Research & Scholarship

Current Research and Scholarly Interests

Laboratory and ambulatory recording of physiological, responses to stressors in anxious and phobic patients.


2010-11 Courses


Journal Articles

  • An affective computing approach to physiological emotion specificity: Toward subject-independent and stimulus-independent classification of film-induced emotions PSYCHOPHYSIOLOGY Kolodyazhniy, V., Kreibig, S. D., Gross, J. J., Roth, W. T., Wilhelm, F. H. 2011; 48 (7): 908-922


    The hypothesis of physiological emotion specificity has been tested using pattern classification analysis (PCA). To address limitations of prior research using PCA, we studied effects of feature selection (sequential forward selection, sequential backward selection), classifier type (linear and quadratic discriminant analysis, neural networks, k-nearest neighbors method), and cross-validation method (subject- and stimulus-(in)dependence). Analyses were run on a data set of 34 participants watching two sets of three 10-min film clips (fearful, sad, neutral) while autonomic, respiratory, and facial muscle activity were assessed. Results demonstrate that the three states can be classified with high accuracy by most classifiers, with the sparsest model having only five features, even for the most difficult task of identifying the emotion of an unknown subject in an unknown situation (77.5%). Implications for choosing PCA parameters are discussed.

    View details for DOI 10.1111/j.1469-8986.2010.01170.x

    View details for Web of Science ID 000291255500004

    View details for PubMedID 21261632

  • Effects of Breathing Training on Voluntary Hypo- and Hyperventilation in Patients with Panic Disorder and Episodic Anxiety APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Wollburg, E., Roth, W. T., Kim, S. 2011; 36 (2): 81-91


    Anxiety disorders are associated with respiratory abnormalities. Breathing training (BT) aimed at reversing these abnormalities may also alter the anxiogenic effects of biological challenges. Forty-five Panic Disorder (PD) patients, 39 Episodic Anxiety patients, and 20 non-anxious controls underwent voluntary hypoventilation and hyperventilation tests twice while psychophysiological measures were recorded. Patients were randomized to one of two BT therapies (Lowering vs. Raising pCO(2)) or to a waitlist. Before treatment panic patients had higher respiration rates and more tidal volume instability and sighing at rest than did non-anxious controls. After the Lowering therapy, patients had lower pCO(2) during testing. However, neither reactivity nor recovery to either test differed between patients and controls, or were affected by treatment. Although the two treatments had their intended opposite effects on baseline pCO(2), other physiological measures were not affected. We conclude that baseline respiratory abnormalities are somewhat specific to PD, but that previously reported greater reactivity and slower recovery to respiratory challenges may be absent.

    View details for DOI 10.1007/s10484-011-9150-5

    View details for Web of Science ID 000290026100003

    View details for PubMedID 21373936

  • Methodological considerations in ambulatory skin conductance monitoring INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Doberenz, S., Roth, W. T., Wollburg, E., Maslowski, N. I., Kim, S. 2011; 80 (2): 87-95


    Little is known how much skin conductance (SC) recordings from the fingers are affected by factors such as electrode site deterioration, ambient temperature (TMP), or physical activity (ACT), or by age, sex, race, or body mass index. We recorded SC, TMP, and ACT in 48 healthy control subjects for a 24-hour period, and calculated SC level (SCL), its standard deviation, the coefficient of SC variation, and frequency and amplitude of non-specific SC fluctuations. One method of assessing electrode site deterioration showed an average decline of 20%, while a second method found no significant change. All SC measures were higher during waking than sleep. Other factors influenced different measures in different ways. Thus, 24-hour SC recording outside the laboratory is feasible, but some measures need to be corrected for the influence of confounding variables.

    View details for DOI 10.1016/j.ijpsycho.2011.02.002

    View details for Web of Science ID 000290648300001

    View details for PubMedID 21320551

  • Affective modulation of the acoustic startle: Does sadness engage the defensive system? BIOLOGICAL PSYCHOLOGY Kreibig, S. D., Wilhelm, F. H., Roth, W. T., Gross, J. J. 2011; 87 (1): 161-163


    It has been suggested that high arousal negative affective states, but not low arousal negative affective states, potentiate the startle response. Because sadness has generally been studied as a low arousal emotion, it remains unclear whether high arousal sadness would produce startle potentiation to a similar degree as high arousal fear. To address this issue, 32 participants viewed two sets of 10-min film clips selected to induce two affective states of high subjective arousal (fear, sadness) and a neutral state of low subjective arousal, while the eyeblink startle response associated with brief noise bursts was assessed using orbicularis oculi EMG. Larger blink magnitude was found for fearful than for sad or neutral clips. Implications for conceptualizing sadness are discussed.

    View details for DOI 10.1016/j.biopsycho.2011.02.008

    View details for Web of Science ID 000290195100020

    View details for PubMedID 21352887

  • Twenty-four hour skin conductance in panic disorder JOURNAL OF PSYCHIATRIC RESEARCH Doberenz, S., Roth, W. T., Wollburg, E., Breuninger, C., Kim, S. 2010; 44 (16): 1137-1147


    Skin conductance, physical activity, ambient temperature and mood were recorded for 24 h in 22 panic disorder (PD) patients and 29 healthy controls. During the day, subjects performed standardized relaxation tests (ARTs). We hypothesized that tonically elevated anticipatory anxiety in PD during waking and sleeping would appear as elevated skin conductance level (SCL) and greater skin conductance (SC) variability. Mean SCL was higher during both usual waking activities and sleeping in PD, but not during the ARTs. Group SC variability differences did not reach significance, perhaps because of variance unrelated to anxiety. Analyses indicated that in the PD group, antidepressant medication reduced mean SCL whereas state anxiety had the opposite effect during the day. Depressive symptoms reported during the day were related to elevated mean SCL on the night of the recording. The rate and extent of SCL deactivation over the night was equal in the two groups. However, PD patients had more frequent interruptions of deactivation that could have arisen from conditioned arousal in response to threat cues during sleep.

    View details for DOI 10.1016/j.jpsychires.2010.04.012

    View details for Web of Science ID 000285952000003

    View details for PubMedID 20537349



    By comparing efficacious psychological therapies of different kinds, inferences about common effective treatment mechanisms can be made. We selected six therapies for review on the basis of the diversity of their theoretical rationales and evidence for superior efficacy: psychoanalytic psychotherapy, hypercapnic breathing training, hypocapnic breathing training, reprocessing with and without eye-movement desensitization, muscle relaxation, and cognitive behavior therapy. The likely common element of all these therapies is that they reduce the immediate expectancy of a panic attack, disrupting the vicious circle of fearing fear. Modifying expectation is usually regarded as a placebo mechanism in psychotherapy, but may be a specific treatment mechanism for panic. The fact that this is seldom the rationale communicated to the patient creates a moral dilemma: Is it ethical for therapists to mislead patients to help them? Pragmatic justification of a successful practice is a way out of this dilemma. Therapies should be evaluated that deal with expectations directly by promoting positive thinking or by fostering non-expectancy.

    View details for DOI 10.1002/da.20601

    View details for Web of Science ID 000273468300002

    View details for PubMedID 20049938

  • Does improving mood in depressed patients alter factors that may affect cardiovascular disease risk? JOURNAL OF PSYCHIATRIC RESEARCH Taylor, C. B., Conrad, A., Wilhelm, F. H., Strachowski, D., Khaylis, A., Neri, E., Giese-Davis, J., Roth, W. T., Cooke, J. P., Kraemer, H., Spiegel, D. 2009; 43 (16): 1246-1252


    To determine if improvement in mood would ameliorate autonomic dysregulation, HPA dysfunction, typical risk factors and C-reactive protein in depressed patients with elevated cardiovascular disease risk (CVD), 48 depressed participants with elevated cardiovascular risk factors were randomized to a cognitive behavioral intervention (CBT) or a waiting list control (WLC) condition. Twenty non-depressed age and risk-matched controls were also recruited. Traditional risk factors (e.g., lipids, blood pressure) and C-reactive protein were assessed pre- and post-treatment six months later. Subjects also underwent a psychophysiological stress test while cardiovascular physiology was measured. Salivary cortisol was measured during the day and during the psychological stress test. At post-treatment, the CBT subjects were significantly less depressed than WLC subjects. There was no significant difference in change scores on any of the traditional risk factors or C-reactive protein, cortisol measures, or cardiovascular physiology, except for triglyceride levels and heart rate, which were significantly lower in treatment compared to control subjects. The normal controls exhibited no change in the variables measured during the same time. A significant improvement in mood may have little impact on most traditional or atypical risk factors, cortisol or cardiophysiology.

    View details for DOI 10.1016/j.jpsychires.2009.05.006

    View details for Web of Science ID 000272860300002

    View details for PubMedID 19577757

  • End-tidal versus transcutaneous measurement of PCO2 during voluntary hypo- and hyperventilation INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Wollburg, E., Roth, W. T., Kim, S. 2009; 71 (2): 103-108


    Recent studies have shown that end-tidal PCO(2) is lower during anxiety and stress, and that changing PCO(2) by altering breathing is therapeutic in panic disorder. However, end-tidal estimation of arterial PCO(2) has drawbacks that might be avoided by the transcutaneous measurement method. Here we compare transcutaneous and end-tidal PCO(2) under different breathing conditions in order to evaluate these methods in terms of their comparability and usability. Healthy volunteers performed two hypoventilation (slow vs. paused breathing) and two hyperventilation tests (25 mm Hg at 18 vs. 30 breaths per minute). Three measurements of PCO(2) (two end-tidal and one transcutaneous device), tidal volume, and respiration rate were recorded. Before and after each test, subjects filled out a symptom questionnaire. The results show that PCO(2) estimated by the two methods was comparable except that for transcutaneous measurement registration of changes in PCO(2) was delayed and absolute levels were much higher. Both methods documented that paused breathing was effective for raising PCO(2), a presumed antidote for anxious hyperventilation. We conclude that since the two methods give comparable results choosing between them for specific applications is principally a matter of whether the time lag of the transcutaneous method is acceptable.

