Beacher F.D.
        • Minati L.
        • et al.
        Emotional appraisal is influenced by cardiac afferent information.
        Emotion. 2012; 12: 180-191
        • Grubb B.P.
        • Gerard G.
        • Roush K.
        • et al.
        Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response.
        Circulation. 1991; 84: 1157-1164
        • Poeck K.
        Pathophysiology of emotional disorders associated with brain damage.
        Handbook Clin Neurol. 1969; 3: 343-367
        • Hermosillo A.G.
        • Jauregui-Renaud K.
        • Kostine A.
        • Marquez M.F.
        • Lara J.L.
        • Cardenas M.
        Comparative study of cerebral blood flow between postural tachycardia and neurocardiogenic syncope, during head-up tilt test.
        Europace. 2002; 4: 369-374
        • Horton E.
        • Krishnamoorthy S.
        • Reynolds L.
        Bickerstaff’s encephalitis.
        BMJ Case Rep. 2014; 2014
        • Joo E.Y.
        • Hong S.B.
        • Lee M.
        • et al.
        Cerebral blood flow abnormalities in patients with neurally mediated syncope.
        J. Neurol. 2011; 258: 366-372
        • Kesarwani R.
        • Sankar T.
        • Ba F.
        Acute and reversible crying following deep brain stimulation targeting the globus pallidus interna in dystonia.
        J. Neurol. Sci. 2018; 388: 76-78
        • Khurana R.K.
        Orthostatic intolerance and orthostatic tachycardia: a heterogeneous disorder.
        Clin. Auton. Res. 1995; 5: 12-18
        • Khurana R.K.
        in: Schuster M.M. Crowell M.D. Koch K.L. Schuster Atlas of Gastrointestinal Motility. BC Decker, Inc, Hamilton, Ontario2002: 335-351
        • Khurana R.K.
        Experimental induction of panic-like symptoms in patients with postural tachycardia syndrome.
        Clin. Auton. Res. 2006; 16: 371-377
        • Khurana R.K.
        Visceral sensitization in postural tachycardia syndrome.
        Clin. Auton. Res. 2014; 24: 71-76
        • Khurana R.K.
        Pseudobulbar affect in postural tachycardia syndrome.
        Clin. Auton. Res. 2017; 27: 295-353
        • Kuhlmann L.
        • Foster B.L.
        • Liley D.T.
        Modulation of functional EEG networks by the NMDA antagonist nitrous oxide.
        PLoS One. 2013; 8e56434
        • Makovac E.
        • Garfinkel S.
        • Bassi A.
        • et al.
        Fear processing is differentially affected by lateralized stimulation of carotid baroreceptors.
        Cortex. 2018; 99: 200-212
        • Martin A.N.
        • Dillon P.M.
        • Jones D.E.
        • Brenin D.R.
        • Lapides D.A.
        Anti-yo mediated paraneoplastic cerebellar degeneration associated with pseudobulbar affect in a patient with breast cancer.
        Case Rep Oncol Med. 2017; 2017: 8120689
        • Minden S.L.
        • Feinstein A.
        • Kalb R.C.
        • et al.
        Evidence-based guideline: assessment and management of psychiatric disorders in individuals with MS: report of the Guideline Development Subcommittee of the American Academy of Neurology.
        Neurology. 2014; 82: 174-181
        • Moore S.R.
        • Gresham L.S.
        • Bromberg M.B.
        • Kasarkis E.J.
        • Smith R.A.
        A self report measure of affective lability.
        J. Neurol. Neurosurg. Psychiatry. 1997; 63: 89-93
        • Novak V.
        • Novak P.
        • Opfer-Gehrking T.L.
        • O’Brien P.C.
        • Low P.A.
        Clinical and laboratory indices that enhance the diagnosis of postural tachycardia syndrome.
        Mayo Clin. Proc. 1998; 73 (doi: S0025-6196(11)64483-2 [pii];10.4065/73.12.1141 [doi]): 1141-1150
        • Parvizi J.
