Brazilian Psychiatric Association guidelines on the integration of spirituality into mental health clinical practice: Part 1. Spiritual history and differential diagnosis

Objectives: To present evidence-based guidelines for clinical practice regarding religiosity and spirituality in mental health care in Brazil. Methods: A systematic review was conducted to identify potentially eligible articles indexed in the PubMed, PsycINFO, SciELO, LILACS, and Cochrane databases. A summary of recommendations and their levels of evidence was produced in accordance with Oxford Centre for Evidence-Based Medicine guidelines. Results: The systematic review identified 6,609 articles, 41 of which satisfied all inclusion criteria. Taking a spiritual history was found to be an essential part of a compassionate and culturally sensitive approach to care. It represents a way of obtaining relevant information about the patient's religiosity/spirituality, potential conflicts that could impact treatment adherence, and improve patient satisfaction. Consistent evidence shows that reported perceptual experiences are unreliable for differentiating between anomalous experiences and psychopathology. Negative symptoms, cognitive and behavioral disorganization, and functional impairment are more helpful for distinguishing pathological and non-pathological anomalous experiences. Conclusion: Considering the importance of religiosity/spirituality for many patients, a spiritual history should be routinely included in mental health care. Anomalous experiences are highly prevalent, requiring a sensitive and evidence-based approach to differential diagnosis.

Brazilian Psychiatric Association guidelines on the integration of spirituality into mental health clinical practice: Part 1. Spiritual history and differential diagnosis.

OBJECTIVES: To present evidence-based guidelines for clinical practice regarding religiosity and spirituality in mental health care in Brazil. METHODS: A systematic review was conducted to identify potentially eligible articles indexed in the PubMed, PsycINFO, SciELO, LILACS, and Cochrane databases. A summary of recommendations and their levels of evidence was produced in accordance with Oxford Centre for Evidence-Based Medicine guidelines. RESULTS: The systematic review identified 6,609 articles, 41 of which satisfied all inclusion criteria. Taking a spiritual history was found to be an essential part of a compassionate and culturally sensitive approach to care. It represents a way of obtaining relevant information about the patient's religiosity/spirituality, potential conflicts that could impact treatment adherence, and improve patient satisfaction. Consistent evidence shows that reported perceptual experiences are unreliable for differentiating between anomalous experiences and psychopathology. Negative symptoms, cognitive and behavioral disorganization, and functional impairment are more helpful for distinguishing pathological and non-pathological anomalous experiences. CONCLUSION: Considering the importance of religiosity/spirituality for many patients, a spiritual history should be routinely included in mental health care. Anomalous experiences are highly prevalent, requiring a sensitive and evidence-based approach to differential diagnosis.

Incidence of adverse events and comparative tolerability of selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for the treatment of anxiety, obsessive-compulsive, and stress disorders: a systematic review and network meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13-83.76) when compared to placebo groups (71.21%, 67.00-75.09). Nausea was the most common adverse event (25.71%, CI 23.96-27.54), while weight change was the least common (3.56%, 1.68-7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Placebo response in trials with patients with anxiety, obsessive-compulsive and stress disorders across the lifespan: a three-level meta-analysis.

