Heart rate variability: A biomarker of selective response to mindfulness-based treatment versus fluoxetine in generalized anxiety disorder.

BACKGROUND: Mindfulness-based interventions (MBIs) are effective for some, but not all patients with anxiety disorders, but no clinical features have been consistently able to differentiate which patients are more likely to respond. In this study, we tested heart rate variability (HRV), a proposed correlate of regulated emotional response, as a moderator of treatment response to an MBI compared with pharmacotherapy. METHODS: Seventy-seven patients with GAD had HRV data collected before randomization to pharmacological treatment with fluoxetine or Body-in-Mind Training (an MBI focused on bodily movement attention). HRV was used to predict treatment response measured by the Hamilton anxiety rating scale at 0 (baseline), 5, and 8 weeks (end of the intervention). RESULTS: The HF (nu) index of HRV was a strong moderator of treatment response between BMT and fluoxetine (estimate = 4.27 95%CI [1.19, 8.19]). Although fluoxetine was overall slightly superior to BMT in this study, no differences were found between groups in patients with high HF (nu) scores (estimate = -1.85 CI95% [-9.21, 5.52]). In contrast, patients with low HF (nu) achieved lower anxiety rating scores with fluoxetine treatment when compared with BMT (estimate = -10.29, 95% CI [-17.59, -2.99]). LIMITATIONS: A relatively small sample of patients was included. CONCLUSIONS: HRV was able to identify a subgroup for which MBI was less effective than pharmacotherapy and is a promising candidate as a selective biomarker for treatment response between an MBI and fluoxetine.

Neurostimulation in Anxiety Disorders, Post-traumatic Stress Disorder, and Obsessive-Compulsive Disorder.

Many pharmacological treatments were proved effective in the treatment of panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD); still many patients do not achieve remission with these treatments. Neurostimulation techniques have been studied as promising alternatives or augmentation treatments to pharmacological and psychological therapies. The most studied neurostimulation method for anxiety disorders, PTSD, and OCD was repetitive transcranial magnetic stimulation (rTMS). This neurostimulation technique had the highest level of evidence for GAD. There were also randomized sham-controlled trials indicating that rTMS may be effective in the treatment of PTSD and OCD, but there were conflicting findings regarding these two disorders. There is indication that rTMS may be effective in the treatment of panic disorder, but the level of evidence is low. Deep brain stimulation (DBS) was most studied for treatment of OCD, but the randomized sham-controlled trials had mixed findings. Preliminary findings indicate that DBS could be affective for PTSD. There is weak evidence indicating that electroconvulsive therapy, transcranial direct current stimulation, vagus nerve stimulation, and trigeminal nerve stimulation could be effective in the treatment of anxiety disorders, PTSD, and OCD. Regarding these disorders, there is no support in the current literature for the use of neurostimulation in clinical practice. Large high-quality studies are warranted.

Panic attack provocation in panic disorder patients with a computer simulation.

BACKGROUND: Computer simulations (CS) and virtual reality exposure are promising techniques for research and treatment of panic disorder with agoraphobia (PDA). The objective of this study was to ascertain whether a given CS was a stimulus capable of producing panic attacks (PAs), anxiety and psychophysiological changes in patients with PDA. METHODS: Thirty PDA patients and 30 healthy subjects were recruited for this study. Subjects were exposed to a 3-min CS of a situation relevant to agoraphobic patients. Anxiety, panic symptoms, PAs, heart rate, skin conductance and respiration were recorded before, during and after the CS exposure. RESULTS: The CS effectively induced anxiety, hyperventilation and electrodermal responses in PDA patients but not in healthy subjects. Forty percent of PDA patients had a PA while none of the control subjects had a PA. A subgroup of patients who were less sensitive to the CS than the other subgroup of PDA patients and did not present full-blown PAs still had more panic symptoms, higher anxiety levels and more respiratory irregularities than the controls. LIMITATIONS: Low immersion and low sense of presence, lack of interaction with the environment. CONCLUSIONS: Exposure to the CS produced effects similar to in vivo exposure, respiratory and caffeine challenges. Subsequent studies should: make direct comparisons between CS and other challenges for PDA; investigate if CS can be a tool for predicting effects of medication; determine the potential of CS as a desensitization technique for situational PAs.

