Anxiety Disorders: Stanford University

Schatzberg AF. · Stanford University School of Medicine, California, USA. · CNS Spectr. · Pubmed #19317018 No free full text.

This publication has no abstract.

Beaudreau SA, O'Hara R. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Veterans Affairs Palo Alto Health Care System, Clinical Center (MIRECC), Palo Alto, CA 94304, USA. · Am J Geriatr Psychiatry. · Pubmed #18827225 No free full text.

Abstract: Emerging research implicates a consistent reciprocal relationship between late-life anxiety and cognition. Understanding this relationship may clarify pathophysiological substrates of cognitive impairment and why co-occurring anxiety and cognitive impairment relates to poorer treatment prognosis for both conditions. This article critically reviews evidence of more prevalent anxiety in cognitively impaired older adults, elevated anxiety related to poorer cognitive performance, and more severe anxiety symptoms predicting future cognitive decline. It considers pathophysiologic mediators and moderators, and the influence of comorbid depression or medical illness in anxiety. Identified directions for future research includes use of in-depth anxiety assessment comparing normal and mild cognitively impaired older adults and use of challenging neuropsychological tests to determine if specific cognitive domains suffer in anxious older adults.

Taylor CB, Chang VY. · Stanford University School of Medicine, Dept of Psychiatry & Behavioral Sciences, Stanford, CA 94305-5722, USA. · Nord J Psychiatry. · Pubmed #18752117 No free full text.

Abstract: In the past 40 years, cognitive-behavior therapy (CBT) has emerged as the initial treatment of choice for patients with mild to moderate depression, anxiety disorders and other problems. In this paper, we discuss issues related to the dissemination and implementation of CBT in various practice settings as well as the use of manuals, computers, the telephone, and the Internet to aid dissemination and implementation. We review key aspects of CBT dissemination, such as the reach of CBT, models of dissemination, and obstacles and barriers to dissemination including patient interest, therapist training and research priorities. The effectiveness of manualized programs is considered, as well as the increasing sophistication of computer-assisted therapy. Stepped-care approaches are discussed as a viable solution to some of these barriers. We provide two examples of successful CBT dissemination, the Staying Free program, a smoking cessation program for inpatients, and the Improving Access to Psychological Therapies program in Britain, which aims to improve access to psychological therapy. We argue that two critical factors will determine the success of implementation of CBT in this century: 1) mandated outcomes and 2) leadership.

Haas BW, Canli T. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA. · Brain Res Rev. · Pubmed #18359090 No free full text.

Abstract: It is well established that emotional events are ingrained stronger into memory relative to neutral events. Facilitated emotional memory is highly variable between individuals within the normal population and is particularly exacerbated in those diagnosed with mood and anxiety disorders. In order to elucidate how variation of enhanced emotional memory within the normal population may manifest into psychopathological states, we explored the convergence between studies investigating the neural systems engaged in emotional memory facilitation and studies investigating how these systems differ from person to person. Converging evidence highlights the roles of three neural systems (1. Amygdala function and attention, 2. Neuroendocrine function, 3. Interactive effects with mood) that all govern emotional memory facilitation and are highly variable between individuals as a function of personality. We applied this neural system approach to models of vulnerability of three forms of psychopathology that are particularly characterized by atypical emotional memory function (depression, generalized anxiety disorder and post-traumatic stress disorder). This application suggests that the incorporation of known vulnerability markers across psychological, neuroimaging and neuroendocrinological domains is cardinal to how susceptibility is conceptualized and assessed in these disorders.

Shaw RJ, Dayal S, Good J, Bruckner AL, Joshi SV. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305-5719, USA. · Psychosom Med. · Pubmed #17991825 No free full text.

Abstract: OBJECTIVES: To review the use of psychiatric medications in the treatment of pruritus. METHODS: A literature review was conducted using the key words pruritus, psychiatric, and treatment. RESULTS: Three categories of pruritus are described: dermatologic, systemic, and psychogenic. Peripheral and central nervous system mechanisms of pruritus are reviewed. Conventional dermatologic treatments for pruritus are contrasted with some of the common psychopharmacologic treatment modalities that include anxiolytic, antidepressant, and antipsychotic agents. A treatment algorithm is offered to help guide the treatment of patients with pruritus. CONCLUSIONS: Psychiatric medications have been used successfully in the treatment of pruritus that is associated with both psychocutaneous and systemic disorders, which are resistant to conventional treatment.

Thienemann M, Hamilton JD. · Division of Child Development and Child and Adolescent Psychiatry at Stanford University School of Medicine, USA. · J Am Acad Child Adolesc Psychiatry. · Pubmed #17885579 No free full text.