QUESTION: Randomised controlled trials assessing treatments for anxiety, obsessive-compulsive and stress-related disorders often present high placebo response rates in placebo groups. Understanding the placebo response is essential in accurately estimating the benefits of pharmacological agents; nevertheless, no studies have evaluated the placebo response across these disorders using a lifespan approach. STUDY SELECTION AND ANALYSIS: We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies and international registers from inception to 9 September 2022. The primary outcome was the aggregate measure of internalising symptoms of participants in the placebo arms of randomised controlled trials designed to assess the efficacy of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) in individuals diagnosed with anxiety, obsessive-compulsive or stress-related disorders. The secondary outcomes were placebo response and remission rates. Data were analysed through a three-level meta-analysis. FINDINGS: We analysed 366 outcome measures from 135 studies (n=12 583). We found a large overall placebo response (standardised mean difference (SMD)=-1.11, 95% CI -1.22 to -1.00). The average response and remission rates in placebo groups were 37% and 24%, respectively. Larger placebo response was associated with a diagnosis of generalised anxiety disorder and post-traumatic stress disorder, when compared with panic, social anxiety and obsessive-compulsive disorder (SMD range, 0.40-0.49), and with absence of a placebo lead-in period (SMD=0.44, 95% CI 0.10 to 0.78). No significant differences were found in placebo response across age groups. We found substantial heterogeneity and moderate risk of bias. CONCLUSIONS: Placebo response is substantial in SSRI and SNRI trials for anxiety, obsessive-compulsive and stress-related disorders. Clinicians and researchers should accurately interpret the benefits of pharmacological agents in contrast to placebo response. PROSPERO REGISTRATION NUMBER: CRD42017069090.

Validation and clinical application of the Metacognitions Questionnaire in a sample of Brazilian generalized anxiety disorder patients: the effects of different treatment interventions.

INTRODUCTION: Metacognitive beliefs about worry may trigger anxiety. However, the effect of generalized anxiety disorder (GAD) treatment on metacognition has not yet been investigated. OBJECTIVES: To validate the Metacognitions Questionnaire (MCQ-30) in a Brazilian GAD sample and verify whether different interventions reduce metacognitive beliefs. METHOD: We recruited 180 GAD individuals and randomized them to Body in Mind Training (BMT), Fluoxetine (FLX), or an active control group (Quality of Life [QoL]) for 8 weeks. The MCQ-30 was assessed for internal consistency, was evaluated with confirmatory and exploratory factor analyses, and was tested for convergent validity with the Penn State Worry Questionnaire (PSWQ). Generalized estimating equations (GEE) were employed to analyze differences after the interventions. RESULTS: The MCQ-30 demonstrated good internal consistency and acceptability; the original five-factor model was supported. There was a positive moderate correlation between MCQ-30 scores and worry. GEE showed a significant group x time interaction (p < 0.001). Both BMT (mean difference [MD] = -6.04, standard error [SE] = -2.39, p = 0.034) and FLX (MD = -5.78, SE = 1.91, p = 0.007) reduced MCQ-30 scores. FLX was superior to QoL, but not BMT, at weeks 5 and 8. There were no differences between BMT and QoL. CONCLUSION: The Brazilian-Portuguese version of MCQ-30 showed good psychometric properties. Furthermore, the positive effect of FLX and BMT on metacognition suggests it may represent a potential therapeutic target.

Emotional eating in women with generalized anxiety disorder.

INTRODUCTION: Individuals diagnosed with generalized anxiety disorder (GAD) seek pleasurable foods to avoid their negative emotional experiences. Ineffective regulation of negative emotions may be a risk factor for emotional eating (EE), leading to suffering, dysfunctional behaviors, and weight gain. OBJECTIVES: The aim of this study is to understand the relationship between emotional dysregulation and EE, investigating potential mediators such as the intensity of the worry, avoidance of internal experiences, mindfulness, and self-compassion in female patients with anxiety. METHODS: In this cross-sectional study, participants from a randomized clinical trial diagnosed with GAD answered the following instruments at baseline: the Difficulties in Emotion Regulation Scale (DERS), the Three Factor Eating Questionnaire (TFEQ-R21), the Penn State Worry Questionnaire (PSWQ), the Action and Acceptance Questionnaire (AAQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Self-Compassion Scale (SCS). We estimated Pearson correlation coefficients and performed mediation analyses. RESULTS: We evaluated 51 female individuals, 34 of whom completed all the questionnaires. Our data showed that EE was positively correlated with emotional dysregulation (r = 0.593; p < 0.001), worry trait (r = 0.402; p = 0.018), and avoidance of internal experiences (r = 0.565; p < 0.001), whereas it was negatively correlated with self-compassion (r = -0.590; p < 0.001) and mindful state (r = -0.383; p = 0.026). Moreover, we demonstrated that self-compassion mediates the relationship between emotional dysregulation and EE (ab product estimate = 0.043, 95% confidence interval [95%CI] 0.003-0.084). CONCLUSION: Our findings contribute to the literature by identifying psychological factors that could mediate the association between emotional dysregulation and EE, enabling identification of more effective eating behavior intervention targets for patients with GAD.