Panic Disorder and Chronic Caffeine Use: A Case-control Study.

BACKGROUND: Acute administration of caffeine produces panic attacks in most Panic Disorder (PD) patients, but little is known about chronic caffeine use in these patients. OBJECTIVE: To assess caffeine use in patients with PD and to ascertain if caffeine consumption is associated with sociodemographic or clinical features. METHODS: 65 adults with PD and 66 healthy controls were included in the current study. Their caffeine intake within the previous week was quantified with a questionnaire and compared. Harmful caffeine use was defined as consumption above 400 mg/day of caffeine. We tested for correlations between caffeine intake, demographic and clinical features. RESULTS: Patients consumed significantly more caffeine than controls (P < 0.001). 14% (N = 9) of the PD patients made harmful use of caffeine. The use of caffeine-containing medications was observed in 40% (N = 26) of the PD patients and 6% (N = 4) of controls. Consumption of energy drinks was observed in 11% (N = 7) of PD patients and in none of the healthy subjects. Patients reported sleeping significantly less than controls (P < 0.001). In PD patients, caffeine consumption was not correlated with the presence of panic attacks or comorbidity with depression. The use of benzodiazepines or sedative medications was not correlated with caffeine intake. CONCLUSION: High caffeine consumption in PD patients could be explained by the development of tolerance with regular use of this substance. Subtypes of sensitive and non-sensitive PD patients could also explain why some of these patients are able to tolerate high doses of caffeine.

Quality of life in panic disorder: the influence of clinical features and personality traits / Qualidade de vida no transtorno de pânico: a influência de características clínicas e traços de personalidade

Abstract Objective To identify which clinical features and personality traits are associated with quality of life (QoL) in panic disorder (PD) patients. Methods This was a cross-sectional study with PD patients. The brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Big Five Inventory (BFI) were used to assess QoL and personality traits respectively. The strength of correlations was measured with Pearson's, Spearman's, and point-biserial correlation coefficients. We also performed multiple linear regressions, considering sociodemographic data and scores from clinical scales as independent variables and QoL scores as dependent variables. Results A total of 98 patients were evaluated. Depressive symptoms had a strong negative correlation with QoL and, to a lesser extent, panic and anxiety symptoms were also negatively correlated with QoL. While consciousness, extraversion, and agreeableness had mild positive correlations with QoL, neuroticism had a strong negative correlation. Conclusion Symptoms of depression, anxiety, and panic seem to have a negative impact on the QoL of PD patients. Personality traits, especially neuroticism, may also influence QoL in these patients.

Resumo Objetivo Identificar quais características clínicas e traços de personalidade são mais associados à qualidade de vida (QdV) em pacientes com transtorno de pânico (TP). Métodos Este foi um estudo transversal, realizado em pacientes com TP. A versão breve do Questionário de Qualidade de Vida da Associação Mundial de Saúde (World Health Organization Quality of Life Questionnaire - WHOQOL-BREF) e o Inventário dos Cinco Grande Fatores (Big Five Inventory - BFI) foram utilizados para avaliar QdV e traços de personalidade, respectivamente. A força de associação foi medida através da correlação de Pearson, de Spearman ou ponto bisserial. Foram também realizadas regressões lineares múltiplas, considerando os dados sociodemográficos e escores obtidos nas escalas clínicas como variáveis independentes, e os escores de QdV como variáveis dependentes. Resultados Um total de 98 pacientes foram avaliados. Sintomas depressivos apresentaram uma forte relação negativa com QdV; em menor intensidade, sintomas de TP e ansiosos também se correlacionaram com QdV. Nos domínios de personalidade, enquanto conscienciosidade, extroversão e amabilidade apresentaram uma leve correlação positiva com QdV, neuroticismo apresentou forte correlação negativa. Conclusão Sintomas depressivos, ansiosos e de TP parecem ter forte impacto negativo na QdV dos pacientes com TP. Traços de personalidade, principalmente neuroticismo, podem influenciar QdV nesses pacientes.