    View details for DOI 10.1016/j.ijpsycho.2008.07.011

    View details for Web of Science ID 000263623800003

    View details for PubMedID 18706460

  • Circadian affective, cardiopulmonary, and cortisol variability in depressed and nondepressed individuals at risk for cardiovascular disease JOURNAL OF PSYCHIATRIC RESEARCH Conrad, A., Wilhelm, F. H., Roth, W. T., Spiegel, D., Taylor, C. B. 2008; 42 (9): 769-777


    Depression is a risk factor for cardiovascular disease (CVD) perhaps mediated by hypothalamic-pituitary-adrenal (HPA) axis or vagal dysregulation. We investigated circadian mood variation and HPA-axis and autonomic function in older (55 years) depressed and nondepressed volunteers at risk for CVD by assessing diurnal positive and negative affect (PA, NA), cortisol, and cardiopulmonary variables in 46 moderately depressed and 19 nondepressed volunteers with elevated CVD risk. Participants sat quietly for 5-min periods (10:00, 12:00, 14:00, 17:00, 19:00, and 21:00), and then completed an electronic diary assessing PA and NA. Traditional and respiration-controlled heart rate variability (HRV) variables were computed for these periods as an index of vagal activity. Salivary cortisols were collected at waking, waking+30min, 12:00, 17:00, and 21:00h. Cortisol peaked in the early morning after waking, and gradually declined over the day, but did not differ between groups. PA was lower and NA was higher in the depressed group throughout the day. HRV did not differ between groups. Negative emotions were inversely related to respiratory sinus arrhythmia in nondepressed participants. We conclude that moderately depressed patients do not show abnormal HPA-axis function. Diurnal PA and NA distinguish depressed from nondepressed individuals at risk for CVD, while measures of vagal regulation, even when controlled for physical activity and respiratory confounds, do not. Diurnal mood variations of older individuals at risk for CVD differ from those reported for other groups and daily fluctuations in NA are not related to cardiac autonomic control in depressed individuals.

    View details for DOI 10.1016/j.jpsychires.2007.08.003

    View details for Web of Science ID 000256651600009

    View details for PubMedID 17884093

  • Translational research for panic disorder AMERICAN JOURNAL OF PSYCHIATRY Roth, W. T. 2008; 165 (7): 796-798
  • Psychophysiological reactions to two levels of voluntary hyperventilation in panic disorder JOURNAL OF ANXIETY DISORDERS Wollburg, E., Meuret, A. E., Conrad, A., Roth, W. T., Kim, S. 2008; 22 (5): 886-898


    Panic disorder (PD) patients usually react with more self-reported distress to voluntary hyperventilation (HV) than do comparison groups. Less consistently PD patients manifest physiological differences such as more irregular breathing and slower normalization of lowered end-tidal pCO(2) after HV. To test whether physiological differences before, during, or after HV would be more evident after more intense HV, we designed a study in which 16 PD patients and 16 non-anxious controls hyperventilated for 3 min to 25 mmHg, and another 19 PD patients and another 17 controls to 20 mmHg. Patients reacted to HV to 20 mmHg but not to 25 mmHg with more self-reported symptoms than controls. However, at neither HV intensity were previous findings of irregular breathing and slow normalization of pCO(2) replicated. In general, differences between patients and controls in response to HV were in the cognitive-language rather than in the physiological realm.

    View details for DOI 10.1016/j.janxdis.2007.09.004

    View details for Web of Science ID 000256189100013

    View details for PubMedID 17950571

  • The psychophysiology of generalized anxiety disorder: 2. Effects of applied relaxation PSYCHOPHYSIOLOGY Conrad, A., Isaac, L., Roth, W. T. 2008; 45 (3): 377-388


    Muscle relaxation therapy assumes that generalized anxiety disorder (GAD) patients lack the ability to relax but can learn this in therapy. We tested this by randomizing 49 GAD patients to 12 weeks of Applied Relaxation (AR) or waiting. Before, during, and after treatment participants underwent relaxation tests. Before treatment, GAD patients were more worried than healthy controls (n=21) and had higher heart rates and lower end-tidal pCO2, but not higher muscle tension (A. Conrad, L. Isaac, & W.T. Roth, 2008). AR resulted in greater symptomatic improvement than waiting. However, 28% of the AR group dropped out of treatment and some patients relapsed at the 6-week follow-up. There was little evidence that AR participants learned to relax in therapy or that a reduction in anxiety was associated with a decrease in activation. We conclude that the clinical effects of AR in improving GAD symptoms are moderate at most and cannot be attributed to reducing muscle tension or autonomic activation.

    View details for DOI 10.1111/j.1469-8986.2007.00644.x

    View details for Web of Science ID 000254792100006

    View details for PubMedID 18221441

  • The psychophysiology of generalized anxiety disorder: 1. Pretreatment characteristics PSYCHOPHYSIOLOGY Conrad, A., Isaac, L., Roth, W. T. 2008; 45 (3): 366-376


    Generalized anxiety disorder (GAD) patients have been reported to have more muscle tension than controls, which has provided a rationale for treating them with muscle relaxation therapies (MRT). We tested this rationale by comparing 49 GAD patients with 21 controls. Participants underwent 5-min relaxation tests, during which they either just sat quietly (QS) or sat quietly and tried to relax (R). GAD patients reported themselves to be more worried during the assessment than the controls, had higher heart rates and lower end-tidal pCO2, but not higher muscle tension as measured by multiple EMGs. QS and R did not differ on most psychological and physiological measures, indicating that intention to relax did not affect speed of relaxation. In the GAD group, self-reported anxiety was not associated with electromyographic or autonomic measures. We conclude that GAD is not necessarily characterized by chronic muscle tension, and that this rationale for MRT should be reconsidered.

    View details for DOI 10.1111/j.1469-8986.2007.00601.x

    View details for Web of Science ID 000254792100005

    View details for PubMedID 18221449

  • Sympathetic activation in broadly defined generalized anxiety disorder JOURNAL OF PSYCHIATRIC RESEARCH Roth, W. T., Doberenz, S., Dietel, A., Conrad, A., Mueller, A., Wollburg, E., Meuret, A. E., Taylor, C. B., Kim, S. 2008; 42 (3): 205-212


    The definition of generalized anxiety disorder (GAD) has been narrowed in successive editions of DSM by emphasizing intrusive worry and deemphasizing somatic symptoms of hyperarousal. We tried to determine the clinical characteristics of more broadly defined chronically anxious patients, and whether they would show physiological signs of sympathetic activation. A group whose chief complaint was frequent, unpleasant tension over at least the last six weeks for which they desired treatment, was compared with a group who described themselves as calm. Participants were assessed with structured interviews and questionnaires. Finger skin conductance, motor activity, and ambient temperature were measured for 24h. Results show that during waking and in bed at night, runs of continuous minute-by-minute skin conductance level (SCL) declines were skewed towards being shorter in the tense group than in the calm group. In addition, during waking, distributions of minute SCLs were skewed towards higher levels in the tense group, although overall mean SCL did not differ. Thus, the tense group showed a failure to periodically reduce sympathetic tone, presumably a corollary of failure to relax. We conclude that broader GAD criteria include a substantial number of chronically anxious and hyperaroused patients who do not fall within standard criteria. Such patients deserve attention by clinicians and researchers.

    View details for DOI 10.1016/j.jpsychires.2006.12.003

    View details for Web of Science ID 000253397900005

    View details for PubMedID 17250853

  • Psychophysiological effects of breathing instructions for stress management APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK Conrad, A., Mueller, A., Doberenz, S., Kim, S., Meuret, A. E., Wollburg, E., Roth, W. T. 2007; 32 (2): 89-98


    Stressed and tense individuals often are recommended to change the way they breathe. However, psychophysiological effects of breathing instructions on respiration are rarely measured. We tested the immediate effects of short and simple breathing instructions in 13 people seeking treatment for panic disorder, 15 people complaining of daily tension, and 15 controls. Participants underwent a 3-hour laboratory session during which instructions to direct attention to breathing and anti-hyperventilation instructions to breathe more slowly, shallowly, or both were given. Respiratory, cardiac, and electrodermal measures were recorded. The anti-hyperventilation instructions failed to raise end-tidal pCO(2) above initial baseline levels for any of the groups because changes in respiratory rate were compensated for by changes in tidal volume and vice versa. Paying attention to breathing significantly reduced respiratory rate and decreased tidal volume instability compared to the other instructions. Shallow breathing made all groups more anxious than did other instructions. Heart rate and skin conductance were not differentially affected by instructions. We conclude that simple and short instructions to alter breathing do not change respiratory or autonomic measures in the direction of relaxation, except for attention to breathing, which increases respiratory stability. To understand the results of breathing instructions for stress and anxiety management, respiration needs to be monitored physiologically.