Mechanisms of improvement in generalized anxiety disorder: A mediation and moderated mediation analysis from a randomized controlled trial.

BACKGROUND: Generalized anxiety disorder (GAD) is associated with the lowest treatment response rate among all anxiety disorders. Understanding mechanisms of improvement may help to develop more effective and personalized treatments. AIM: The objective of the study was to investigate different improvement mechanisms in the treatment of individuals diagnosed with GAD. DESIGN: We reported data from a randomized controlled trial that evaluated three different GAD treatments (mindfulness-based intervention, BMT; fluoxetine, FLX; and an active comparison group, QoL) for 8 weeks. METHOD: Mediation analyses were performed evaluating the association between worry symptoms at baseline and anxiety scoring at the endpoint, considering self-compassion or mindfulness or its dimensions at mid-treatment as mediators for the whole sample (assessing GAD improvement mechanism) and the different interventions as moderators. RESULTS: Contrary to mindfulness state scoring (C = .06; 95% CI = -.05 to .20), self-compassion (C = .11; 95% CI = .01 to .28) and non-judgement of inner experience (C = .10; 95% CI = .004 to .21) mediated the association between worry symptoms at baseline and anxiety at the endpoint. When comparing BMT to FLX, the intervention modality did not moderate these associations. CONCLUSION: Self-compassion and non-judgement of inner experience seem to be essential targets in GAD treatment, contrary to the mindfulness state itself. Although no difference was found considering the intervention modality, future research may assess how to boost these dimensions in specific treatments for GAD.

Early emotional memories and bonding as predictors of short-term and long-term outcome in adults with generalized anxiety disorder.

The impact of childhood experiences on the development of psychopathology is well established in the literature. Few studies, however, have assessed parental bonding during childhood as a predictor of response to anxiety disorders treatment. The aim of the study was to examine whether emotional memories of childhood parenting could predict short-term and long-term outcome in three different interventions for patients with generalized anxiety disorder (GAD): mindfulness-based intervention (Body in Mind Training [BMT]), fluoxetine (FLX), and an active control group (quality of life [QoL]). A total of 124 participants from a randomized controlled trial for GAD treatment were evaluated pre- and post-treatment and after 18 months. Patients were assessed for the severity of GAD symptoms (GAD-7, PSWQ, and DERS), early memories of warmth and safeness (EMWSS), and recall of perceived threat and subordination/submission in childhood (ELES). Negative childhood memories predicted a greater reduction in anxiety symptoms on BMT treatment compared to FLX and QoL, whereas positive childhood memories predicted more symptomatic improvement in the QoL group. Our findings suggest that individuals with GAD who have early memories of subordination and threat appear to benefit more from interventions that focus on developing emotion-regulation strategies and enhancing self-compassion, such as mindfulness-based interventions.