Neuroimaging findings as predictors of treatment outcome of psychotherapy in anxiety disorders.

Anxiety disorders are the largest group of mental disorders and a leading cause of impairment, implicating in high costs for health systems and society. Effective pharmacological and psychological treatments are available, but a significant fraction of these patients does not respond adequately to these treatments. The objective of this study is to identify neuroimaging findings that could predict response to psychotherapy in anxiety disorders. METHODS: The authors reviewed psychotherapy clinical trials with neuroimaging conducted with patients with anxiety disorders. A systematic review was performed in MEDLINE database through PubMed, the Cochrane Collaboration's Clinical Trials Register (CENTRAL), PsycINFO and Thomson Reuters's Web of Science. RESULTS: From the studies included in this review, 24 investigated anxiety disorder patients, and findings in the amygdala, dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC) and insula predicted response to psychotherapy in social anxiety disorder. Findings in ACC, hippocampus, insula, dlPFC, amygdala and inferior frontal gyrus (iFG) predicted response to psychotherapy in panic disorder and generalized anxiety disorder. LIMITATIONS: There was great heterogeneity between the included studies regarding neuroimaging techniques and the tasks performed during functional neuroimaging. CONCLUSION: Neuroimaging studies suggest that abnormalities in hippocampus, amygdala, iFG, uncus and areas linked with emotional regulation (dlPFC and ACC), predict a good outcome to psychotherapy in anxiety disorders.

Quality of life in panic disorder: the influence of clinical features and personality traits.

OBJECTIVE: To identify which clinical features and personality traits are associated with quality of life (QoL) in panic disorder (PD) patients. METHODS: This was a cross-sectional study with PD patients. The brief version of the World Health Organization Quality of Life Questionnaire (WHOQOL-BREF) and the Big Five Inventory (BFI) were used to assess QoL and personality traits respectively. The strength of correlations was measured with Pearson's, Spearman's, and point-biserial correlation coefficients. We also performed multiple linear regressions, considering sociodemographic data and scores from clinical scales as independent variables and QoL scores as dependent variables. RESULTS: A total of 98 patients were evaluated. Depressive symptoms had a strong negative correlation with QoL and, to a lesser extent, panic and anxiety symptoms were also negatively correlated with QoL. While consciousness, extraversion, and agreeableness had mild positive correlations with QoL, neuroticism had a strong negative correlation. CONCLUSION: Symptoms of depression, anxiety, and panic seem to have a negative impact on the QoL of PD patients. Personality traits, especially neuroticism, may also influence QoL in these patients.

Negative Affect Mediates Impulsivity in Generalized Anxiety Disorder.

INTRODUCTION: Although anxiety and impulsivity are intuitively thought to be inversely correlated, increased impulsivity has been associated both with generalized anxiety disorder (GAD) diagnosis and GAD symptoms in non-clinical samples. The emotional dysregulation model of GAD posits that patients experience more frequent and intense negative emotions while having poor regulatory control over emotional states and greater negative reactivity to their emotions. We hypothesized that poor regulatory control in the presence of negative emotions might explain the increased impulsivity found in GAD patients. In this study, we examined if negative affect mediates the relationship between GAD and impulsivity. METHODS: Thirty-four GAD patients and 35 healthy controls were included, and evaluated with measurements of impulsivity, negative and positive emotions, the severity of worrying and GAD symptoms, depression, and 5-factor personality traits. RESULTS: Global impulsivity scores and the attentional facet of impulsivity were higher in the patient group when compared to the controls. Negative affect was correlated with global impulsivity in the patient group only and explained impulsivity in our regression model while worrying and depressive symptoms did not. An indirect relationship was found between diagnosis and impulsivity through negative affect. CONCLUSION: Our study showed that the cardinal symptom of GAD - worrying - was not independently related to impulsivity in our sample. Increased impulsivity in GAD seems to be mediated by the increased presence of negative emotions, as it is common in mood and impulse-control disorders, indicating an unspecific shared vulnerability factor to psychopathology.