    View details for DOI 10.1007/s10484-007-9034-x

    View details for Web of Science ID 000247932100002

    View details for PubMedID 17520360

  • Physiological evaluation of psychological treatments for anxiety. Expert review of neurotherapeutics Wollburg, E., Kim, S., Conrad, A., Roth, W. T. 2007; 7 (2): 129-141


    Classification of mental disorders has been greatly influenced by a medical model postulating biological abnormalities that underlie its divisions. Particularly in anxiety disorders, physiological symptoms are part of the Diagnostic and Statistical Manual criteria. Therefore, successful therapy should influence physiological as well as cognitive-verbal expressions of anxiety. Nevertheless, despite the well-known limitations of self-report, physiological outcome measures have only occasionally been employed. We searched the literature for treatment studies that attempted to make a physiological argument for the efficacy of a psychological treatment for anxiety. Our search found only a few methodologically sound examples, where normalization of self-report and physiological measures corresponded. The most convincing studies dealt with the treatment of specific phobias and post-traumatic stress disorder.

    View details for PubMedID 17286547

  • Muscle relaxation therapy for anxiety disorders: It works but how? JOURNAL OF ANXIETY DISORDERS Conrad, A., Roth, W. T. 2007; 21 (3): 243-264


    Muscle relaxation therapy (MRT) has continued to play an important role in the modern treatment of anxiety disorders. Abbreviations of the original progressive MRT protocol [Jacobson, E. (1938). Progressive relaxation (2nd ed.). Chicago: University of Chicago Press] have been found to be effective in panic disorder (PD) and generalized anxiety disorder (GAD). This review describes the most common MRT techniques, summarizes recent evidence of their effectiveness in treating anxiety, and explains their rationale and physiological basis. We conclude that although GAD and PD patients may exhibit elevated muscle tension and abnormal autonomic and respiratory measures during laboratory baseline assessments, the available evidence does not allow us to conclude that physiological activation decreases over the course of MRT in GAD and PD patients, even when patients report becoming less anxious. Better-designed studies will be required to identify the mechanisms of MRT and to advance clinical practice.

    View details for DOI 10.1016/j.janxdis.2006.08.001

    View details for Web of Science ID 000245868500001

    View details for PubMedID 16949248

  • Psychophysiological and cortisol responses to psychological stress in depressed and nondepressed older men and women with elevated cardiovascular disease risk PSYCHOSOMATIC MEDICINE Taylor, C. B., Conrad, A., Wilhelm, F. H., Neri, E., DeLorenzo, A., Kramer, M. A., Giese-Davis, J., Roth, W. T., Oka, R., Cooke, J. P., Kraemer, H., Spiegel, D. 2006; 68 (4): 538-546


    The objective of this study was to compare psychophysiological and cortisol reactions to psychological stress in older depressed and nondepressed patients at risk for cardiovascular disease (CVD).Forty-eight depressed participants and 20 controls with elevated cardiovascular risk factors underwent a psychological stress test during which cardiovascular variables were measured. Salivary cortisol was collected after each test segment. Traditional (e.g., lipids) and atypical (e.g., C-reactive protein) CVD risk factors were also obtained.At baseline, the groups did not differ on lipid levels, flow-mediated vasodilation, body mass index, or asymmetric dimethylarginine. However, the depressed patients had significantly higher C-reactive protein levels. Contrary to our hypothesis, there were no differences in baseline cortisol levels or diurnal cortisol slopes, but depressed patients showed significantly lower cortisol levels during the stress test (p = .03) and less cortisol response to stress. Compared with nondepressed subjects, depressed subjects also showed lower levels of respiratory sinus arrhythmia (RSA(TF)) during the stress test (p = .02).In this sample, older depressed subjects with elevated risk for CVD exhibited a hypocortisol response to acute stress. This impaired cortisol response might contribute to chronic inflammation (as reflected in the elevated C-reactive proteins in depressed patients) and in other ways increase CVD risk. The reduced RSA(TF) activity may also increase CVD risk in depressed patients through impaired autonomic nervous system response to cardiophysiological demands.

    View details for DOI 10.1097/01.psy.0000222372.16274.92

    View details for Web of Science ID 000239330600005

    View details for PubMedID 16868262

  • Physiological markers for anxiety: Panic disorder and phobias INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY Roth, W. T. 2005; 58 (2-3): 190-198


    Physiological activation is a cardinal symptom of anxiety, although physiological measurement is still not used for psychiatric diagnosis. An ambulatory study of phobics who were afraid of highway driving showed a concordance between self-reported anxiety during driving, autonomic activation, hypocapnia, and sighing respiration. Patients with panic attacks do not exhibit autonomic activation when they are quietly sitting and not having panic attacks, but do have the same respiratory abnormalities as driving phobics, suggesting that these abnormalities could be a marker for panic disorder. Such abnormalities are compatible with both the false suffocation alarm (D. Klein) and hyperventilation (R. Ley) theories of panic. Hypocapnia, however, is often absent during full-blown panic attacks. Since activation functions as preparation for physical activity, it may not occur when a patient has learned that avoidance of fear by flight or fight is futile. We developed a capnometry feedback assisted breathing training therapy for panic disorder designed to reduce hyperventilation and making breathing regular. Without feedback, conventional therapeutic breathing instructions may actually increase hyperventilation by increasing dyspnea. Five weekly therapy sessions accompanied by daily home practice with a capnometer produced marked clinical improvement compared to changes in an untreated group. Improvement was sustained over a 12-month follow-up period. The therapist avoided any statements or procedures designed to alter cognitions. Improvement occurred regardless of whether patients initially reported mostly respiratory or non-respiratory symptoms during their attacks. There is evidence that modifying any of the three systems comprising a fear network can be therapeutic, as exemplified by cognitive therapy modifying thoughts, exposure therapy modifying avoidance, and breathing training procedures modifying pCO(2).

    View details for DOI 10.1016/j.ijpsycho.2005.01.015

    View details for Web of Science ID 000233383000010

    View details for PubMedID 16137780

  • Are current theories of panic falsifiable? PSYCHOLOGICAL BULLETIN Roth, W. T., Wilhelm, F. H., Pettit, D. 2005; 131 (2): 171-192


    The authors examine 6 theories of panic attacks as to whether empirical approaches are capable of falsifying them and their heuristic value. The authors conclude that the catastrophic cognitions theory is least falsifiable because of the elusive nature of thoughts but that it has greatly stimulated research and therapy. The vicious circle theory is falsifiable only if the frightening internal sensations are specified. The 3-alarms theory postulates an indeterminate classification of attacks. Hyperventilation theory has been falsified. The suffocation false alarm theory lacks biological parameters that unambiguously index dyspnea or its distinction between anticipatory and panic anxiety. Some correspondences postulated between clinical phenomena and brain areas by the neuroanatomical hypothesis may be falsifiable if panic does not depend on specific thoughts. All these theories have heuristic value, and their unfalsifiable aspects are capable of modification.

    View details for DOI 10.1037/0033-2909.1312.2.171

    View details for Web of Science ID 000227423200001

    View details for PubMedID 15740414

  • Psychophysiological assessment during exposure in driving phobic patients JOURNAL OF ABNORMAL PSYCHOLOGY Alpers, G. W., Wilhelm, F. H., Roth, W. T. 2005; 114 (1): 126-139


    A comprehensive assessment of fear or anxiety requires measurement of both self-report and physiological responses. Respiratory abnormalities have been rarely examined during real-life exposure, although they are an integral part of fear. Twenty-one women with a specific driving phobia and 17 nonphobic women were psychophysiologically monitored during 2 highway-driving sessions; phobic women completed an additional session. Respiratory movements, end-tidal partial pressure of carbon dioxide, an electrocardiogram, skin conductance, and skin temperature were recorded. Phobic patients differed from control participants both physiologically and experientially before, during, and after exposure. Effect size during exposure was large for the authors' measure of hyperventilation. Discriminant analysis indicated that multiple physiological measures contributed nonredundant information and correctly classified 95% of phobic and control participants. Thus, selected respiratory and autonomic measures are valid diagnostic and therapeutic outcome criteria for this situational phobia.

    View details for DOI 10.1037/0021-843X.114.1.126

    View details for Web of Science ID 000227146600013

    View details for PubMedID 15709819

  • Respiratory feedback for treating panic disorder JOURNAL OF CLINICAL PSYCHOLOGY Meuret, A. E., Wilhelm, F. H., Roth, W. T. 2004; 60 (2): 197-207


    Panic disorder patients often complain of shortness of breath or other respiratory complaints, which has been used as evidence for both hyperventilation and false suffocation alarm theories of panic. Training patients to change their breathing patterns is a common intervention, but breathing rarely has been measured objectively in assessing the patient or monitoring therapy results. We report a new breathing training method that makes use of respiratory biofeedback to teach individuals to modify four respiratory characteristics: increased ventilation (Respiratory Rate x Tidal Volume), breath-to-breath irregularity in rate and depth, and chest breathing. As illustrated by a composite case, feedback of respiratory rate and end-tidal pCO2 can facilitate voluntary control of respiration and reduce symptoms. Respiratory monitoring may provide relevant diagnostic, prognostic, and outcome information.