Emotional eating in women with generalized anxiety disorder

Abstract Introduction Individuals diagnosed with generalized anxiety disorder (GAD) seek pleasurable foods to avoid their negative emotional experiences. Ineffective regulation of negative emotions may be a risk factor for emotional eating (EE), leading to suffering, dysfunctional behaviors, and weight gain. Objectives The aim of this study is to understand the relationship between emotional dysregulation and EE, investigating potential mediators such as the intensity of the worry, avoidance of internal experiences, mindfulness, and self-compassion in female patients with anxiety. Methods In this cross-sectional study, participants from a randomized clinical trial diagnosed with GAD answered the following instruments at baseline: the Difficulties in Emotion Regulation Scale (DERS), the Three Factor Eating Questionnaire (TFEQ-R21), the Penn State Worry Questionnaire (PSWQ), the Action and Acceptance Questionnaire (AAQ), the Five Facet Mindfulness Questionnaire (FFMQ), and the Self-Compassion Scale (SCS). We estimated Pearson correlation coefficients and performed mediation analyses. Results We evaluated 51 female individuals, 34 of whom completed all the questionnaires. Our data showed that EE was positively correlated with emotional dysregulation (r = 0.593; p < 0.001), worry trait (r = 0.402; p = 0.018), and avoidance of internal experiences (r = 0.565; p < 0.001), whereas it was negatively correlated with self-compassion (r = -0.590; p < 0.001) and mindful state (r = -0.383; p = 0.026). Moreover, we demonstrated that self-compassion mediates the relationship between emotional dysregulation and EE (ab product estimate = 0.043, 95% confidence interval [95%CI] 0.003-0.084). Conclusion Our findings contribute to the literature by identifying psychological factors that could mediate the association between emotional dysregulation and EE, enabling identification of more effective eating behavior intervention targets for patients with GAD.

Validation and clinical application of the Metacognitions Questionnaire in a sample of Brazilian generalized anxiety disorder patients: the effects of different treatment interventions

Abstract Introduction Metacognitive beliefs about worry may trigger anxiety. However, the effect of generalized anxiety disorder (GAD) treatment on metacognition has not yet been investigated. Objectives To validate the Metacognitions Questionnaire (MCQ-30) in a Brazilian GAD sample and verify whether different interventions reduce metacognitive beliefs. Method We recruited 180 GAD individuals and randomized them to Body in Mind Training (BMT), Fluoxetine (FLX), or an active control group (Quality of Life [QoL]) for 8 weeks. The MCQ-30 was assessed for internal consistency, was evaluated with confirmatory and exploratory factor analyses, and was tested for convergent validity with the Penn State Worry Questionnaire (PSWQ). Generalized estimating equations (GEE) were employed to analyze differences after the interventions. Results The MCQ-30 demonstrated good internal consistency and acceptability; the original five-factor model was supported. There was a positive moderate correlation between MCQ-30 scores and worry. GEE showed a significant group x time interaction (p < 0.001). Both BMT (mean difference [MD] = -6.04, standard error [SE] = -2.39, p = 0.034) and FLX (MD = -5.78, SE = 1.91, p = 0.007) reduced MCQ-30 scores. FLX was superior to QoL, but not BMT, at weeks 5 and 8. There were no differences between BMT and QoL. Conclusion The Brazilian-Portuguese version of MCQ-30 showed good psychometric properties. Furthermore, the positive effect of FLX and BMT on metacognition suggests it may represent a potential therapeutic target.

Habituating to pandemic anxiety: Temporal trends of COVID-19 anxiety over sixteen months of COVID-19.

The impact of COVID-19 anxiety on mental health and its association with preventive measures is well-established. We aimed to study how COVID-19 anxiety and its dimensions vary over time (16 months) in a sample of individuals (N = 2717) suffering from mental distress in the pandemic context that participated in a randomized clinical trial testing psychosocial interventions in Brazil. Results showed that pandemic anxiety reduced over time. COVID-19 influences fear of others being infected and concerns about mental health being affected by COVID-19 were more significant than the fear of being infected or the physical health influenced by COVID-19. A similar temporal effect was not found for burnout, and this effect was not correlated with the number of COVID-related deaths. Habituation to pandemic anxiety or higher intolerance of uncertainty at the beginning of the pandemic is putative mechanisms for the patterns observed in the data. They might have implications for mental health interventions in the pandemic scenario and motivational strategies for prevention. TRIAL REGISTRATION NUMBER: Plataforma Basil (CAAE: 30608420.5.0000.5327), ClinicalTrials.gov (NCT04632082; November 17, 2020).

