Incremental Validity of Cognitive-Behavioral Therapy and Acceptance and Commitment Therapy Mechanisms for Anxiety and Panic Symptomology.

Background: acceptance and commitment therapy (ACT) and cognitive-behavioral therapy (CBT) are empirically supported treatments for anxiety and panic disorder (PD), though they differ in their putative vulnerability and maintenance processes. The present study examined the incremental validity of several of these models' proposed core processes, including anxiety sensitivity (AS), dispositional avoidance, experiential avoidance (EA), cognitive fusion (CF), and mindfulness, as well as the interaction of the processes within each model, in the prediction of anxiety and panic symptomology. Methods: a sample of US adults (n = 316) completed self-report measures of AS, dispositional avoidance, EA, CF, mindfulness, anxiety, and PD symptoms. A series of hierarchical multiple regression analyses were conducted. Results: hierarchical regression analyses indicated that AS, dispositional avoidance, and EA predicted anxiety and panic symptoms even after controlling for one another, CF, mindfulness, and demographic variables. Although mindfulness and CF was correlated with anxiety and panic at the univariate level, they did not predict either outcome above and beyond AS, dispositional avoidance, and EA. When interaction terms were added to the models, the interaction between AS and -dispositional avoidance was a significant predictor of panic and anxiety symptoms, whereas the interaction between EA and CF only predicted panic symptoms. None of the interactions that included mindfulness were significant predictors. Conclusions: these findings provide support the independent and interactive predictive value of traditional CBT (AS, dispositional avoidance, and AS-dispositional avoidance) and ACT (EA) processes for anxiety and panic symptoms, but raise questions about the incremental predictive utility of CF and mindfulness.

Lower serum selenium concentration associated with anxiety in children.

PURPOSE: Few studies have examined the role of selenium in anxiety. This study aimed to evaluate the association between serum selenium concentrations and anxiety disorders and symptoms in children. DESIGN AND METHODS: This study utilized data from 831 children participating in the China Jintan Child Cohort Study (mean age = 12.67 years; 46.1% female). Serum selenium samples were collected and anxiety was assessed using the Chinese version of the Screen for Child Anxiety Related Disorders. Six types of anxiety scores were calculated, including total anxiety, panic/somatic, generalized anxiety, separation anxiety, social anxiety, and school phobia. RESULTS: Controlling for covariates, children with lower serum selenium concentrations were more likely to meet clinical cutoffs for total anxiety (OR = 0.992, p < 0.01), panic/somatic disorder (OR = 0.993, p < 0.05), generalized anxiety disorder (OR = 0.990, p < 0.05), social anxiety disorder (OR = 0.991, p < 0.01), and school phobia (OR = 0.989, p < 0.01), but not separation anxiety (OR = 1.000, p > 0.05). Controlling for covariates, lower serum selenium concentrations were also associated with higher continuous total anxiety, generalized anxiety, and school phobia scores (p < 0.05). CONCLUSIONS: Lower serum selenium concentrations were associated with higher anxiety. To our knowledge, this was the first study to examine the relationship between serum selenium and anxiety disorders in a sample of children. Results indicate an association between children's micronutrient levels and anxiety disorders. PRACTICE IMPLICATIONS: Improving child nutrition may be a promising strategy to help reduce childhood anxiety.

Identification and medical utilization of newly diagnosed panic disorder: A Nationwide case-control study.

OBJECTIVE: Ascertaining comorbid illnesses and patterns of medical utilization early in the course of psychiatric illness can help identify patients with panic disorder. We investigated how such cases were diagnosed and the comorbidities associated with newly diagnosed panic disorder in a nationwide database. METHODS: We enrolled a large representative cohort of the general population in Taiwan (N = 1000,000) and selected 9759 cases of panic disorder from January 1, 2000 to December 31, 2013. The distribution of the departments in which the cases were identified and the medical utilization 12 months before diagnosis were analyzed. Based on a nested case-control study, four controls were randomly selected for each case and matched for sex, age, and incidence year. Conditional logistic regression was used to explore the factors associated with newly-diagnosed panic disorder such as demographic factors, concomitant medications, and physical and psychiatric comorbidities. RESULTS: Most (58.5%) cases of panic disorder were diagnosed in the psychiatry department, whereas only 3.7% were identified in the emergency department. Before diagnosis, the patients frequently visited the departments of internal medicine, family practice, and Chinese herbal medicine. A multivariate analysis revealed a higher number of physical and psychiatric comorbidities before diagnosis in the cases compared with the controls, especially depressive disorder and other anxiety disorders. CONCLUSIONS: Individuals with certain comorbidities and patterns of medical utilization are more likely to be diagnosed with panic disorder. We suggest providing more training to general practitioners and emergency physicians for the early diagnosis of panic disorder.