    View details for DOI 10.1002/jclp.10245

    View details for Web of Science ID 000188430200007

    View details for PubMedID 14724927

  • The LifeShirt - An advanced system for ambulatory measurement of respiratory and cardiac function BEHAVIOR MODIFICATION Wilhelm, F. H., Roth, W. T., Sackner, M. A. 2003; 27 (5): 671-691


    An accurate ambulatory breathing monitor is needed to observe acute respiratory changes in patients with medical or psychological disorders outside the clinic (e.g., hyperventilation during panic or apneas during sleep). Significant limitations of existing monitors are size, troublesome operation, and difficulty holding chest and abdomen bands in place during 24-hour recordings. Recently, a garment has been developed with embedded inductive plethysmography sensors for continuous ambulatory monitoring of respiration, heart activity, inductive cardiography, motility, postural changes, and other functions. The signals are displayed and stored on a handheld computer (Visor), and then analyzed offline, extracting more than 40 clinical parameters relating to cardiorespiratory function (e.g., heart rate, respiratory sinus arrhythmia, tidal volume, stroke volume, pre-ejection period, apnea-hypopnea index, thoraco-abdominal coordination, sighing). The device also serves as an electronic diary of symptoms, moods, and activities. This advanced system may open a new era in ambulatory monitoring for clinical practice and scientific research.

    View details for DOI 10.1177/0145445503256321

    View details for Web of Science ID 000185192800006

    View details for PubMedID 14531161

  • Breathing training for treating panic disorder - Useful intervention or impediment? BEHAVIOR MODIFICATION Meuret, A. E., Wilhelm, F. H., Ritz, T., Roth, W. T. 2003; 27 (5): 731-754


    Breathing training (BT) is commonly used for treatment of panic disorder. We identified nine studies that reported the outcome of BT. Overall, the published studies of BT are not sufficiently compelling to allow an unequivocal judgment of whether such techniques are beneficial. This article discusses problems with the underlying rationale, study design, and techniques used in BT, and it identifies factors that may have determined therapy outcomes. The idea that hypocapnia and respiratory irregularities are underlying factors in the development of panic implies that these factors should be monitored physiologically throughout therapy. Techniques taught in BT must take account of respiration rate and tidal volume in the regulation of blood gases (pCO2). More studies are needed that are designed to measure the efficacy of BT using an adequate rationale and methodology. Claims that BT should be rejected in favor of cognitive or other forms of intervention are premature.

    View details for DOI 10.1177/0145445503256324

    View details for Web of Science ID 000185192800009

    View details for PubMedID 14531164

  • Salivary cortisol response during exposure treatment in driving phobics PSYCHOSOMATIC MEDICINE Alpers, G. W., Abelson, J. L., Wilhelm, F. H., Roth, W. T. 2003; 65 (4): 679-687


    Extensive research on the hypothalamic-pituitary-adrenal (HPA) axis response to stress has not clarified whether that axis is activated by phobic anxiety. We addressed this issue by measuring cortisol in situational phobics during exposure treatment.Salivary cortisol was measured in 11 driving phobics before and during three exposure sessions involving driving on crowded limited-access highways and compared with levels measured in 13 healthy controls before and during two sessions of driving on the same highways. For each subject, data collected in the same time period on a comparison nondriving day served as an individual baseline from which cortisol response scores were calculated.Cortisol levels of driving phobics and controls did not differ on the comparison day. Phobics also had normal cortisol response scores on awakening on the mornings of the exposures but these were already increased 1 hour before coming to the treatment sessions. Phobics had significantly greater cortisol response scores during driving exposure and during quiet sitting periods before and afterward. These greater responses generally paralleled increases in self-reported anxiety. At the first exposure session, effect sizes for differences in cortisol response scores between the two groups were large. Initial exposure to driving in the first session evoked the largest responses.The data demonstrate that the HPA axis can be strongly activated by exposure to, and anticipation of, a phobic situation.

    View details for DOI 10.1097/01.PSY.0000073872.85623.0C

    View details for Web of Science ID 000184362200030

    View details for PubMedID 12883122

  • Predictors of response in anxiety disorders PSYCHIATRIC CLINICS OF NORTH AMERICA Solvason, H. B., ERNST, H., Roth, W. 2003; 26 (2): 411-?


    Anxiety disorder variables such as duration, severity of illness, and comorbidity with other anxiety or mood disorders appear to identify individuals who are at the greatest risk of treatment nonresponse. Conversely, in accord with clinical experience, shorter periods of illness, less severe illness, being treatment naive, and the absence of comorbidity tend to identify patients who are likely to respond robustly to medication management. Symptom clusters in OCD and PTSD are promising as a means of stratifying those more likely to respond to standard pharmacologic treatment. The presence of hoarding or sexual obsessions seems to presage poorer response in OCD, while the presence of dissociative symptoms in PTSD has been linked to high nonspecific treatment response rates to placebo. Genotyping individuals with respect to genes that are thought to have an important role in the underlying disease process, such as the work with the 5HTTL-PR allele, is exciting and is perhaps the first glimmer of using genotyping to identify treatment strategies or to predict the likelihood or speed of response. The use of neuroimaging as a means of identifying individuals who may respond favorably to pharmacologic or neurosurgical intervention is still in its infancy. As a strategy, it may help combine symptom severity and response variables into a clear neurobiologic vulnerability model of illness. In the future, it may be possible to identify specific treatment interventions for specific patterns of abnormal metabolic rates in certain areas of the brain. However, it should be emphasized that such an approach has not been empirically demonstrated in a rigorous experimental context at this time.

    View details for DOI 10.1016/S0193-953X(03)00027-3

    View details for Web of Science ID 000182929300008

    View details for PubMedID 12778841

  • Detection of speaking with a new respiratory inductive plethysmography system BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 39 Wilhelm, F. H., Handke, E. M., Roth, W. T. 2003; 39: 136-141


    The LifeShirt system, a garment with integrated sensors connected to a handheld computer, allows recording of a wide variety of clinically important cardiorespiratory data continuously for extended periods outside the laboratory or clinic. The device includes sensors for assessment of physical activity and posture since both can affect physiological activation and need to be controlled. Speaking is another potential confounding factor in the interpretation of physiological data. Auditory speech recording is problematic because it can pick up sources other than the person's voice (external microphone) or is obtrusive (throat microphone). The abdominal and thoracic calibrated respiratory inductive plethysmography (RIP) sensors integrated in the LifeShirt system might be an adequate alternative for detecting speech. In a laboratory experiment we determined respiratory parameters indicative of speech. Eighteen subjects were instructed to sit quietly, write, and speak continuously, for 4 min each. Nine parameters were derived from the RIP signals and averaged over each minute. In addition, nine variability parameters were computed as their coefficients of breath-by-breath variation. Inspiratory/expiratory time (IE-ratio) best distinguished speaking from writing with 98% correct classification at a cutoff criterion of 0.52. This criterion was equally successful in distinguishing speaking from sitting quietly. Discriminant analyses indicated that linear combinations of IE-ratio and a variety of other parameters did not reliably improve classification accuracy across tasks and replications. These results demonstrate the high efficacy of RIP-derived IE-ratio for speech detection and suggest that auditory recording is not necessary for detection of speech in ambulatory assessment.

    View details for Web of Science ID 000182321800024

    View details for PubMedID 12724882

  • Embarrassment and social phobia: the role of parasympathetic activation JOURNAL OF ANXIETY DISORDERS Gerlach, A. L., Wilhelm, F. H., Roth, W. T. 2003; 17 (2): 197-210


    The few studies on the psychophysiology of embarrassment have suggested involvement of parasympathetic activation. However, blushing, the hallmark of embarrassment and a prominent symptom in social phobia, is more likely to be produced by cervical sympathetic outflow. Hitherto, there has been no evidence of parasympathetic innervation of the facial blood vessels. In this study, a group of social phobics and control participants watched, together with a 2-person audience, a previously made videotape of themselves singing a children's song. Self-report measures confirmed that this task induced embarrassment. While two measures of respiratory sinus arrhythmia (RSA) during the task did not indicate heightened parasympathetic tone, increased heart rate (HR) and skin conductance marked sympathetic activation. Thus, our data do not support the notion that an increase in parasympathetic activation plays a significant role in social phobia and embarrassment. Social anxiety and embarrassment both resulted in sympathetic activation.

    View details for Web of Science ID 000181646200005

    View details for PubMedID 12614662

  • Reduced communication between frontal and temporal lobes during talking in schizophrenia BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Whitfield, S., Faustman, W. O., Roth, W. T. 2002; 51 (6): 485-492


    Communication between the frontal lobes, where speech and verbal thoughts are generated, and the temporal lobes, where they are perceived, may occur through the action of a corollary discharge. Its dysfunction may underlie failure to recognize inner speech as self-generated and account for auditory hallucinations in schizophrenia.Electroencephalogram was recorded from 10 healthy adults and 12 patients with schizophrenia (DSM-IV) in two conditions: talking aloud and listening to their own played-back speech. Event-related electroencephalogram coherence to acoustic stimuli presented during both conditions was calculated between frontal and temporal pairs, for delta, theta, alpha, beta, and gamma frequency bands.Talking produced greater coherence than listening between frontal-temporal regions in all frequency bands; however, in the lower frequencies (delta and theta), there were significant interactions of group and condition. This finding revealed that patients failed to show an increase in coherence during talking, especially over the speech production and speech reception areas of the left hemisphere, and especially in patients prone to hallucinate.Reduced fronto-temporal functional connectivity may contribute to the misattribution of inner thoughts to external voices in schizophrenia.