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.

Heart rate variability as a predictor of improvement in emotional interference in Generalized Anxiety Disorder.

BACKGROUND: Generalized anxiety disorder (GAD) is one of the most prevalent anxiety disorders but the least successfully treated. The search for accessible clinical, psychological and biological markers is crucial for developing more effective and personalized interventions. AIMS: To evaluate if changes in heart rate variability (HRV) between rest and stress conditions before interventions could predict improvement in emotional interference (EI) in a cognitive task after three different treatment modalities in patients with GAD. METHOD: This is a post-hoc analysis study reporting data from a larger randomized controlled trial (NCT03072264) assessing a mindfulness-based intervention (BMT), fluoxetine (FLX), and an active comparison group (QoL) in adult patients diagnosed with GAD. We assessed pulse plethysmography (PPG) data using a Shimmer3 GSR to measure HRV. Regression analyses were performed using the variation between baseline and endpoint EI scores as dependent variables and contrasts considering changing in HRV*group interaction in the baseline. RESULTS: 106 individuals were included. The correlations between HRV changing from rest to task predicted improvement in IE only in the FLX versus control group contrast (estimated = -80.24; SE = 27.31; p = 0.005) and not in the BMT and control group contrast. CONCLUSION: More flexible HRV at baseline predicted EI improvement only in the FLX group. This finding is clinically relevant since it may help us develop more personalized interventions for GAD.

Selective serotonin reuptake inhibitors, and serotonin and norepinephrine reuptake inhibitors for anxiety, obsessive-compulsive, and stress disorders: A 3-level network meta-analysis.

BACKGROUND: Anxiety, obsessive-compulsive, and stress-related disorders frequently co-occur, and patients often present symptoms of several domains. Treatment involves the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs), but data on comparative efficacy and acceptability are lacking. We aimed to compare the efficacy of SSRIs, SNRIs, and placebo in multiple symptom domains in patients with these diagnoses over the lifespan through a 3-level network meta-analysis. METHODS AND FINDINGS: We searched for published and unpublished randomized controlled trials that aimed to assess the efficacy of SSRIs or SNRIs in participants (adults and children) with diagnosis of any anxiety, obsessive-compulsive, or stress-related disorder in MEDLINE, PsycINFO, Embase, and Cochrane Library from inception to 23 April 2015, with an update on 11 November 2020. We supplemented electronic database searches with manual searches for published and unpublished randomized controlled trials registered in publicly accessible clinical trial registries and pharmaceutical companies' databases. No restriction was made regarding comorbidities with any other mental disorder, participants' age and sex, blinding of participants and researchers, date of publication, or study language. The primary outcome was the aggregate measure of internalizing symptoms of these disorders. Secondary outcomes included specific symptom domains and treatment discontinuation rate. We estimated standardized mean differences (SMDs) with 3-level network meta-analysis with random slopes by study for medication and assessment instrument. Risk of bias appraisal was performed using the Cochrane Collaboration's risk of bias tool. This study was registered in PROSPERO (CRD42017069090). We analyzed 469 outcome measures from 135 studies (n = 30,245). All medications were more effective than placebo for the aggregate measure of internalizing symptoms (SMD -0.56, 95% CI -0.62 to -0.51, p < 0.001), for all symptom domains, and in patients from all diagnostic categories. We also found significant results when restricting to the most used assessment instrument for each diagnosis; nevertheless, this restriction led to exclusion of 72.71% of outcome measures. Pairwise comparisons revealed only small differences between medications in efficacy and acceptability. Limitations include the moderate heterogeneity found in most outcomes and the moderate risk of bias identified in most of the trials. CONCLUSIONS: In this study, we observed that all SSRIs and SNRIs were effective for multiple symptom domains, and in patients from all included diagnostic categories. We found minimal differences between medications concerning efficacy and acceptability. This three-level network meta-analysis contributes to an ongoing discussion about the true benefit of antidepressants with robust evidence, considering the significantly larger quantity of data and higher statistical power when compared to previous studies. The 3-level approach allowed us to properly assess the efficacy of these medications on internalizing psychopathology, avoiding potential biases related to the exclusion of information due to distinct assessment instruments, and to explore the multilevel structure of transdiagnostic efficacy.