Diagnostic Utility of Sodium Lactate Infusion and CO2-35% Inhalation for Panic Disorder.

Laboratory measures have played an integral role in diagnosing pathology; however, compared to traditional medicine, psychiatric medicine has lagged behind in using such measures. A growing body of literature has begun to examine the viability and development of different laboratory measures in order to diagnose psychopathologies. The present review examines the current state of development of both sodium lactate infusion and CO2-35% inhalation as potential ancillary measures to diagnose panic disorder (PD). A previously established 3-step approach to identifying laboratory-based diagnostic tests was applied to available literature assessing the ability of both sodium lactate infusion or CO2-35% inhalation to induce panic attacks in PD patients, healthy controls, and individuals with other psychiatric conditions. Results suggest that across the literature reviewed, individuals with PD were more likely to exhibit panic attacks following administration of sodium lactate or CO2-35% compared to control participants. The majority of the studies examined only compared individuals with PD to healthy controls, suggesting that these ancillary measures are underdeveloped. In order to further determine the utility of these ancillary measures, research is needed to determine if panic attacks following administration of these chemical agents are unique to PD, or if individuals with related pathologies also respond, which may be indicative of transdiagnostic characteristics found across disorders.

Investigating effective treatment factors in brief cognitive behavioral therapy for panic disorder.

Numerous studies have provided evidence for the effectiveness of cognitive behavioral therapy (CBT) on panic disorders (PDs). There has also been growing attention on brief CBT with regard to delivering intensive treatment efficiently. This study investigated the essential parts of mindfulness-based brief CBT to optimize treatment benefits.A total of 37 patients were retrospectively enrolled in this study. They were recruited from the anxiety/panic/fear clinic of Seoul National University Hospital. The patients participated in group CBT once a week for a total of 4 sessions over a 4-week period, when they were assessed using the Panic Disorder Severity Scale (PDSS), Anxiety Sensitivity Index-Revised (ASI-R), Albany Panic and Phobia Questionnaire (APPQ), State-Trait Anxiety Inventory (STAI), Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and after brief CBT. Twenty-nine patients completed the 1-month follow-up.There were significant reductions in PDSS (P < .001), ASI-R-fear of respiratory symptoms (P = .006), ASI-R-fear of publicly observable anxiety reaction (P = .002), ASI-R-fear of cardiovascular symptoms (P < .001), ASI-R-fear of cognitive dyscontrol (P = .001), ASI-R-Total (P < .001), APPQ-Agoraphobia (P = .003), APPQ-Total (P = .028), STAI-State anxiety (P < .001), STAI-Trait anxiety (P = .002), BAI (P = .003), and BDI (P < .001) scores. We also found significant associations between ASI-R-fear of cardiovascular symptoms, ASI-R-Total, and changes in PDSS scores. A stepwise multiple linear regression analysis indicated that anxiety sensitivity for fear of cardiovascular symptoms predicted an improvement in panic severity (ß = 0.513, P = .004).Our findings suggested that behavioral aspects, especially physiological symptom control, needed to be considered in brief, intensive CBT for PD. The results also suggested that a mindfulness-based brief CBT approach might be particularly helpful for patients with PD who have severe cardiovascular symptoms.

Cultural aspects of anxiety disorders in India.

Cultural factors have influenced the presentation, diagnoses, and treatment of anxiety disorders in India for several centuries. This review covers the antecedents, prevalence, phenomenology, and treatment modalities of anxiety disorders in the Indian cultural context. It covers the history of the depiction of anxiety in India and the concept of culture in the classification of anxiety disorders, and examines the cultural factors influencing anxiety disorders in India. We review the prevalence and phenomenology of various disorders, such as generalized anxiety disorder, panic disorder, social anxiety, and phobic disorder, as well as culture-specific syndromes such as dhat and koro in India. Finally, the review examines the wide range of therapeutic modalities practiced in India, such as faith healing, psychotherapy, ayurveda, psychopharmacology, Unani medicine, homeopathy, yoga, meditation, and mindfulness. We conclude by emphasizing the significance of cultural factors in making relevant diagnoses and offering effective and holistic treatments to individuals with anxiety disorders.