The impact of fibromyalgia syndrome and the role of comorbidity with mood and post-traumatic stress disorder in worsening the quality of life.

BACKGROUND:: The aim is to measure the association between fibromyalgia syndrome (FMS) and post-traumatic stress disorder (PTSD), mood and anxiety disorders using reliable psychiatric diagnoses according to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) and with a case-control design. METHODS:: Case-control study with cases (71 consecutive female patients with FMS) and controls (284 subjects without FMS), randomly drawn after a gender- and age-matching technique from the database of an epidemiological survey. Psychiatric diagnoses were conducted according to DSM-IV and carried out by clinical staff using a structured interview (Advanced Neuropsychiatric Tools and Assessment Schedule). QoL was measured by Short Form Health Survey (SF-12). RESULTS:: The lifetime prevalence of major depressive disorder (MDD; 43.7% vs 8.1%, p < .0001), bipolar disorder (BD; 21.1% vs 0.7%, p < .0001), PTSD (8.4% vs 1.4%, p < .0001) and panic disorder (28.2% vs 5.6%, p < .001) was higher in people with FMS than in controls. People with FMS showed a poorer QoL than controls on the SF-12 (26.43 ± 6.04 vs 37.45 ± 5.80, p < .0001). Those with comorbidity with MDD and BD showed a mean SF-12 score of 24.75 ± 6.31 versus 29.52 ± 4.84 ( N = 25) of people with FMS without any mood disorder ( p = .002). The attributable burden of FMS in worsening QoL was found comparable to that of serious chronic diseases such as multiple sclerosis. CONCLUSION:: FMS is a disorder that 'in itself' can have a devastating impact on an individual's life. The frequency of the association with major depressive and bipolar disorders increases the impact on the QoL of people with FMS. One of the causes of this association appears to be the extreme vulnerability to chronic stress that this disorder involves. The findings have important clinical significance: the physician must interpret in the right dimension and with dignity the suffering of the people with FMS.

Tranylcypromine Plus Amitriptyline for Electroconvulsive Therapy-Resistant Depression: A Long-Term Study.

BACKGROUND: Few therapeutic options are available for patients with electroconvulsive therapy-resistant major depressive disorder (ECT-r MDD), leaving a substantial proportion of this population beyond treatment possibilities. The combination of monoamine oxidase inhibitors and tricyclic antidepressants could be a potential strategy for managing ECT-r MDD, and the specific association of amitriptyline and tranylcypromine may offer additional tolerability advantages. Although promising, in our knowledge, no studies have examined until now the effectiveness of this combination in ECT-r MDD. METHODS: We report a retrospective cohort of 31 patients with ECT-r MDD treated in an open-label fashion with the combination of amitriptyline and tranylcypromine. RESULTS: Overall, 80.6% of the sample met response criteria at the end of the first 12 weeks of treatment. Seventy-six percent (19 of 25) of the responders were followed for a mean of 9.37 ± 3.86 years. During this follow-up period, none of the patients had a recurring depressive episode. The combination was well tolerated, whereas minor adverse effects were common, and no severe or life-threatening events were reported throughout the study. CONCLUSIONS: These findings indicate that the combination tranylcypromine and amitriptyline is a potentially safe and effective candidate for future investigation in the treatment and long-term maintenance of ECT-r MDD.

Personality Traits in Panic Disorder Patients With and Without Comorbidities.

Panic disorder (PD) is often correlated with high neuroticism and low extraversion. This study aims to ascertain whether PD patients differ from healthy controls in regard to personality traits and determine if these traits are correlated with comorbid disorders, anxiety, and depression symptoms. Personality traits of 69 PD patients and 42 controls were compared using the Maudsley Personality Inventory. In PD patients, comorbidities, anxiety, and depression symptoms were also evaluated. PD patients showed higher neuroticism and lower extraversion compared with healthy controls. Patients without comorbidities presented similar results to controls, whereas those with comorbidities presented higher neuroticism and lower extraversion scores. PD per se may be unrelated to deviant personality traits, although comorbidities with major depressive disorder and agoraphobia are probably associated with high neuroticism and low extraversion. These traits show a strong correlation with the accumulation and severity of these disorders.