This publication has no abstract.

Lyons DM, Parker KJ. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, CA 94305-5485, USA. · J Trauma Stress. · Pubmed #17721972 No free full text.

Abstract: The negative consequences of stress are well-recognized in mental health research. Exposure to early life stressors, for example, increases the risk for the development of mood, anger, anxiety, and substance abuse disorders. Interestingly, however, early life stressors have also been linked to the subsequent development of resilience. Variously described as inoculating, immunizing, steeling, toughening, or thriving, the hypothesis that early life stressors provide a challenge that, when overcome, induces adaptations that enhance emotional processing, cognitive control, curiosity, and neuroendocrine regulation is examined in this review of squirrel monkey research.

Hayward C, Wilson KA. · Stanford University, CA 94305-5722, USA. · Behav Modif. · Pubmed #17307933 No free full text.

Abstract: This article reviews the controversy surrounding the diagnosis of agoraphobia without panic attacks and proposes a key role for anxiety sensitivity in explaining agoraphobic avoidance among those who have never experienced panic. Although rare in clinical samples, agoraphobia without panic is commonly observed in population-based surveys, including more recent studies in which misclassification bias is addressed. Differential treatment seeking may partially explain these discrepant findings; however, it remains unclear why agoraphobic avoidance develops in the absence of panic. Because anxiety sensitivity is a dispositional analogue of panic, it is proposed that high anxiety sensitivity is a risk factor for agoraphobic avoidance in the absence of frank panic attacks. Preliminary evidence to support this contention is reviewed.

Wollburg E, Kim S, Conrad A, Roth WT. · VA Palo Alto Health Care System, (116-PAD), 3801 Miranda Avenue, Palo Alto, CA 94304, USA. · Expert Rev Neurother. · Pubmed #17286547 No free full text.

Abstract: 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.

Schatz DB, Rostain AL. · Stanford University School of Medicine. · J Atten Disord. · Pubmed #17085624 No free full text.

Abstract: OBJECTIVE/METHOD: ADHD is often comorbid with anxiety disorders, with rates approaching 25% in many samples. This current review's goal is to examine the literature on ADHD with comorbid anxiety from 1998 to the present. RESULTS: Recent studies indicate that anxiety in ADHD may a) partially inhibit the impulsivity and response inhibition deficits, b) make working memory deficits worse, and c) may be qualitatively different from more phobic types of anxiety seen in pure anxiety samples. In examining subtypes of ADHD, measures of sluggish cognitive tempo show strong correlations with anxiety measures. Insights into the nature of the comorbidity between ADHD and anxiety may be gained by examining the possible comorbidity between Obsessive Compulsive Disorder and ADHD, shared risk factors for ADHD and anxiety, and the current pathogenic models of ADHD. CONCLUSION: The article concludes with a synthesis of the above work, along with directions for future research.

Conrad A, Roth WT. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. · J Anxiety Disord. · Pubmed #16949248 No free full text.

Abstract: 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.

Abad VC, Guilleminault C. · Stanford University Sleep Disorders Clinic and Sleep Research Center, Stanford, Calif, USA. · Dialogues Clin Neurosci. · Pubmed #16416705 No free full text.

Abstract: Psychiatric disorders constitute 15.4% of the disease burden in established market economies. Many psychiatric disorders are associated with sleep disturbances, and the relationship is often bidirectional. This paper reviews the prevalence of various psychiatric disorders, their clinical presentation, and their association with sleep disorders. Among the psychiatric disorders reviewed are affective disorders, psychosis, anxiety disorders (including posttraumatic stress disorder), substance abuse disorders, eating disorders, and attention deficit/hyperactivity disorders. The spectrum of associated sleep disorders includes insomnia, hypersomnia, nocturnal panic, sleep paralysis, hypnagogic hallucinations, restless legs/periodic limb movements of sleep, obstructive sleep apnea, and parasomnias. The effects on sleep of various psychotropic medications utilized to treat the above psychiatric disorders are summarized.

Glick ID, Horsfall JL. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5723, USA. · Clin Sports Med. · Pubmed #16169445 No free full text.

Abstract: Although enormous amounts of time and money have been invested in enhancing performance for college and professional athletes, their psychiatric needs have been minimally addressed. Given the virtual absence of controlled scientific literature, in this article the authors detail the diagnostic issues and delineate treatment principles, including: (1) making an accurate diagnosis; (2) setting realistic goals; (3) delivering psycho-education; (4) inducing the patient to undergo treatment, including involving the family and significant others; and (5) delivering appropriate treatment (the most difficult task). The objective is to improve performance and quality of life by treating the problem or psychiatric illness. A special concern is minimizing countertransference feelings and avoiding undertreatment, because by definition the athlete needs to perform.