Por varios siglos, Ios factores culturales han influenciado la presentación, diagnóstico y tratamiento de Ios trastornos de ansiedad. Esta revisión abarca Ios antecedentes, prevalencia, fenomenología y modalidades terapéuticas de Ios trastornos de ansiedad en el contexto cultural de India. También incluye la historia de la descripción de la ansiedad en India y el concepto de cultura en la clasificación de Ios trastornos de ansiedad, como asimismo examina Ios factores culturales que influyen en Ios trastornos de ansiedad en India. Se revisa la prevalencia y la fenomenología de varios trastornos, como el trastorno de ansiedad generalizada, el trastorno de pánico, la ansiedad social y el trastorno fóbico, como también síndromes culturales específicos en India como el dhat y el koro. Por ultimo, el artículo revisa el amplio rango de modalidades terapéuticas practicadas en India, como la curación por la fe, la psicoterapia, el ayurveda y la psicofarmacología. Se concluye enfatizando en el significado de Ios factores culturales que son relevantes para realizar diagnósticos y ofrecer tratamientos efectivos y holísticos para individuos con trastornos de ansiedad.

Depuis plusieurs siècles, des facteurs culturels influent sur la présentation, le diagnostic et le traitement des troubles anxieux en Inde. Cet article parcourt les antécédents, la prévalence, la phénoménologie et les modalités de traitement des troubles anxieux dans le contexte culturel indien. Il traite de l'histoire de la représentation de l'anxiété en Inde et du concept de culture dans la classification des troubles anxieux et analyse les facteurs culturels influant sur les troubles anxieux en Inde. Nous examinons la prévalence et la phénoménologie des différents troubles, comme les troubles anxieux généralisés, le trouble panique, l'anxiété sociale et les troubles phobiques, ainsi que les syndromes culturels spécifiques comme le syndrome du Dhat et du koro en Inde. Enfin, l'article analyse la large gamme de modalités thérapeutiques pratiquées en Inde, comme la guérison par la foi, la psychothérapie, l'ayurvéda, la psychopharmacologie, la médecine Unani, l'homéopathie, le yoga, la méditation et la pleine conscience. Nous concluons en soulignant l'importance des facteurs culturels dans l'établissement de diagnostics pertinents et en proposant des traitements efficaces et holistiques aux individus ayant des troubles anxieux.

Non-cardiac Chest Pain: A Review for the Consultation-Liaison Psychiatrist.

BACKGROUND: Patients presenting with chest pain to general practice or emergency providers represent a unique challenge, as the differential is broad and varies widely in acuity. Importantly, most cases of chest pain in both acute and general practice settings are ultimately found to be non-cardiac in origin, and a substantial proportion of patients experiencing non-cardiac chest pain (NCCP) suffer significant disability. In light of emerging evidence that mental health providers can serve a key role in the care of patients with NCCP, knowledge of the differential diagnosis, psychiatric co-morbidities, and therapeutic techniques for NCCP would be of great use to both consultation-liaison (C-L) psychiatrists and other mental health providers. METHODS: We reviewed prior published work on (1) the appropriate medical workup of the acute presentation of chest pain, (2) the relevant medical and psychiatric differential diagnosis for chest pain determined to be non-cardiac in origin, (3) the management of related conditions in psychosomatic medicine, and (4) management strategies for patients with NCCP. RESULTS: We identified key differential diagnostic and therapeutic considerations for psychosomatic medicine providers in 3 different clinical contexts: acute care in the emergency department, inpatient C-L psychiatry, and outpatient C-L psychiatry. We also identified several gaps in the literature surrounding the short-term and long-term management of NCCP in patients with psychiatric etiologies or co-morbid psychiatric conditions. CONCLUSIONS: Though some approaches to the care of patients with NCCP have been developed, more work is needed to determine the most effective management techniques for this unique and high-morbidity population.

Are there subtypes of panic disorder? An interpersonal perspective.