    View details for Web of Science ID 000174739000008

    View details for PubMedID 11922884

  • High altitudes, anxiety, and panic attacks: Is there a relationship? DEPRESSION AND ANXIETY Roth, W. T., Gomolla, A., Meuret, A. E., Alpers, G. W., Handke, E. M., Wilhelm, F. H. 2002; 16 (2): 51-58


    People exposed to high altitudes often experience somatic symptoms triggered by hypoxia, such as breathlessness, palpitations, dizziness, headache, and insomnia. Most of the symptoms are identical to those reported in panic attacks or severe anxiety. Potential causal links between adaptation to altitude and anxiety are apparent in all three leading models of panic, namely, hyperventilation (hypoxia leads to hypocapnia), suffocation false alarms (hypoxia counteracted to some extent by hypocapnia), and cognitive misinterpretations (symptoms from hypoxia and hypocapnia interpreted as dangerous). Furthermore, exposure to high altitudes produces respiratory disturbances during sleep in normals similar to those in panic disorder at low altitudes. In spite of these connections and their clinical importance, evidence for precipitation of panic attacks or more gradual increases in anxiety during altitude exposure is meager. We suggest some improvements that could be made in the design of future studies, possible tests of some of the theoretical causal links, and possible treatment applications, such as systematic exposure of panic patients to high altitude.

    View details for DOI 10.1002/da.10059

    View details for Web of Science ID 000178260700001

    View details for PubMedID 12219335

  • Neurophysiological evidence of corollary discharge dysfunction in schizophrenia AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Heinks, T., Kalba, S., Faustman, W. O., Roth, W. T. 2001; 158 (12): 2069-2071


    Speaking is hypothesized to generate a corollary discharge of motor speech commands transmitted to the auditory cortex, dampening its response to self-generated speech sounds. Event-related potentials were used to test whether failures of corollary discharge during speech contribute to the pathophysiology of schizophrenia.The N1 component of the event-related potential elicited by vowels was recorded while the vowels were spoken by seven patients with schizophrenia and seven healthy comparison subjects and while the same vowels were played back.In the healthy subjects, the N1 elicited by spoken vowels was smaller than the N1 elicited by played-back vowels. This reduction in N1 elicited by spoken vowels was not observed in the patients with schizophrenia.These findings provide direct neurophysiological evidence for a corollary discharge that dampens sensory responses to self-generated, relative to externally presented, percepts in healthy comparison subjects and its failure in patients with schizophrenia.

    View details for Web of Science ID 000172452100023

    View details for PubMedID 11729029

  • Cortical responsiveness during inner speech in schizophrenia: An event-related potential study AMERICAN JOURNAL OF PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 158 (11): 1914-1916


    The study assessed the effects of inner speech on auditory cortical responsiveness in schizophrenia.Comparison subjects (N=15) and patients with schizophrenia (N=15) were presented with acoustic and visual stimuli during three conditions: while subjects were silent, when spontaneous inner speech might occur; during directed inner speech, while subjects repeated a statement silently to themselves; and while subjects listened to recorded speech. N1 event-related potentials were recorded during the three conditions.N1 event-related potentials elicited by acoustic stimuli, but not by visual stimuli, were lower during directed inner speech than during the silent baseline condition in the comparison subjects but not in the patients.Abnormal auditory cortical responsiveness to inner speech in patients with schizophrenia may be a sign of corollary discharge dysfunction, which may potentially cause misattribution of inner speech to external voices.

    View details for Web of Science ID 000171946300022

    View details for PubMedID 11691701

  • Cortical responsiveness during talking and listening in schizophrenia: An event-related brain potential study BIOLOGICAL PSYCHIATRY Ford, J. M., Mathalon, D. H., Kalba, S., Whitfield, S., Faustman, W. O., Roth, W. T. 2001; 50 (7): 540-549


    Failures to recognize inner speech as self-generated may underlie positive symptoms of schizophrenia-like auditory hallucinations. This could result from a faulty comparison in auditory cortex between speech-related corollary discharge and reafferent discharges from thinking or speaking, with misattribution of internal thoughts to external sources. Although compelling, failures to monitor covert speech (thoughts) are not as amenable to investigation as failures to monitor overt speech (talking).Effects of talking on auditory cortex responsiveness were assessed in 10 healthy adults and 12 patients with schizophrenia (DSM-IV) using N1 event-related potentials (ERPs) to acoustic and visual probes during talking aloud, listening to one's speech played back, and silent baseline. Trials contaminated by muscle artifact while talking were excluded.Talking and listening affected N1 to acoustic but not to visual probes, reflecting modality specificity of effects. Patterns of responses to acoustic probes differed between control subjects and patients. N1 to acoustic probes was reduced during talking compared with baseline in control subjects, but not in patients. Listening reduced N1 equivalently in both groups.Although the failure of N1 to be reduced during talking was not related to current hallucinations in patients, it may be related to the potential to hallucinate.

    View details for Web of Science ID 000171582200008

    View details for PubMedID 11600107

  • Respiratory biofeedback-assisted therapy in panic disorder BEHAVIOR MODIFICATION Meuret, A. E., Wilhelm, F. H., Roth, W. T. 2001; 25 (4): 584-605


    The authors describe a new methodologically improved behavioral treatment for panic patients using respiratory biofeedback from a handheld capnometry device. The treatment rationale is based on the assumption that sustained hypocapnia resulting from hyperventilation is a key mechanism in the production and maintenance of panic. The brief 4-week biofeedback therapy is aimed at voluntarily increasing self-monitored end-tidal partial pressure of carbon dioxide (PCO2) and reducing respiratory rate and instability through breathing exercises in patients' environment. Preliminary results from 4 patients indicate that the therapy was successful in reducing panic symptoms and other psychological characteristics associated with panic disorder. Physiological data obtained from home training, 24-hour ambulatory monitoring pretherapy and posttherapy, and laboratory assessment at follow-up indicate that patients started out with low resting PCO2 levels, increased those levels during therapy, and maintained those levels at posttherapy and/or follow-up. Partial dissociation between PCO2 and respiratory rate questions whether respiratory rate should be the main focus of breathing training in panic disorder.

    View details for Web of Science ID 000170514300006

    View details for PubMedID 11530717

  • Respiratory dysregulation in anxiety, functional cardiac, and pain disorders - Assessment, phenomenology, and treatment BEHAVIOR MODIFICATION Wilhelm, F. H., Gevirtz, R., Roth, W. T. 2001; 25 (4): 513-545


    Respiration is a complex physiological system affecting a variety of physical processes that can act as a critical link between mind and body. This review discusses the evidence for dysregulated breathing playing a role in three clinical syndromes: panic disorder, functional cardiac disorder, and chronic pain. Recent technological advances allowing the ambulatory assessment of endtidal partial pressure of CO2 (PCO2) and respiratory patterns have opened up new avenues for investigation and treatment of these disorders. The latest evidence from laboratories indicates that subtle disturbances of breathing, such as tidal volume instability and sighing, contribute to the chronic hypocapnia often found in panic patients. Hypocapnia is also common in functional cardiac and chronic pain disorders, and studies indicate that it mediates some of their symptomatology. Consistent with the role of respiratory dysregulation in these disorders, initial evidence indicates efficacy of respiration-focused treatment.

    View details for Web of Science ID 000170514300003

    View details for PubMedID 11530714

  • Slow recovery from voluntary hyperventilation in panic disorder PSYCHOSOMATIC MEDICINE Wilhelm, F. H., Gerlach, A. L., Roth, W. T. 2001; 63 (4): 638-649


    Because hyperventilation has figured prominently in theories of panic disorder (PD) but not of social phobia (SP), we compared predictions regarding diagnosis-specific differences in psychological and physiological measures before, during, and after voluntary hyperventilation.Physiological responses were recorded in 14 patients with PD, 24 patients with SP, and 24 controls during six cycles of 1-minute of fast breathing alternating with 1 minute of recovery, followed by 3 minutes of fast breathing and 10 minutes of recovery. Speed of fast breathing was paced by a tone modulated at 18 cycles/minute, and depth by feedback aimed at achieving an end-tidal pCO2 of 20 mm Hg. These values were reached equally by all groups.During fast breathing, PD and SP patients reported more anxiety than controls, and their feelings of dyspnea and suffocation increased more from baseline. Skin conductance declined more slowly in PD over the six 1-minute fast breathing periods. At the end of the final 10-minute recovery, PD patients reported more awareness of breathing, dyspnea, and fear of being short of breath, and their pCO2s, heart rates, and skin conductance levels had returned less toward normal levels than in other groups. Their lower pCO2s were associated with a higher frequency of sigh breaths.PD and SP patients report more distress than controls to equal amounts of hypocapnia, but PD differ from SP patients and controls in having slower symptomatic and physiological recovery. This finding was not specifically predicted by hyperventilation, cognitive-behavioral, or suffocation alarm theories of PD.

