British Journal of Psychiatry (1992),161, 831—835

Cardiac

Vagal Tone in Generalised

Anxiety Disorder

MARK KOLLAI and BALAZS KOLLAI

Theaimof the presentstudy wastwofold: firstly, to determinecardiacvagaltone in subjects with generalisedanxiety disorderdirectly, using an invasivepharmacologicalmethod; and secondly,to test whetherthe non-invasivemethodof measuringthe amplitudeof respiratory sinus arrhythmia (RSA) gives a reliable estimate of cardiac vagal tone in this form of anxiety

disorder.Comparisonof baselinephysiologicalmeasuresof anxiousand control subjects revealedthat cardiac vagal tone and heart rate were not different in the two groups of subjects, whereas length of the respiratory cycle and amplitude of respiratory sinus arrhythmia were reducedintheformergroup.Becauseof thehigherrespiratory ratesof

anxioussubjects,the RSAmethodwasfoundto underestimatecardiacvagaltoneingeneralised anxiety disorder. Acute psychologicalstressinducessomatic changes, hyperactivity, although it is common knowledgethat cardiac chronotropism is under the dual control of including activation of the cardiovascular, respiratory, and musculoskeletalsystems(Lader, 1980).Tachy both the sympatheticand parasympatheticsystems, cardia is invariably present. Since anxiety is associated and that in man the parasympathetic systemexerts with symptoms that resemble those produced by the predominant influence on cardiac pacemaker acute stress, it has been assumedthat chronically function (Berne& Levy, 1988).Hencethe tachycardia of anxiety disorders could be the result of either anxious patients are in a state of persistent autonomic parasympathetic withdrawal or sympathetic acti arousal (Hoehn-Saric eta!, 1989a). This implies that anxiouspatientshavehigher heart ratesthan normal vation, or both. In anaesthetisedanimals activation controls. However, in mixed neurotic populations of the hypothalamic arousal area results in strong with heightened anxiety, baseline heart rate was inhibition of ongoing cardiac vagal discharges found to be elevated in some studies (Wishner, 1953; (Koizumi & Kollai, 1981).Little is known about the Kelly et a!, 1970;Kelly, 1980)and normal in others involvement of cardiac vagal activity in human (Jurko et a!, 1952;Ackner, 1956;Goldstein, 1964). pathological anxiety. Vagal inhibition - although not proven by direct means—¿ most likely contributes to Since DSM—III (American Psychiatric Association, 1980) has differentiated severalanxiety states, most the tachycardia that developsduring panic attacks of the anxietystudieshavebeenconcernedwith panic (Taylor et a!, 1986), and reduced parasympathetic disorders. Panic attacks were regularly found to be activity has also been suggestedbetween attacks associatedwith considerabletachycardia (Freedman becausethe resting tachycardia of panic patients et a!, 1985; Taylor et a!, 1986; Shear et a!, 1987) could not be explained on the basis of plasma but elevated heart rate and plasma catecholamine catecholamine levels (Nesseeta!, 1984). The potential levels were observedbetweenpanic attacks as well importance of the question stems from the evidence that normal parasympathetic tone and responsiveness appears to promote good health and may serve to protect the heart, while reduced cardiac vagal control

(Freedman et a!, 1984; Nesse et al, 1984; Liebowitz

eta!, 1985;Gorman eta!, 1988).In contrast to panic disorder, few data areavailableon cardiacautonomic mechanismsin generalisedanxiety disorder (GAD), a chronic anxiety condition defined as a state of increasedapprehensionthat is frequentlyaccompanied by hyperarousal. During the acute phases,patients with GAD report ‘¿racing and pounding heart', palpitations and sweating. However, not much is known about cardiac autonomic function in the restingcondition;some studiesindicatednormal

adrenergic activity (Mathew et a!, 1982; Peronnet et a!, 1986; Hoehn-Saric et a!, 1989a). Curiously, in the psychiatric and psychophysiologi

has been associated with cardiovascular disease (Eckberg, 1983). Therefore, if chronic anxiety is associated with reduced cardiac vagal tone, then anxietypatients,who constitutea largeproportion of the ambulatory patient population (Charney et a!, 1984), are at an enhanced risk of developing

cardiovascular dysfunction. The most frequently used non-invasive way to measurecardiac vagal tone is to record respiratory sinus arrhythmia (RSA). In brief, the method that

cal literature, the tachycardia of mental disordersis

takes RSA as an index of vagal tone is based on the linear relationship that was established in anaesthe

almost always appreciated as a sign of beta-adrenergic

tised animals between the amplitude of RSA and

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KOLLAI & KOLLAI

cardiac vagal tone, the latter determined invasively by pharmacologicalmeans(Katona & Jih, 1975). The method has been transferred to and is widely used in

clinical and psychophysiologicalstudies.It hasbeen demonstrated recently, however, that the RSA-vagal

tone relationshipis influencedby respiratoryrate and pattern in conscious human subjects (Kollai & Mizsei, 1990). Since rapid shallow breathing and occasionalhyperventilation are frequently observed in the various forms of anxiety (Gorman & Uy,

1987), the method's validity needsto be tested in such conditions. In view of this, and becauseof the paucity of physiological studies, the present work was under taken (a) to determine cardiac vagal tone in patients with GAD directly by pharmacological means; and

(b) to establishto what extent the amplitude of RSA can be taken asan indirect measureof cardiac vagal tone in this anxiety state.

correspondingto late inspiration or early expiration was substractedfrom the longestexpiration-relatedinterval.The breath-by-breath differences werethenaveraged across respiratory cycles for the measurement period, which lasted

for at least 5 minutes to include severalnon-respiratory slow-wavefluctuations intheR—Rinterval, iftherewere

any.Atrophicsulphatewasinjectedintravenouslyin doses of 5 pg/kg at 3-minuteintervals,until two consecutivedoses produced no further increase in heart rate or a total dose

of40pg/kgwasreached. Cardiac vagaltonewasdefined as the dose of atropine required to produce complete functional vagotomy. Followingthe initial interviewandthe clinicalevaluations,

subjectsreportedto thelaboratoryfor twoadditionalvisits. During the first visit they filled out the questionnairesand weremadefamiliar with the recordingprocedure.Control subjects had participated previously in similar studies.

During the secondsessionphysiologicalmeasureswere recordedin the morning, at leasttwo hoursafter breakfast. Subjectswere lying supine in a quiet, isolated room with

an indwellingcatheterin the antecubitalvein. After a 15-minute baseline period, atropine was administered. Mean arterial blood pressure, mean HP, mean length of respiratory cycle, and the mean amplitude of RSA were determined during the last 5 minutes of rest period and after

Method Nineteen women with GAD (mean (s.d.) age 33.2 (6.7) years)were compared with 18 normal women (mean age 29.7 (4.6) years).All the patientshad requestedtreatment at the Thyroid Unit of the Balassa Janos Hospital, Budapest. The patients were originally referred with the

administration of atropine.

tentativediagnosisof hyperthyroidism;however,their

unpairedf-test. Relationshipsbetweenparameterswere

plasmalevelsof T3, T4 and thyroid-stimulating hormone (TSH), determined by radioimmunoassay, were within

analysedwith least-squareslinear regression.Differences were consideredsignificant when P

Cardiac vagal tone in generalised anxiety disorder.

The aim of the present study was twofold: firstly, to determine cardiac vagal tone in subjects with generalised anxiety disorder directly, using an in...
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