OBJECTIVE: Panic disorder (PD) is associated with significant personal, social, and economic costs. However, little is known about specific interpersonal dysfunctions that characterize the PD population. The current study systematically examined these interpersonal dysfunctions. METHOD: The present analyses included 194 patients with PD out of a sample of 201 who were randomized to cognitive-behavioral therapy, panic-focused psychodynamic psychotherapy, or applied relaxation training. Interpersonal dysfunction was measured with the Inventory of Interpersonal Problems-Circumplex (Horowitz, Alden, Wiggins, & Pincus, 2000). RESULTS: Individuals with PD reported greater levels of interpersonal distress than that of a normative cohort (especially when PD was accompanied by agoraphobia), but lower than that of a cohort of patients with major depression. There was no single interpersonal profile that characterized PD patients. Symptom-based clusters (with vs. without agoraphobia) could not be discriminated on core or central interpersonal problems. Rather, as revealed by cluster analysis based on the pathoplasticity framework, there were 2 empirically derived interpersonal clusters among PD patients that were not accounted for by symptom severity and were opposite in nature: domineering-intrusive and nonassertive. The empirically derived interpersonal clusters appear to be of clinical utility in predicting alliance development throughout treatment: Although the domineering-intrusive cluster did not show any changes in the alliance throughout treatment, the nonassertive cluster showed a process of significant strengthening of the alliance. CONCLUSIONS: Empirically derived interpersonal clusters in PD provide clinically useful and nonredundant information about individuals with PD.

Efficacy of treatments for anxiety disorders: a meta-analysis.

To our knowledge, no previous meta-analysis has attempted to compare the efficacy of pharmacological, psychological and combined treatments for the three main anxiety disorders (panic disorder, generalized anxiety disorder and social phobia). Pre-post and treated versus control effect sizes (ES) were calculated for all evaluable randomized-controlled studies (n = 234), involving 37,333 patients. Medications were associated with a significantly higher average pre-post ES [Cohen's d = 2.02 (1.90-2.15); 28,051 patients] than psychotherapies [1.22 (1.14-1.30); 6992 patients; P < 0.0001]. ES were 2.25 for serotonin-noradrenaline reuptake inhibitors (n = 23 study arms), 2.15 for benzodiazepines (n = 42), 2.09 for selective serotonin reuptake inhibitors (n = 62) and 1.83 for tricyclic antidepressants (n = 15). ES for psychotherapies were mindfulness therapies, 1.56 (n = 4); relaxation, 1.36 (n = 17); individual cognitive behavioural/exposure therapy (CBT), 1.30 (n = 93); group CBT, 1.22 (n = 18); psychodynamic therapy 1.17 (n = 5); therapies without face-to-face contact (e.g. Internet therapies), 1.11 (n = 34); eye movement desensitization reprocessing, 1.03 (n = 3); and interpersonal therapy 0.78 (n = 4). The ES was 2.12 (n = 16) for CBT/drug combinations. Exercise had an ES of 1.23 (n = 3). For control groups, ES were 1.29 for placebo pills (n = 111), 0.83 for psychological placebos (n = 16) and 0.20 for waitlists (n = 50). In direct comparisons with control groups, all investigated drugs, except for citalopram, opipramol and moclobemide, were significantly more effective than placebo. Individual CBT was more effective than waiting list, psychological placebo and pill placebo. When looking at the average pre-post ES, medications were more effective than psychotherapies. Pre-post ES for psychotherapies did not differ from pill placebos; this finding cannot be explained by heterogeneity, publication bias or allegiance effects. However, the decision on whether to choose psychotherapy, medications or a combination of the two should be left to the patient as drugs may have side effects, interactions and contraindications.

Diagnosis and management of generalized anxiety disorder and panic disorder in adults.

Generalized anxiety disorder (GAD) and panic disorder (PD) are among the most common mental disorders in the United States, and they can negatively impact a patient's quality of life and disrupt important activities of daily living. Evidence suggests that the rates of missed diagnoses and misdiagnosis of GAD and PD are high, with symptoms often ascribed to physical causes. Diagnosing GAD and PD requires a broad differential and caution to identify confounding variables and comorbid conditions. Screening and monitoring tools can be used to help make the diagnosis and monitor response to therapy. The GAD-7 and the Severity Measure for Panic Disorder are free diagnostic tools. Successful outcomes may require a combination of treatment modalities tailored to the individual patient. Treatment often includes medications such as selective serotonin reuptake inhibitors and/or psychotherapy, both of which are highly effective. Among psychotherapeutic treatments, cognitive behavior therapy has been studied widely and has an extensive evidence base. Benzodiazepines are effective in reducing anxiety symptoms, but their use is limited by risk of abuse and adverse effect profiles. Physical activity can reduce symptoms of GAD and PD. A number of complementary and alternative treatments are often used; however, evidence is limited for most. Several common botanicals and supplements can potentiate serotonin syndrome when used in combination with antidepressants. Medication should be continued for 12 months before tapering to prevent relapse.