    View details for Web of Science ID 000170119800015

    View details for PubMedID 11485118

  • The somatic symptom paradox in DSM-IV anxiety disorders: suggestions for a clinical focus in psychophysiology BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 2001; 57 (1-3): 105-140


    Although DSM-IV criteria for anxiety disorders include physiological symptoms, these symptoms are evaluated exclusively by verbal report. The current review explores the background for this paradox and tries to demonstrate on theoretical and empirical grounds how it could be resolved, providing new insights about the role of psychophysiological measures in the clinic. The three-systems approach to evaluating anxiety argues that somatic measures as well as verbal and behavioral ones are indispensable. However, the low concordance between these domains of measurement impugns their reliability and validity. We argue that concordance can be improved by examining the relationship of variables less global than anxiety and by restriction to specific anxiety disorders. For example, recent evidence from our and other laboratories indicate a prominent role of self-reported and physiologically measured breathing irregularities in panic disorder. Nonetheless, even within a diagnosis, anxiety patients vary radically in which somatic variables are deviant. Thus, in clinical practice, individual profiles of psychological and physiological anxiety responses may be essential to indicate distinct therapeutic approaches and ways of tracking improvement. Laboratory provocations specific to certain anxiety disorders and advances in ambulatory monitoring vastly expand the scope of self-report and physiological measurement and will likely contribute to a refined assessment of anxiety disorders.

    View details for Web of Science ID 000170196500006

    View details for PubMedID 11454436

  • Blushing and physiological arousability in social phobia JOURNAL OF ABNORMAL PSYCHOLOGY Gerlach, A. L., Wilhelm, F. H., Gruber, K., Roth, W. T. 2001; 110 (2): 247-258


    Blushing is the most prominent symptom of social phobia, and fear perception of visible anxiety symptoms is an important component of cognitive behavioral models of social phobia. However, it is not clear how physiological and psychological aspects of blushing and other somatic symptoms are linked in this disorder. The authors tested whether social situations trigger different facial blood volume changes (blushing) between social phobic persons with and without primary complaint of blushing and control participants. Thirty social phobic persons. 15 of whom were especially concerned about blushing, and 14 control participants were assessed while watching an embarrassing videotape, holding a conversation, and giving a talk. Only when watching the video did the social phobic persons blush more than controls blushed. Social phobic persons who complained of blushing did not blush more intensely than did social phobic persons without blushing complaints but had higher heart rates, possibly reflecting higher arousability of this subgroup.

    View details for Web of Science ID 000170879900006

    View details for PubMedID 11358019

  • Physiologic instability in panic disorder and generalized anxiety disorder BIOLOGICAL PSYCHIATRY Wilhelm, F. H., Trabert, W., Roth, W. T. 2001; 49 (7): 596-605


    Because panic attacks can be accompanied by surges in physiologic activation, we tested the hypothesis that panic disorder is characterized by fluctuations of physiologic variables in the absence of external triggers.Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Electrodermal, cardiovascular, and respiratory measures were analyzed using complex demodulation to quantify variability in physiologic indices.Both patient groups reported equally more anxiety and cardiac symptoms than control subjects, but certain other somatic symptoms, including breathlessness, were elevated only in panic disorder patients. Mean end-tidal pCO(2) and respiratory rates were lower, and tidal volume and the number of sighs were higher in panic disorder patients than control subjects. Neither cardiovascular (heart rate, arterial pressure, cardiac output), nor electrodermal instability including sighs distinguished the groups; however, tidal volume instability was greater in panic disorder than generalized anxiety disorder patients or control subjects. Several other respiratory measures (pCO(2), respiratory rate, minute volume, duty cycle) showed greater instability in both patient groups than in control subjects.Respiration is particularly unstable in panic disorder, underlining the importance of respiratory physiology in understanding this disorder. Whether our findings represent state or trait characteristics is discussed.

    View details for Web of Science ID 000167899700006

    View details for PubMedID 11297717

  • Characteristics of sighing in panic disorder BIOLOGICAL PSYCHIATRY Wilhelm, F. H., Trabert, W., Roth, W. T. 2001; 49 (7): 606-614


    Sighs, breaths with larger tidal volumes than surrounding breaths, have been reported as being more frequent in patients with anxiety disorders.Sixteen patients with panic disorder, 15 with generalized anxiety disorder, and 19 normal control subjects were asked to sit quietly for 30 min. Respiratory volumes and timing were recorded with inductive plethysmography and expired pCO(2), from nasal prongs.Panic disorder patients sighed more and had tonically lower end-tidal pCO(2)s than control subjects, whereas generalized anxiety disorder patients were intermediate. Sighs defined as >2.0 times the subject mean discriminated groups best. Sigh frequency was more predictive of individual pCO(2) levels than was minute volume. Ensemble averaging of respiratory variables for sequences of breaths surrounding sighs showed no evidence that sighs were triggered by increased pCO(2) or reduced tidal volume in any group. Sigh breaths were larger in panic disorder patients than in control subjects. After sighs, pCO(2) and tidal volume did not return to baseline levels as quickly in panic disorder patients as in control subjects.Hypocapnia in panic disorder patients is related to sigh frequency. In none of the groups was sighing a homeostatic response. Panic disorder patients show less peripheral chemoreflex gain than control subjects, which would maintain low pCO(2) levels after sighing.

    View details for Web of Science ID 000167899700007

    View details for PubMedID 11297718

  • Failures of automatic and strategic processing in schizophrenia: comparisons of event-related brain potential and startle blink modification SCHIZOPHRENIA RESEARCH Ford, J. M., Roth, W. T., Menon, V., Pfefferbaum, A. 1999; 37 (2): 149-163


    Noises elicit startle blinks that are inhibited when immediately (approximately 100 ms) preceded by non-startling prepulses, perhaps reflecting automatic sensory gating. Startle blinks are facilitated when preceded by prepulses at longer lead intervals, perhaps reflecting strategic processes. Event-related brain potentials (ERPs) and startle blinks were used to investigate the well-documented prepulse inhibition failure in schizophrenia. Blinks and ERPs were recorded from 15 schizophrenic men and 20 age-matched controls to noises alone and to noises preceded by prepulses at 120 (PP120), 500 (PP500) and 4000 ms (PP4000) lead intervals. Neither blinks nor any of the ERP components elicited by the noise alone differentiated schizophrenics from controls, although responses to noises were modified by prepulses differently in the two groups. With the N1 component of the ERP, patients showed normal inhibition but lacked facilitation, and with P2, patients lacked inhibition, but showed normal facilitation. With reflex blinks and P300, inhibition was seen in both groups, but no facilitation. These results suggest that different neural circuits are involved in blink and cortical reflections of startle modification in schizophrenics and controls, with both automatic and strategic processes being impaired in schizophrenia.

    View details for Web of Science ID 000080583700003

    View details for PubMedID 10374650

  • Analysis of cardiovascular regulation. Biomedical sciences instrumentation Wilhelm, F. H., Grossman, P., Roth, W. T. 1999; 35: 135-140


    Adequate characterization of hemodynamic and autonomic responses to physical and mental stress can elucidate underlying mechanisms of cardiovascular disease or anxiety disorders. We developed a physiological signal processing system for analysis of continuously recorded ECG, arterial blood pressure (BP), and respiratory signals using the programming language Matlab. Data collection devices are a 16-channel digital, physiological recorder (Vitaport), a finger arterial pressure transducer (Finapres), and a respiratory inductance plethysmograph (Respitrace). Besides the conventional analysis of the physiological channels, power spectral density and transfer functions of respiration, heart rate, and blood pressure variability are used to characterize respiratory sinus arrhythmia (RSA), 0.10-Hz BP oscillatory activity (Mayer-waves), and baroreflex sensitivity. The arterial pressure transducer waveforms permit noninvasive estimation of stroke volume, cardiac output, and systemic vascular resistance. Time trends in spectral composition of indices are assessed using complex demodulation. Transient dynamic changes of cardiovascular parameters at the onset of stress and recovery periods are quantified using a regression breakpoint model that optimizes piecewise linear curve fitting. Approximate entropy (ApEn) is computed to quantify the degree of chaos in heartbeat dynamics. Using our signal processing system we found distinct response patterns in subgroups of patients with coronary artery disease or anxiety disorders, which were related to specific pharmacological and behavioral factors.

    View details for PubMedID 11143335

  • Voluntary breath holding in panic and generalized anxiety disorders PSYCHOSOMATIC MEDICINE Roth, W. T., Wilhelm, F. H., Trabert, W. 1998; 60 (6): 671-679


    Because breath holding causes arterial pCO2 to increase, we used it to test the hypothesis that in panic disorder (PD) a biological suffocation monitor is pathologically sensitive.Nineteen patients with PD, 17 with generalized anxiety disorder (GAD), and 22 normal controls took deep breaths on signal and held them until a release signal was given 30 seconds later. This was repeated 12 times separated by 60-second normal breathing periods.PD patients reported having had in the past more symptoms of shortness of breath when anxious, and more frequent frightening suffocation experiences than the other groups. However, increases in self-rated anxiety between periods of normal breathing and periods of breath holding were similar in all three groups. Skin conductance, blood pressure, and T-wave amplitude reactions to breath holdings were also similar, but heart rate acceleration upon taking a deep breath was greater in GAD patients. Before and after individual breath holdings, end-tidal pCO2 was lower in PD patients than in normal controls; GAD patients were intermediate. Inspiratory flow rate did not differ between groups.Our physiological results provide no direct support for an overly sensitive suffocation alarm system in PD. Lower pCO2 may be due to anxiety causing hyperventilation in patients prone to panic.