        • Anderson S.W.
        • Martin C.O.
        • Damasio H.
        • Damasio A.R.
        Pathological laughter and crying: a link to the cerebellum.
        Brain. 2001; 124: 1708-1719
        • Pederson C.L.
        • Brook J.B.
        Health-related quality of life and suicide risk in postural tachycardia syndrome.
        Clin. Auton. Res. 2017; 27: 75-81
        • Raj V.
        • Opie M.
        • Arnold A.C.
        Cognitive and psychological issues in postural tachycardia syndrome.
        Auton. Neurosci. 2018; 215: 46-55
        • Rathore J.S.
        • Jehi L.E.
        • Fan Y.
        • et al.
        Validation of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in adults with epilepsy.
        Epilepsy Behav. 2014; 37 (doi: S1525-5050(14)00247-9 [pii];10.1016/j.yebeh.2014.06.030 [doi]): 215-220
        • Rau H.
        • Pauli P.
        • Brody S.
        • Elbert T.
        • Birbaumer N.
        Baroreceptor stimulation alters cortical activity.
        Psychophysiology. 1993; 30: 322-325
        • Sackeim H.A.
        • Greenberg M.S.
        • Weiman A.L.
        • Gur R.C.
        • Hungerbuhler J.P.
        • Geschwind N.
        Hemispheric asymmetry in the expression of positive and negative emotions. Neurologic evidence.
        Arch. Neurol. 1982; 39: 210-218
        • Shoemaker J.K.
        • Goswami R.
        Forebrain neurocircuitry associated with human reflex cardiovascular control.
        Front. Physiol. 2015; 6: 240
        • Smith R.
        • Allen J.J.
        • Thayer J.F.
        • Lane R.D.
        Altered functional connectivity between medial prefrontal cortex and the inferior brainstem in major depression during appraisal of subjective emotional responses: a preliminary study.
        Biol. Psychol. 2015; 108: 13-24
        • Stewart J.M.
        • Del Pozzi A.T.
        • Pandey A.
        • Messer Z.R.
        • Terilli C.
        • Medow M.S.
        Oscillatory cerebral blood flow is associated with impaired neurocognition and functional hyperemia in postural tachycardia syndrome during graded tilt.
        Hypertension. 2015; 65: 636-643
        • Subramanian H.H.
        • Arun M.
        • Silburn P.A.
        • Holstege G.
        Motor organization of positive and negative emotional vocalization in the cat midbrain periaqueductal gray.
        J. Comp. Neurol. 2016; 524: 1540-1557
        • Taggart P.
        • Critchley H.
        • van Duijvendoden S.
        • Lambiase P.D.
        Significance of neuro-cardiac control mechanisms governed by higher regions of the brain.
        Auton. Neurosci. 2016; 199: 54-65
        • Umeda S.
        • Harrison N.A.
        • Gray M.A.
        • Mathias C.J.
        • Critchley H.D.
        Structural brain abnormalities in postural tachycardia syndrome: a VBM-DARTEL study.
        Front. Neurosci. 2015; 9: 34
        • Wali G.M.
        “Fou rire prodromique” heralding a brainstem stroke.
        J. Neurol. Neurosurg. Psychiatry. 1993; 56: 209-210
        • Warnock J.K.
        • Bundren J.C.
        Anxiety and mood disorders associated with gonadotropin-releasing hormone agonist therapy.
        Psychopharmacol. Bull. 1997; 33: 311-316
        • Wilson S.A.K.
        Some problems in neurology: no. 2. Pathological laughing and crying.
        J. Neurol. Psychopathol. 1924; 4: 299-333
        • Work S.S.
        • Colamonico J.A.
        • Bradley W.G.
        • Kaye R.E.
        Pseudobulbar affect: an under-recognized and under-treated neurological disorder.
        Adv. Ther. 2011; 28: 586-601