Hypnosis aided fixed role therapy for social phobia: a case report.

This case study details how hypnosis aided fixed role therapy (HAFRT) was employed in the successful treatment of a case of social phobia with a history of refractory outcomes to previous therapy trials. The treatment consisted of 10 office sessions, scheduled every two weeks, of HAFRT along with twice a day self-hypnotic sessions where the patient performed multiple visualization rehearsals of the vignettes that were successfully mastered in hypnosis during office visits. The results indicated that this patient was able to engage in social and professional affairs that were impossible prior to treatment. The patient retained the therapy gains at follow up 6 months later.

Mindfulness-based stress reduction for comorbid anxiety and depression: case report and clinical considerations.

Growing research literature has documented the effectiveness of mindfulness-based interventions for anxiety and depressive disorders. Mindfulness-based stress reduction (MBSR) teaches a series of mindfulness meditation and yoga practices, delivered in a group format during eight weekly sessions plus one full-day session. This case report demonstrates how MBSR was associated with dramatic clinical improvement of an individual with symptoms of panic, generalized anxiety, and depression. Scores on clinical assessment measures suggested clinically severe levels of anxious arousal, generalized anxiety, worry, fear of negative evaluation, and depression at the beginning of the intervention. The scores on all these measures fell well within normal limits 7 weeks later at the end of the intervention, and no remaining symptoms were reported afterward. Increased life satisfaction and quality of life were documented as well. This case illustrates the potential benefit of MBSR as an alternative or adjunctive treatment for comorbid anxiety and depressive disorder symptoms.

Transtornos de ansiedade: terapia com estimulação magnética transcraniana / Anxiety disorders: treatment with transcranial magnetic stimulation

Dentre os transtornos psiquiátricos, os transtornos de ansiedade (TAs) são os mais comuns, com prevalência em torno de 20% na população e, portanto, provocam grande prejuízo a pacientes e familiares. São vários os subtipos de transtornos de ansiedade e um diagnóstico correto se baseia em uma avaliação clínica cuidadosa. No presente artigo apresentamos os diagnósticos e os achados mais recentes sobre o tratamento com estimulação magnética transcraniana repetitiva (EMTr) para o transtorno de pânico, transtorno obsessivo-compulsivo, transtorno de estresse pós-traumático e fobia social.

Among psychiatric disorders, anxiety disorders (ATs) are the most common, with a prevalence of around 20% in the population and with great harm to patients and families. There are several subtypes of anxiety disorders and a correct diagnosis is based on a careful clinical assessment. In this paper we present the findings and the latest findings about treatment with repetitive transcranial magnetic stimulation (rTMS) for panic disorder, obsessive-compulsive disorder, post-traumatic stress and social phobia.

Opposing breathing therapies for panic disorder: a randomized controlled trial of lowering vs raising end-tidal P(CO2).

BACKGROUND: Teaching anxious clients to stop hyperventilating is a popular therapeutic intervention for panic. However, evidence for the theory behind this approach is tenuous, and this theory is contradicted by an opposing theory of panic, the false-suffocation alarm theory, which can be interpreted to imply that the opposite would be helpful. OBJECTIVE: To test these opposing approaches by investigating whether either, both, or neither of the 2 breathing therapies is effective in treating patients with panic disorder. METHOD: We randomly assigned 74 consecutive patients with DSM-IV-diagnosed panic disorder (mean age at onset = 33.0 years) to 1 of 3 groups in the setting of an academic research clinic. One group was trained to raise its end-tidal P(CO2) (partial pressure of carbon dioxide, mm Hg) to counteract hyperventilation by using feedback from a hand-held capnometer, a second group was trained to lower its end-tidal P(CO2) in the same way, and a third group received 1 of these treatments after a delay (wait-list). We assessed patients physiologically and psychologically before treatment began and at 1 and 6 months after treatment. The study was conducted from September 2005 through November 2009. RESULTS: Using the Panic Disorder Severity Scale as a primary outcome measure, we found that both breathing training methods effectively reduced the severity of panic disorder 1 month after treatment and that treatment effects were maintained at 6-month follow-up (effect sizes at 1-month follow-up were 1.34 for the raise-CO(2) group and 1.53 for the lower-CO(2) group; P < .01). Physiologic measurements of respiration at follow-up showed that patients had learned to alter their P(CO2) levels and respiration rates as they had been taught in therapy. CONCLUSIONS: Clinical improvement must have depended on elements common to both breathing therapies rather than on the effect of the therapies themselves on CO(2) levels. These elements may have been changed beliefs and expectancies, exposure to ominous bodily sensations, and attention to regular and slow breathing. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00183521.