    View details for Web of Science ID 000077189300003

    View details for PubMedID 9847025

  • Using minute ventilation for ambulatory estimation of additional heart rate BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 1998; 49 (1-2): 137-150


    Both physical activity and emotion produce physiological activation. The emotional component of heart rate (HR) can be estimated as the additional HR (aHR) above that predicted by O2 consumption. Our innovation was to substitute minute ventilation (V) for O2 consumption, calculating aHR from individual relations between V and HR during an exercise test. We physiologically monitored 28 flight phobics and 15 non-anxious controls while walking (leaving the hospital, entering a plane), and during a commercial flight. Raw HR did not differ between phobics and controls when leaving the hospital (118/114 bpm) or entering the plane (117/110 bpm). However, although aHR was not different when leaving the hospital (7.0/8.6 bpm), it was significantly greater when entering the plane (17.5/9.9 bpm), accurately reflecting the increased subjective anxiety of the phobics. V was not higher in phobics than controls during any condition, suggesting an absence of hyperventilation in the phobics. The results demonstrate the utility of our method for analyzing HR in people whose stress occurs when they are physically active.

    View details for Web of Science ID 000076545300010

    View details for PubMedID 9792490

  • Taking the laboratory to the skies: Ambulatory assessment of self-report, autonomic, and respiratory responses in flying phobia PSYCHOPHYSIOLOGY Wilhelm, F. H., Roth, W. T. 1998; 35 (5): 596-606


    We evaluated the feasibility of recording multiple physiological anxiety measures during a flight and how well they could distinguish flight phobics from controls. Benefits of baseline adjustment and transformation for all variables and adjustment of heart rate by ventilation to give additional heart rate were calculated. Effect size, one measure of the power to discriminate groups, was between 1.1 and 1.7 for heart rate measures. Although respiratory rate and minute ventilation, indicators of hyperventilation, did not differ between groups, phobics paused more during inspiration than did controls. Phobics also showed more skin conductance fluctuations and less respiratory sinus arrhythmia. Self-reported anxiety was a more powerful discriminator than physiological measures, a result that may be partially explained by how phobics were selected. These results indicate that monitoring of multiple physiological systems outside the laboratory is practical and informative. Physiological measures of psychological importance can be quantified accurately in a noisy, changing, unsupervised ambulatory setting.

    View details for Web of Science ID 000075303100012

    View details for PubMedID 9715103

  • Critique - Trusting computerized data reduction too much: A critique of Anderson's ambulatory respiratory monitor BIOLOGICAL PSYCHOLOGY Wilhelm, F. H., Roth, W. T. 1998; 49 (1-2): 215-219

    View details for Web of Science ID 000076545300014

    View details for PubMedID 9792494

  • Autonomic instability during relaxation in panic disorder PSYCHIATRY RESEARCH Roth, W. T., Wilhelm, F. H., Trabert, W. 1998; 80 (2): 155-164


    The ability to relax was assessed in 14 patients with panic disorder (PD) and 15 non-anxious control subjects for 10 min. Before and after relaxation, subjects performed a standardized activating task of talking continuously for 4 min. The fractional decline in reported anxiety, tension, and alertness between the first talking period and the relaxation minimum did not differ between groups, although absolute levels of anxiety and tension were higher for PD patients. The fractional decline in skin conductance between the first talking period and the last minute of relaxation was less for PD patients than control subjects, while their increase in skin temperature was greater. Skin conductance showed a linear decline over the logarithm of relaxation time, the slope of which was less steep for PD patients. Goodness of fit of skin conductance over log time was also significantly poorer for PD patients. Heart rate levels or slopes did not differ between groups. Autonomic differences between PD and control subjects were largely due to six patients who reported having panic attacks during the test and higher pretest anxiety levels. In conclusion, indicators of relaxation were inconsistent. Skin conductance suggested autonomic instability during quiet sitting in patients who panic or who are prone to panic.

    View details for Web of Science ID 000075876300007

    View details for PubMedID 9754695

  • Speech disturbances and gaze behavior during public speaking in subtypes of social phobia JOURNAL OF ANXIETY DISORDERS Hofmann, S. G., Gerlach, A. L., Wender, A., Roth, W. T. 1997; 11 (6): 573-585


    Twenty-four social phobics with public speaking anxiety and 25 nonphobic individuals (controls) gave a speech in front of two people. Subjective anxiety, gaze behavior, and speech disturbances were assessed. Based on subjects' fear ratings of social situations, phobics and controls were divided into the generalized and nongeneralized subtype. Results showed that generalized phobics reported the most, and nongeneralized controls the least anxiety during public speaking. All subjects had longer and more frequent eye contact when delivering a speech than when talking with an experimenter or sitting in front of an audience. Phobics showed more filled pauses, had longer silent pauses, paused more frequently, and spent more time pausing than controls when giving a speech. Generalized phobics spent more time pausing during their speech than the other subgroups (nongeneralized controls, generalized controls, and nongeneralized phobics). These results suggest that generalized phobics tended to shift attentional resources from speech production to other cognitive tasks.

    View details for Web of Science ID 000071540800002

    View details for PubMedID 9455720

  • Acute and delayed effects of alprazolam on flight phobics during exposure BEHAVIOUR RESEARCH AND THERAPY Wilhelm, F. H., Roth, W. T. 1997; 35 (9): 831-841


    In order to test if a benzodiazepine would enhance or hinder the therapeutic effects of exposure, immediate and delayed effects of alprazolam on flight phobics were assessed by questionnaires and ambulatory physiological recording. Physiological measures included heart rate, skin conductance level and fluctuations, finger temperature, respiratory sinus arrhythmia, and various respiratory measures derived from two bands calibrated for each subject. Twenty-eight women with flying phobia flew twice at a 1-week interval. One and a half hours before flight 1, 14 randomly assigned phobics received double-blind 1 mg of alprazolam and 14 received placebo. On flight 1, alprazolam reduced self-reported anxiety (5.0 vs 7.4) and symptoms (5.3 vs 3.6) more than placebo, but induced an increase in heart rate (114 vs 105 bpm) and respiratory rate (22.7 vs 18.3 breaths/min). Before flight 2, the alprazolam group did not expect to be more anxious than the placebo group (6.7 vs 6.5), but in fact indicated more anxiety during flight (8.5 vs 5.6), and a substantial increase in panic attacks from flight 1 to flight 2 (7% vs 71%). Heart rates in the alprazolam group increased further (123 bpm). Results indicate that alprazolam increases physiological activation under acute stress conditions and hinders therapeutic effects of exposure in flying phobia.

    View details for Web of Science ID A1997XR87500005

    View details for PubMedID 9299803

  • Clinical characteristics of flight phobia JOURNAL OF ANXIETY DISORDERS Wilhelm, F. H., Roth, W. T. 1997; 11 (3): 241-261


    Sixty-six subjects with severe fear of flying were recruited by advertisement and compared to 21 controls without flying fears. Subjects were interviewed and given several questionnaires to determine DSM-III-R diagnoses, history of flying, and development and course of flying phobia. Our phobic sample had a mean age of 46 and was 89% female. Diagnostically, 27% met criteria for current Panic Disorder with Agoraphobia, and 17% criteria for that diagnosis in the past. These two groups were more concerned with internal or social anxiety stimuli during flight than the group who had never had panic attacks but met criteria for Simple Phobia (flying). All three groups were equally concerned about external dangers. Traumatic flight events were common in phobics and controls, but phobics reported reacting to these events more strongly. Our results suggest a vulnerability-stress model with several vulnerability factors, including cognitive ones. Treatment implications are discussed.

    View details for Web of Science ID A1997XG50100002

    View details for PubMedID 9220299

  • Activation in novice and expert parachutists while jumping PSYCHOPHYSIOLOGY Roth, W. T., Breivik, G., Jorgensen, P. E., Hofmann, S. 1996; 33 (1): 63-72


    Heart and respiration rates were measured ambulatorily in 16 novice and 25 expert (> 380 delayed free-fall jumps) sports parachutists while making a static-line jump. Self-reported anxiety and heart rate peaked near the point of jumping in both groups rather than earlier in experts, as reported by Fenz and Epstein (1967, Psychosomatic Medicine, 29, 33-51). While sitting in the airplane 1 min before exit, mean heart rate was 124 bpm in novices and 102 in experts and increased during jumping to 170 and 145, respectively. The almost identical rise in the two groups could be accounted for largely by physical exertion, replicated with jumps from a training model on the ground. Exercise testing at a different location showed that experts were more fit. Respiration rate was higher in the airplane than at baselines, especially for novices. In conclusion, our results are more compatible theoretically with extinction of anticipatory anxiety than with learned anxiety inhibition.

    View details for Web of Science ID A1996TM04800007

    View details for PubMedID 8570796



    Individuals meeting criteria of the revised third edition of Diagnostic and Statistical Manual for Mental Disorders (American Psychiatric Association, 1987) for social phobia with a fear of speaking in front of people were subdivided into those with (n = 16) and without (n = 14) avoidant personality disorder (APD). These individuals and nonanxious controls (n = 22) spoke in front of a small audience while speaking time, subjective anxiety, fearful thoughts, and electrocardiographic and respiratory measures were recorded. Controls spoke for longer than either social phobia group. Those with social phobia and APD reported more subjective anxiety and more fear cognitions than the other two groups; phobic individuals without APD showed greater heart rates in the phobic situation than either social phobics with APD or controls. The latter two groups did not differ in heart rate. These results indicate incongruent subjective and heart rate responses to the feared situation. A similar pattern of results was found when participants were divided into generalized and specific social phobia groups.