Can Long-Term Pharmacotherapy Prevent Relapses in Generalized Anxiety Disorder? A Systematic Review.

BACKGROUND AND OBJECTIVES: Generalized anxiety disorder (GAD) is a persistent anxiety disorder with a high rate of relapse. While several trials have demonstrated the efficacy of pharmacotherapy for GAD treatment, fewer studies have investigated its efficacy in preventing symptom relapse in long-term treatment. The aim of this study is to evaluate if long-term pharmacotherapy may prevent relapses in GAD patients. METHODS: This is a systematic review of the relapse prevention trials with GAD patients. RESULTS: Eight trials were included in this review with 5304 patients in total. All patients showed a higher risk of relapse if treatment was not maintained for at least 6 months after remission, with hazard ratios ranging from 0.12 to 0.58 and mostly moderate effect sizes (0.19-1.06). CONCLUSION: Long-term pharmacotherapy may prevent symptom relapse in GAD patients. As the relapse rate is very high, the data support the continuation of pharmacotherapy for as long as possible.

A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis.

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but its neurobiological basis has been poorly studied. A few cognitive models have been proposed for understanding GAD development and maintenance. The aim of this study is to review functional Magnetic Resonance Image (fMRI) studies conducted with GAD patients and evaluate if they support and underpin the theoretical cognitive models proposed for this anxiety disorder. METHODS: A literature systematic review was undertaken in PubMed and ISI databases with no time limits. RESULTS: From the studies included in this review, 10 explored the "emotional dysregulation model", showing, prefrontal cortex (PFC) and anterior cingulate cortex (ACC) hypofunction and deficient top-down control system during emotion regulation tasks, despite conflicting techniques and results. Only one study explored the "conditioned fear overgeneralization theory", other the "intolerance of uncertainty model" and two studies were unspecific (worry induction tasks). Between those, there were 4 studies evaluating pre- and post-treatment with antidepressants or "mindfulness". LIMITATIONS: The studies׳ methodologies differ between one another making it difficult to identify a common finding. CONCLUSION: Emotion dysregulation seems to be an important cognitive dysfunction in GAD patients and fMRI studies suggest that it is related to PFC and ACC hypofunction as well as a deficient cortex-amygdala functional connectivity.

Demographics, clinical characteristics and quality of life of Brazilian women with driving phobia.

Driving phobia is associated with serious consequences such as restriction of freedom, career impairments and social embarrassment. The main objective of this paper is to compare clinical characteristics and quality of life between women with driving phobia and women without this phobia. These factors were assessed using structured interviews, semi-structured questionnaires, scales and inventories. We accessed diagnoses, depressive symptoms, anxiety symptoms, anxiety traits, driving cognitions and quality of life. There was no difference between groups with regard to demographic data and driving history. Both groups were also equivalent in the number of traumatic events and accidents experienced while driving or riding. The fear of driving group showed higher state and trait anxiety scores. A high frequency of cognitive distortions can explain why people with driving phobia often engage in maladaptive safety behaviors in an attempt to protect themselves from unpredicted dangers when driving. Regarding quality of life, the control group had slightly higher scores on all subscales, but significant differences were observed for only three scales: "functional capacity", "social aspects", and "mental health". More studies with larger samples more instruments and other contexts are needed to further investigate the clinical characteristics and personality traits of people who have a fear of driving.

A hundred-year of Karl Jaspers' General Psychopathology (Allgemeine Psychopathologie)--1913-2013: a pivotal book in the history of psychiatry.

After a hundred-years of its publication, the Karl Jaspers' book, General Psychopathology, is still an indispensable book to psychiatrists and for all those who study psychopathology. It's a clear delineation of the phenomenological method for describing the symptoms of mental disorders that remains unmatched until nowadays. The book focuses on the relevance of phenomenological and hermeneutical methods in psychopathology. Although this work is grounded in the clinical thought and practices of the late nineteenth and early twentieth centuries, Jaspers' delineation of psychiatric methods in this work is still evaluated as unmatched to this day, a work that is indispensable to contemporary psychiatry. Jaspers also contributed with important articles and book reviews to psychiatric periodicals during the first two decades of the twentieth century.