Disorder-specific emotional imagery for differential and quantitative assessment of agoraphobia.

Visual emotional stimulation is supposed to elicit psycho-vegetative reactions, which are similar to as the ones elicited by exposure to actual experience. Visual stimulation paradigms have been widely used in studies on agoraphobia with and without panic disorder. However, the applied imagery has hardly ever been disorder- and subject- specific. 51 patients with an ICD-10 and DSM-IV diagnosis of agoraphobia with or without panic disorder (PDA) and matching healthy controls have been examined. Subjects were confronted with 146 picture showing characteristic agoraphobic situations (high places, narrow places, crowds, public transport facilities, or wide places) or pictures associated with acute physical emergency (panic) situations, which had been pre-selected by anxiety experts. Participants were asked to rate emotional arousal induced by the respective images on the Self- Assessment Manikin scale (SAM). Data on PDA severity (PAS) depressive symptoms (MADRS) and sociodemographic data were recorded. Saliva cortisol levels were measured before and after exposure in a second test applying the individually mostly feared stimuli combined with emotionally neutral pictures for every single patient. 117 of the PDA-specific images were rated significantly more fear-eliciting by patients than by healthy individuals. Sub-categorization into agoraphobia clusters showed differential effects of clusters with regard to gender distribution, severity of PDA and cortisol secretion during exposure. In this study disorder specific and individual characteristics of agoraphobia were assessed for use in future trials applying emotional imagery. It could be used for the differential assessment of PDA and associated neurobiological and psychological phenomena and in neuroimaging paradigms.

Explanatory models of mental disorders and treatment practices among traditional healers in Mpumulanga, South Africa.

OBJECTIVE: In many traditional belief systems in Africa, including South Africa, mental health problems may be attributed to the influence of ancestors or to bewitchment. Traditional healers are viewed as having the expertise to address these causes. However, there is limited information on their explanatory models and consequent treatment practices. The present study examines traditional healers' explanatory models (EMs) and treatment practices for psychotic and non-psychotic mental illnesses. METHOD: 4 focus group discussions (8 healers in each group) and 18 in-depth interviews were conducted. Four vignettes were presented (schizophrenia, depression, panic and somatisation) and traditional healers' views on the nature of the problem, cause, consequence, treatment and patient expectations were elicited. RESULTS: Traditional healers held multiple explanatory models for psychotic and non-psychotic disorders. Psychotic illnesses appear to be the main exemplar of mental illness and were treated with traditional medicine, while nonpsychotic illnesses were not viewed as a mental illness at all. Additionally, traditional healers do not only use herbs and substances solely from "traditional" sources but rather have incorporated into their treatment practices modern ingredients that are potentially toxic. CONCLUSION: Interventions aimed at increasing the mental health literacy of traditional healers are essential. In addition, investigations of the effectiveness of traditional healer treatment for psychiatric disorders should be conducted.

Respiratory and cognitive mediators of treatment change in panic disorder: evidence for intervention specificity.

OBJECTIVE: There are numerous theories of panic disorder, each proposing a unique pathway of change leading to treatment success. However, little is known about whether improvements in proposed mediators are indeed associated with treatment outcomes and whether these mediators are specific to particular treatment modalities. Our purpose in this study was to analyze pathways of change in theoretically distinct interventions using longitudinal, moderated mediation analyses. METHOD: Forty-one patients with panic disorder and agoraphobia were randomly assigned to receive 4 weeks of training aimed at altering either respiration (capnometry-assisted respiratory training) or panic-related cognitions (cognitive training). Changes in respiration (PCO2, respiration rate), symptom appraisal, and a modality-nonspecific mediator (perceived control) were considered as possible mediators. RESULTS: The reductions in panic symptom severity and panic-related cognitions and the improvements in perceived control were significant and comparable in both treatment groups. Capnometry-assisted respiratory training, but not cognitive training, led to corrections from initially hypocapnic to normocapnic levels. Moderated mediation and temporal analyses suggested that in capnometry-assisted respiratory training, PCO2 unidirectionally mediated and preceded changes in symptom appraisal and perceived control and was unidirectionally associated with changes in panic symptom severity. In cognitive training, reductions in symptom appraisal were bidirectionally associated with perceived control and panic symptom severity. In addition, perceived control was bidirectionally related to panic symptom severity in both treatment conditions. CONCLUSION: The findings suggest that reductions in panic symptom severity can be achieved through different pathways, consistent with the underlying models.