Spiegel D. · Stanford University, Stanford, CA 94305-5718, USA. · J Trauma Dissociation. · Pubmed #16150672 No free full text.

Abstract: This paper calls for a broadening of the context within which we study responses to traumatic stress, the course of recovery, components of effective interventions, and assessments of outcome. Acute stress reactions to trauma as a spectrum include anxiety, dissociative, and depressive symptoms. The course of these symptoms may vary, with fluctuations between intrusion (positive) and avoidance/numbing/dissociative (negative) symptoms that may complicate assessment, treatment-seeking, and course of recovery. Components of effective treatments including affect management, cognitive restructuring, and social integration are discussed. Finally, a broader view of outcome assessment in such research is called for, including not just reduction in psychopathological symptoms but attention to coping styles, affect management, resilience, social reorganization, and sensitivity to subsequent trauma.

Roth WT. · Department of Veterans Affairs Health Care System, Palo Alto, CA 94304, USA. · Int J Psychophysiol. · Pubmed #16137780 No free full text.

Abstract: 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).

DiNucci EM. · Stanford University, Stanford, CA, USA. · Orthop Nurs. · Pubmed #16056170 No free full text.

Abstract: Complementary and alternative therapies continue to grow in popularity among healthcare consumers. Among those modalities is energy healing (EH) (Eisenberg et al., 1998). EH is an adjunctive treatment that is noninvasive and poses little downside risk to patients. Well more than 50 major hospitals and clinics throughout the United States offer EH to patients (DiNucci, research table on healthcare facilities that offer Reiki, unpublished data, 2002). The National Institutes of Health is funding numerous EH studies that are examining its effects on a variety of conditions, including temporomandibular joint disorders, wrist fractures, cardiovascular health, cancer, wound healing, neonatal stress, pain, fibromyalgia, and AIDS (National Institutes of Health, 2004a). Several well-designed studies to date show significant outcomes for such conditions as wound healing (Grad, 1965) and advanced AIDS (Sicher, Targ, Moore, & Smith, 1998), and positive results for pain and anxiety (Aetna IntelliHealth, 2003a; Wardell, Weymouth, 2004), among others (Gallob, 2003). It is also suggested that EH may have positive effects on various orthopaedic conditions, including fracture healing, arthritis, and muscle and connective tissue (Prestwood, 2003). Because negative outcomes risk is at or near zero throughout the literature, EH is a candidate for use on many medical conditions.

Ketter TA, Wang PW, Nowakowska C, Marsh WK. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California, USA. · Acta Psychiatr Scand Suppl. · Pubmed #15330935 No free full text.

Abstract: OBJECTIVE: To assess new treatment options for bipolar disorders. METHOD: Controlled studies of new treatments for bipolar disorders were identified by computerized searches and reviews of scientific meeting proceedings, and were compiled by drug category. RESULTS: Two main categories of medications, newer anticonvulsants and newer antipsychotics, are yielding emerging new treatment options for bipolar disorders. Newer anticonvulsants have diverse psychotropic profiles, and although not generally effective for acute mania, may have utility for other aspects of bipolar disorders (e.g. lamotrigine for maintenance or acute bipolar depression), or for comorbid conditions (e.g. gabapentin for anxiety or pain, topiramate for obesity, bulimia, alcohol dependence, or migraine, and zonisamide for obesity). In contrast, newer antipsychotics generally appear effective for acute mania, and some may ultimately prove effective in acute depression (e.g. olanzapine combined with fluoxetine, quetiapine) and maintenance (e.g. olanzapine). CONCLUSION: Emerging research is yielding new treatment options for bipolar disorders and comorbid conditions.

Barry JJ, Lembke A, Bullock KD. · Department of Psychiatry, Stanford University Medical Center, 401 Quarry Road MC 5723, Stanford, CA 94305, USA. · Clin EEG Neurosci. · Pubmed #15112459 No free full text.

Abstract: Interventions that have been utilized to control seizures in people with epilepsy have been employed by the psychiatric community to treat a variety of disorders. The purpose of this review will be to give an overview of the most prominent uses of antiepileptic drugs (AEDs) and devices like the Vagus Nerve Stimulator (VNS) and Transcranial Magnetic Stimulation (TMS) in the treatment of psychiatric disease states. By far, the most prevalent use of these interventions is in the treatment of mood disorders. AEDs have become a mainstay in the effective treatment of Bipolar Affective Disorder (BAD). The U.S. Food and Drug Administration has approved the use of valproic acid for acute mania, and lamotrigine for BAD maintenance therapy. AEDs are also effectively employed in the treatment of anxiety and aggressive disorders. Finally, VNS and TMS are emerging as possibly useful tools in the treatment of more refractory depressive illness.