A hundred-year of Karl Jaspers' General Psychopathology (Allgemeine Psychopathologie) - 1913-2013: a pivotal book in the history of Psychiatry / Cem anos de Psicopatologia Geral (Allgemeine Psychopathologie) de Karl Jaspers - 1913-2013: um livro decisivo na historia da Psiquiatria

After a hundred-years of its publication, the Karl Jaspers' book, General Psychopathology, is still an indispensable book to psychiatrists and for all those who study psychopathology. It's a clear delineation of the phenomenological method for describing the symptoms of mental disorders that remains unmatched until nowadays. The book focuses on the relevance of phenomenological and hermeneutical methods in psychopathology. Although this work is grounded in the clinical thought and practices of the late nineteenth and early twentieth centuries, Jaspers' delineation of psychiatric methods in this work is still evaluated as unmatched to this day, a work that is indispensable to contemporary psychiatry. Jaspers also contributed with important articles and book reviews to psychiatric periodicals during the first two decades of the twentieth century.

Após cem anos de sua publicação, o livro de Karl Jaspers, Psicopatologia Geral, continua sendo uma obra indispensável para psiquiatras e para todos que se dedicam ao estudo de psicopatologia. Seu claro delineamento do método fenomenológico para a descrição dos sintomas dos transtornos mentais permanece intocável até hoje. O livro foca a relevância dos métodos fenomenológico e hermenêutico em psicopatologia. Apesar do trabalho ter sido baseado no pensamento e na prática clínica do final do século XIX e do início do século XX, a delineação dos métodos em psiquiatria de Jaspers é avaliado como ímpar até hoje, um trabalho indispensável para a psiquiatria atual. Jaspers também contribuiu com importantes artigos e revisões de livros para revistas psiquiátricas durante as primeiras duas décadas do século XX.

The panic disorder respiratory ratio: a dimensional approach to the respiratory subtype.

OBJECTIVE: The respiratory ratio is a dimensional construct of the respiratory subtype of panic disorder (PD). The respiratory subtype has been correlated with an increased sensitivity to CO2 inhalation, positive family history of PD and low comorbidity with depression. The objective of our study was to determine whether the respiratory ratio is correlated with CO2-induced panic attacks and other clinical and demographic features. METHODS: We examined 91 patients with PD and submitted them to a double-breath 35% CO2 challenge test. The respiratory ratio was calculated based on the Diagnostic Symptom Questionnaire (DSQ) scores recorded in a diary in the days preceding the CO2 challenge. The scores of the respiratory symptoms were summed and divided by the total DSQ score. RESULTS: The respiratory ratio was correlated with CO2 sensitivity, and there was a non-statistically significant trend towards a correlation with a family history of PD. CONCLUSIONS: The positive correlation between the respiratory ratio and the anxiety elicited by the CO2 inhalation indicates that the intensity of respiratory symptoms may be proportional to the sensitivity to carbon dioxide.

The panic disorder respiratory ratio: a dimensional approach to the respiratory subtype

OBJECTIVE: The respiratory ratio is a dimensional construct of the respiratory subtype of panic disorder (PD). The respiratory subtype has been correlated with an increased sensitivity to CO2 inhalation, positive family history of PD and low comorbidity with depression. The objective of our study was to determine whether the respiratory ratio is correlated with CO2-induced panic attacks and other clinical and demographic features. METHODS: We examined 91 patients with PD and submitted them to a double-breath 35% CO2 challenge test. The respiratory ratio was calculated based on the Diagnostic Symptom Questionnaire (DSQ) scores recorded in a diary in the days preceding the CO2 challenge. The scores of the respiratory symptoms were summed and divided by the total DSQ score. RESULTS: The respiratory ratio was correlated with CO2 sensitivity, and there was a non-statistically significant trend towards a correlation with a family history of PD. CONCLUSIONS: The positive correlation between the respiratory ratio and the anxiety elicited by the CO2 inhalation indicates that the intensity of respiratory symptoms may be proportional to the sensitivity to carbon dioxide.