    View details for Web of Science ID A1995QD42800025

    View details for PubMedID 7897046



    Seventy-nine patients with panic disorder were randomized to an 8-week double-blind treatment with alprazolam, imipramine, or placebo. Patients kept daily records of panic attacks, activity, anxiety, sleep, and medication use. Weekly measures of anxiety, depression, somatic symptoms, fears, avoidance, disability, and improvement were obtained. All patients underwent a symptom-limited exercise treadmill and other cardiovascular measures. By physician and patient global assessment, patients receiving alprazolam or imipramine were significantly better than patients on placebo. The alprazolam effects were apparent by week 1; the imipramine effects by week 4. All groups showed significant reductions in anxiety, depression, somatic measures, and panic attack frequency. At 8 weeks, patients in the alprazolam group reported significantly less fear than patients in the other two groups. Subjects in the imipramine group showed a significant increase in heart rate and blood pressure.

    View details for Web of Science ID A1990CX84900006

    View details for PubMedID 2187912

  • SURREPTITIOUS DRUG-USE BY PATIENTS IN A PANIC DISORDER STUDY AMERICAN JOURNAL OF PSYCHIATRY Clark, D. B., Taylor, C. B., Roth, W. T., Hayward, C., Ehlers, A., MARGRAF, J., Agras, W. S. 1990; 147 (4): 507-509


    In a double-blind, placebo-controlled trial comparing alprazolam and imipramine for panic disorder, serum analysis revealed that a substantial proportion of the patients took explicitly prohibited anxiolytic medication. Excluding these patients changed the results.

    View details for Web of Science ID A1990CW81000023

    View details for PubMedID 1969248



    A survey of 794 subjects volunteering for studies of panic disorder with or without phobic avoidance revealed that fewer than 15% had received imipramine and fewer than 15% had undergone in vivo exposure, although the majority had engaged in some form of counseling and had used benzodiazepines. Subjects with spontaneous panic attacks reported more avoidance than subjects with situational attacks. One-half of the subjects were unemployed. The authors recommend wider use of the available effective treatments for panic disorder and phobic avoidance.

    View details for Web of Science ID A1989AX18500005

    View details for PubMedID 2817112



    Plasma lipids were measured in 102 subjects with panic disorder or agoraphobia. In women, but not men, a significantly higher than expected number of subjects had cholesterol values that exceeded the 75th percentile of national reference values for their sex and age.

    View details for Web of Science ID A1989AD14300020

    View details for PubMedID 2742017



    Twenty patients with panic attacks and ten controls were given a standardised interview about thoughts occurring during times of anxiety or panic attacks. The interviewer was blind to the subject's diagnosis. The 20 panic patients underwent a psychophysiological test battery which included a cold pressor test, mental arithmetic task, and 5.5% CO2 inhalation. More patients than controls reported thoughts centered on fears of losing control and shame when anxious. Panic patients rated their thoughts as stronger and clearer than did controls and they had more difficulty excluding them from their minds. A feeling of anxiety preceded anxious thoughts in patients. This suggests that 'faulty cognitions' are not the initial event in a panic attack, although anxious thoughts may exacerbate or maintain them. Significant correlations were found between the intensity of anxiety-related thoughts in anticipation of mental arithmetic and changes in diastolic blood pressure and heart rate during mental arithmetic.

    View details for Web of Science ID A1989AJ61700013

    View details for PubMedID 2605437



    Twenty-three patients meeting DSM-III criteria for agoraphobia with panic attacks and 14 age-, race-, and sex-matched nonanxious controls were tested in the laboratory and on a test walk in a shopping mall. The patients were tested before and after about 15 weeks of treatment with placebo and exposure therapy, imipramine and exposure therapy, or imipramine and initial antiexposure instructions. Controls were tested twice at a similar interval, but without any treatment. On test day 1, patients compared to controls showed higher average heart rate and skin conductance levels and greater numbers of skin conductance fluctuations in the laboratory, and higher heart rates before and during the test walk. Between pretreatment and posttreatment tests, clinical ratings improved and skin conductance levels decreased in all treatment groups. Heart rate levels in the laboratory, on the other hand, decreased in patients on placebo and rose in patients on imipramine. Thus, imipramine compromises the usefulness of heart rate as a measure of emotional arousal. Higher pretreatment heart rates predicted greater clinical improvement.

    View details for Web of Science ID A1988N420300012

    View details for PubMedID 3393620

  • Treadmill exercise test and ambulatory measures in panic attacks. American journal of cardiology Taylor, C. B., King, R., Ehlers, A., MARGRAF, J., Clark, D., Hayward, C., Roth, W. T., Agras, S. 1987; 60 (18): 48J-52J


    Treadmill exercise test performance and ambulatory heart rate and activity patterns of 40 patients with panic attacks were compared with 20 age-matched controls (control group 1) and 20 nonexercising controls (control group 2). All patients underwent a symptom-limited exercise stress test. Panic attack patients and control group 1 wore an ambulatory heart rate/activity monitor for up to 3 days. Panic patients had a significantly higher heart rate at 4 and 6 METS than either control group. The max METS were 11.2 +/- 2.3, 13.5 +/- 2.3 and 11.2 +/- 1.8 for the panic attack patients and control groups 1 and 2, respectively. One panic patient had ischemia on the treadmill at 12 METS. Panic patients had a significantly higher standing heart rate than controls. Furthermore, 11 of 39 panic patients had tachycardia on standing compared with 3 of 40 controls. Panic attack patients had higher wake and sleep heart rates than control group 1, but the differences were not significant. These results are consistent with autonomic dysfunction in panic patients but may also be due to differences in physical conditioning. The treadmill can be useful for reassuring patients and for identifying the rare patient with ischemia on exercise.

    View details for PubMedID 3425557

Conference Proceedings

  • Affective computing: uSing computational intelligence techniques to classify the psychophysiological signatures of fearful, sad, and calm affective states Wilhelm, F. H., Kolodyazhniy, V., Kreibig, S. D., Roth, W. T., Gross, J. J. WILEY-BLACKWELL. 2007: S110-S111
  • Social anxiety and response to touch: incongruence between self-evaluative and physiological reactions Wilhelm, F. H., Kochar, A. S., Roth, W. T., Gross, J. J. ELSEVIER SCIENCE BV. 2001: 181-202


    Touch is an important form of social interaction, and one that can have powerful emotional consequences. Appropriate touch can be calming, while inappropriate touch can be anxiety provoking. To examine the impact of social touching, this study compared socially high-anxious (N=48) and low-anxious (N=47) women's attitudes concerning social touch, as well as their affective and physiological responses to a wrist touch by a male experimenter. Compared to low-anxious participants, high-anxious participants reported greater anxiety to a variety of social situations involving touch. Consistent with these reports, socially anxious participants reacted to the experimenter's touch with markedly greater increases in self-reported anxiety, self-consciousness, and embarrassment. Physiologically, low-anxious and high-anxious participants showed a distinct pattern of sympathetic-parasympathetic coactivation, as reflected by decreased heart rate and tidal volume, and increased respiratory sinus arrhythmia, skin conductance, systolic/diastolic blood pressure, stroke volume, and respiratory rate. Interestingly, physiological responses were comparable in low and high-anxious groups. These findings indicate that social anxiety is accompanied by heightened aversion towards social situations that involve touch, but this enhanced aversion and negative-emotion report is not reflected in differential physiological responding.

    View details for Web of Science ID 000172496600001

    View details for PubMedID 11698114

  • ELDERLY MEN AND WOMEN ARE LESS RESPONSIVE TO STARTLING NOISES - N1, P3 AND BLINK EVIDENCE Ford, J. M., Roth, W. T., Isaacks, B. G., White, P. M., Hood, S. H., Pfefferbaum, A. ELSEVIER SCIENCE BV. 1995: 57-80


    Previously we observed that the P3 component of the event-related brain potential (ERP) elicited by startling noises, and to a lesser extent P3 to target tones, is reduced in the elderly (Ford & Pfefferbaum, 1991). In the current experiment, we tried to eliminate possible effects of age-related hearing deficits on the responses to noises by filtering them to include only frequencies heard best by the elderly (0-1000 Hz) and by setting noise intensity relative to each subject's threshold (sensation level, SL). Twelve younger (mean 22 years) and 12 older (mean 69 years) men and women listened to three sequences of tones (80%, 500 Hz, 70 dB SPL) and noises (20%). One type of noise occurred in each sequence (wide band noise set to 107 dB SPL, narrow band noise set to 107 dB SPL, or narrow band noise set to approximately 65 dB SL). The order of the three sequences was counterbalanced across age and sex. Younger subjects blinked to the noise 4-5 times more often than older subjects and had N1 and P3 amplitudes that were 2-3 times larger, regardless of the noise type. N1 amplitude to the background frequent tones and non-startle blinks did not differ between groups. Thus, even when noises were narrow band and set relative to each subject's threshold, older subjects were less responsive to startling auditory stimuli than were younger.

    View details for Web of Science ID A1995QE66900001

    View details for PubMedID 7734630

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