Effect of gender on processing threat-related stimuli in patients with panic disorder: sex does matter.

BACKGROUND: Several studies have shown that female and male subjects process emotions differently. As women appear to be especially sensitive and responsive to negative and threatening stimuli, gender-specific emotional processing might be an important factor contributing to the increased likelihood of women compared to men to develop anxiety disorders, e.g. panic disorder (PD). METHODS: In this study, gender-specific neural activation during facial emotion processing was investigated in 20 PD patients (12 women, 8 men) by functional magnetic resonance imaging. RESULTS: Overall, significantly stronger activation, encompassing the amygdala, prefrontal, temporal, and occipital cortical areas, basal ganglia, and thalamus, was observed in women than in men during the processing of angry, fearful, or neutral but not happy facial expressions. Additionally, functional connectivity between the amygdala and prefrontal cortical areas and thalamus during the processing of angry facial expressions was significantly stronger in women than in men. CONCLUSIONS: These results emphasize gender as an important variable in neural activation patterns of emotional processing and may help to further elucidate the biological substrate of gender-specific susceptibility for PD.

A randomized, controlled trial of aerobic exercise in combination with paroxetine in the treatment of panic disorder.

OBJECTIVES: Regular aerobic exercise (running) has been shown to be superior to a pill placebo in the treatment of panic disorder. Combined drug and exercise treatment has not been investigated in randomized controlled studies to date. METHODS: This is a randomized, 10-week, controlled, parallel group, pilot study. A total of 75 outpatients with panic disorder with or without agoraphobia (DSM-IV and ICD-10) received either (1) exercise plus paroxetine 40 mg/day (n=21), (2) relaxation plus paroxetine (n=17), (3) exercise plus pill placebo (n=20), or (4) relaxation plus pill placebo (n=17). Changes in the Panic and Agoraphobia Scale (P&A), and the Clinical Global Impression Scale (CGI) underwent repeated measure analysis. RESULTS: Effects sizes were large for all groups (d=1.53-3.87), however not significantly different. Paroxetine-treated patients were significantly more improved than placebo-treated patients. On the CGI, patients in the exercise groups (plus paroxetine or placebo) had a trend toward better improvement compared to relaxation (P=0.06). Response and remission rates were higher in the paroxetine compared to pill placebo groups. CONCLUSIONS: While paroxetine was superior to placebo, aerobic exercise did not differ from relaxation training in most efficacy measures.

Altered auditory processing in patients with panic disorder: a pilot study.

OBJECTIVES: Clinical and electrophysiological studies suggest that panic disorder (PD) patients show disturbed response inhibition to sensory stimuli. Thus, habituation of neuronal activation after repeated sine tone stimulation was assessed by functional magnetic resonance imaging (fMRI) in patients with PD. METHODS: Twenty patients with PD and 20 age- and gender-matched healthy controls were assessed by 3T fMRI for auditory habituation. During three stimulation cycles of digitally generated pulsed (ν=5 Hz) 800-Hz sine tones alternating with silent periods, activation of the auditory cortex and other anxiety- or sensory integration-related regions was assessed. Brain activation was further analyzed dependent on functional serotonin transporter (5-HTT) gene variation (5-HTTLPR). RESULTS: PD patients demonstrated an extended brain activity in the first stimulation block, which normalized during the second stimulation cycle. A positive correlation with anxiety measures (HAMA) and an increased activity of distinct anxiety- or sensory integration-related areas (e.g., BA 22, BA 10) were seen during the third block of auditory stimulation. There was a significant interaction of left amygdala activation and the 5-HTTLPR S allele. CONCLUSIONS: Our results support the hypothesis of an aberrant processing of sensory information in PD patients. This phenomenon may underlie an enhanced responsiveness to anxiety-relevant or irrelevant stimuli possibly increasing PD vulnerability.