A Three-Arm Randomized Clinical Trial Comparing the Efficacy of a Mindfulness-Based Intervention with an Active Comparison Group and Fluoxetine Treatment for Adults with Generalized Anxiety Disorder.

INTRODUCTION: Mindfulness-based interventions have been studied as an alternative treatment for anxiety disorders, but there are only a few studies comparing these with established treatments. OBJECTIVE: To evaluate the efficacy of a Body in Mind Training (BMT) program for adults with generalized anxiety disorder (GAD), an active comparison protocol called Quality of Life and Psychoeducation (QoL), and treatment with fluoxetine (FLX). METHODS: This study comprises a 3-arm parallel-group, randomized clinical trial (ClinicalTrials.gov ID: NCT03072264). Adults with a primary diagnosis of GAD and no current treatment were recruited from the community and randomized in a ratio 1:1:1. The primary outcomes were assessed by means of the Hamilton Anxiety Rating Scale (HAM-A) and the Penn State Worry Questionnaire (PSWQ) at week 8. Data were analyzed using a superiority analysis (BMT vs. QoL) and a noninferiority analysis (BMT vs. FLX). RESULTS: A total of 249 participants were included and 223 were analyzed (76 BMT, 79 FLX, and 68 QoL). All groups improved after intervention. However, BMT was not superior to QoL at week 8 (mean difference = -1.36; p = 0.47), nor was it noninferior to FLX as assessed with theHAM-A (mean difference = 3.5; 95% CI -0.06 to 7.06; noninferiority margin = -2.43; p = 0.054). QoL (mean difference = 3.54; p = 0.04) and FLX (mean difference = -7.72; 95% CI -10.89 to -4.56; noninferiority margin = -2.09; p < 0.001) were superior to BMT in reducing PSWQ score. CONCLUSION: Our data suggest that BMT, in its current format, cannot be considered an effective mindfulness protocol to improve GAD.

Cytokine Levels in Panic Disorder: Evidence for a Dose-Response Relationship.

OBJECTIVE: Several studies have investigated possible biological correlates of mental disorders. Although some studies have consistently reported elevated levels of serum inflammatory markers in depression, very few have evaluated cytokine levels in patients with lifetime panic disorder (PD). METHODS: Seventy-eight adults (75% women) from an anxiety disorders outpatient unit were categorized according to their PD status: current or in remission. Serum levels of interleukin (IL)-6, tumor necrosis factor α, and IL-10 were evaluated using flow cytometry with enhanced sensitivity flex sets. Data on clinical comorbidity, lipid profile, fasting blood glucose, C-reactive protein, and PD severity were also obtained. RESULTS: Significantly higher mean levels of serum IL-6 (0.83 vs 0.60 pg/mL [95% confidence interval {CI}for the log-transformed mean difference, -0.41 to -0.57], p = .008) but not of tumor necrosis factor-α (0.18 vs 0.14 pg/mL [95% CI, -1.12 to 0.11]; p = 0.53) or IL-10 (0.21 vs 0.26 [95% CI, -0.20 to 0.44]; p = 0.16), were associated with current PD compared to remitted PD. Higher Panic Disorder Severity Scale (standardized ß = 0.36; p = .013), body mass index (standardized ß = 0.53, p < .001) and fasting blood glucose 5.6 mmol/L or greater (standardized ß = 0.23, p = .038) were significantly associated with higher levels of IL-6 in the multivariate linear regression model. CONCLUSIONS: Our findings support a proinflammatory state in patients with current PD that is independent of possible confounders. Although there are important implications of these findings, replication is required.