Sheikh JI, Woodward SH, Leskin GA. · Veterans Affairs Palo Alto Healthcare System (116A-MP), Menlo Park, California 94025, USA. · Depress Anxiety. · Pubmed #14661188 No free full text.

Abstract: Disturbed sleep is a common clinical problem in anxiety disorders, particularly in patients with post-traumatic stress disorder (PTSD) and panic disorder (PD). Several studies have attempted to validate the subjective sleep complaints of these disorders using laboratory polysomnography. These attempts, typically focusing on PTSD or PD independently, have demonstrated inconsistent results. To our knowledge, no such studies have attempted to directly compare and contrast sleep disturbances in PTSD and PD together. Our review of the studies of subjective sleep disturbances, sleep architecture, and sleep-related biologic phenomena suggests that a comparative characterization of sleep disturbances in these two disorders is timely. Such an inference is based on our identification of several areas of convergence and divergence between PTSD and PD found in the published literature, as well as our own preliminary investigations. Specifically, PTSD and PD seem to converge on several sleep-related parameters, namely, sleep quality, presence of episodic parasomnias, and movement time. They also appear to diverge in other important sleep-related areas such as respiratory disturbances and the particular phenomenological nature of episodic parasomnias, namely nightmares or nocturnal panic attacks. Investigations focusing on such overlapping phenomena may provide groundwork for further elucidation of central fear systems underlying these two disorders. Additionally, such sleep studies have the potential to provide important insights into ongoing efforts to develop a cohesive conceptual framework into the patho-physiologies of these disorders.

Bullock K, Koran L. · Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, Stanford, California 94304, USA. · Drugs Today (Barc). · Pubmed #14586484 No free full text.

Abstract: No standard treatment exists for the DSM-IV Impulse Control Disorders, Not Elsewhere Classified, including Compulsive Buying Disorder. This paper reviews the suggested pharmacotherapies for this disorder and their theoretical basis. McElroy et al. first reported benefit from antidepressant therapy in three cases of Compulsive Buying Disorder with comorbid depression and anxiety. In a retrospective chart review, McElroy's group reported on 20 patients that benefited from antidepressants, often in combination with mood stabilizers. Lejoyeux reported on two patients in whom treatment of a comorbid mood disorder led to remission of compulsive buying behavior. Black reported fluvoxamine to be effective in patients without comorbid major depression, suggesting that improvement was independent of the treatment of mood symptoms. Kim reported improvement with naltrexone, an opioid antagonist, in a case series. Two double-blind placebo-controlled trials found fluvoxamine no better than placebo; however, in both studies patients kept shopping logs, which may have confounded the results. An open-label trial of citalopram and a double-blind crossover trial which excluded shopping logs both reported positive results. Twelve-month follow-up data for the open-label group found that remission rates at quarterly time points were independent of continuing drug therapy. The data reviewed above suggest that pharmacologic interventions may be effective for compulsive buying disorder. Whether pharmacological treatment is superior to placebo and whether it is more, less or equally effective compared to psychotherapeutic interventions remains to be established.

Meuret AE, Wilhelm FH, Ritz T, Roth WT. · University of Hamburg, Stanford University, and Department of Veterans Affairs Health Care System, USA. · Behav Modif. · Pubmed #14531164 No free full text.

Abstract: 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.

Wilhelm FH, Roth WT, Sackner MA. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, USA. · Behav Modif. · Pubmed #14531161 No free full text.

Abstract: 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.

Solvason HB, Ernst H, Roth W. · Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305-5723, USA. · Psychiatr Clin North Am. · Pubmed #12778841 No free full text.

Abstract: 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.

Steiner H, Carrion V, Plattner B, Koopman C. · Division of Child Psychiatry and Child Development, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305-5719, USA. · Child Adolesc Psychiatr Clin N Am. · Pubmed #12725010 No free full text.

Abstract: This article explores the complex relationship between dissociation and psychiatric trauma. Dissociation is described as a defense reaction, a risk factor for the development of posttraumatic stress disorder, and as a set of syndromal disturbances. The authors discuss various models proposed for the relationship between these. They outline developmental considerations in diagnosis and treatment and end by discussing further needed research.

Roth WT, Gomolla A, Meuret AE, Alpers GW, Handke EM, Wilhelm FH. · Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California, USA. · Depress Anxiety. · Pubmed #12219335 No free full text.

Abstract: 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.