Resilience and coping strategies in cognitive behavioral group therapy for patients with panic disorder.

BACKGROUND: Although resilience and coping are important factors associated with mental health, they are rarely investigated in the treatment of patients with panic disorder (PD). OBJECTIVE: To evaluate the response to four resilience and coping strategy sessions added to the standard cognitive behavioral group therapy (CBGT) protocol for PD. DESIGN: Controlled clinical trial. METHODS: The control group (n = 50) attended 12 CBGT sessions, while the intervention group (n = 50) received four additional resilience and coping strategy sessions, i.e., 16 in total. Symptom severity, resilience, coping strategies, and quality of life were assessed at baseline and post-CBGT. RESULTS: Symptom severity and maladaptive coping strategies decreased significantly in both groups. However, the intervention group had increased resilience and improvement in the environment domain of quality of life. CONCLUSIONS: Additional sessions have potential benefits for coping skills and resilience in PD patients, but these benefits should be evaluated in further long-term studies.

Effect of cognitive-behavioral group therapy for panic disorder in changing coping strategies.

BACKGROUND: Cognitive-behavioral group therapy (CBGT) is an efficient treatment for panic disorder (PD). However, the role of CBGT in enhancing strategies to cope with stressful events has not been established. AIM: To evaluate the effect of CBGT on the choice of coping strategy by PD patients compared to a group of individuals without mental disorders. METHODS: Forty-eight PD patients who completed a 12-session CBGT protocol were compared to 75 individuals without mental disorders regarding coping strategies as evaluated by the Coping Strategies Inventory (CSI). The severity of PD was assessed at baseline and after CBGT through the Clinical Global Impression (CGI) scale, the Hamilton Anxiety Scale (HAM-A), and the Panic Inventory (PI). RESULTS: Treatment was effective in reducing PD severity in all outcome measures. Patients used significantly fewer confrontation, escape and avoidance strategies after CBGT. The use of more adaptive coping strategies was related to a decrease in panic attacks and anticipatory anxiety. Application of the CSI showed that the use of strategies was also significantly different in patients as compared to the control group, except for escape and avoidance, which became similar after the CBGT protocol. CONCLUSIONS: Despite the changes observed after the CBGT protocol, the choice of coping strategy was still different in patients vs. controls. The current CBGT protocol was used specifically to assess PD symptoms. Other cognitive tools should be included to address maladaptive coping strategies.

Preliminary evidence of association between EFHC2, a gene implicated in fear recognition, and harm avoidance.

Genetic variation at the EF-hand domain containing 2 gene (EFHC2) locus has been associated with fear recognition in Turner syndrome. The aim of this study was to examine whether EFHC2 variants are associated with non-syndromic anxiety-related traits [harm avoidance (HA) and behavioral inhibition (BI)] and with panic disorder (PD). Our sample comprised 127 PD patients and 132 controls without psychiatric disorder. We genotyped nine SNPs within the EFHC2 locus and used PLINK to perform association analyses. An intronic SNP (rs1562875) was associated with HA (permuted p=0.031) accounting alone for over 3% of variance in this trait. This same SNP was nominally, but not empirically, associated with BI (r(2)=0.022; nominal p=0.022) and PD (OR=2.64; nominal p=0.009). The same association was found in a subsample of only females. In sum, we observed evidence of association between a variant in EFHC2, a gene previously associated with the processing of fear and social threat, and HA. Larger studies are warranted to confirm this association.

Lack of association between the serotonin transporter promoter polymorphism (5-HTTLPR) and personality traits in asymptomatic patients with panic disorder.

The serotonin transporter promoter polymorphism (5-HTTLPR) has been investigated regarding its association with neuroticism, which, in its turn, is a personality dimension often found in patients with panic disorder (PD). It has been recently evidenced that the long 5-HTTLPR polymorphism has a genetic variation (Lg), which is related to its lower expression. The objective of this study was to assess the association between the 5-HTTLPR polymorphism in the triallelic system and the neurotic personality traits in patients in PD remission. Sixty-seven Caucasian patients with PD diagnosis according to the DSM-IV-TR assessed with the MINI (mini international neuropsychiatric interview) were included. The MMPI (Minnesota multiphasic personality inventory) was used to assess the personality. The remission of PD symptoms was defined as CGI (clinical global impression)

Harm avoidance and self-directedness as essential features of panic disorder patients.

OBJECTIVE: The purpose of the study is to compare the personality traits assessed with the Temperament and Character Inventory (TCI) between patients with panic disorder (PD) and a control group in a Brazilian sample. METHODS: One hundred thirty-five patients with PD paired according to sex and age with 135 controls without any psychiatric disorders were assessed with the Mini International Neuropsychiatric Interview (MINI), a structured interview. Temperament and character were assessed with the TCI. RESULTS: Consistently, patients with PD presented higher scores on the harm avoidance (HA) temperament scale (23.20 +/- 5.41 vs 15.21 +/- 4.92; P < .001) and lower scores on the self-directedness (SD) (27.81 +/- 7.25 vs 35.16 +/- 5.47; P < .001) if compared to the control group and has been associated independently from other TCI scales and confounders with PD. The multivariate logistic model containing HA and SD explains 38.6% to 51.4% of the differences between PD and controls. CONCLUSIONS: Harm avoidance could be a good candidate to be heritable because it appears to be a consistent finding across current literature in anxious and depressed patients independent of their cultural context. Also, SD seems to be a key character characteristic of PD patients. The dimensional assessment is an interesting alternative for understanding the relationship between the psychobiologic bases of temperament and character and is highly related to the development of psychiatric syndromes.

Lack of association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder: a systematic review and meta-analysis.

BACKGROUND: The aim of this study is to assess the association between the Serotonin Transporter Promoter Polymorphism (5-HTTLPR) and Panic Disorder (PD). METHODS: This is a systematic review and meta-analysis of case-control studies with unrelated individuals of any ethnic origin examining the role of the 5-HTTLPR in PD according to standard diagnostic criteria (DSM or ICD). Articles published in any language between January 1996 and April 2007 were eligible. The electronic databases searched included PubMed, PsychInfo, Lilacs and ISI. Two separate analyses were performed: an analysis by alleles and a stratified analysis separating studies by the quality of control groups. Asymptotic DerSimonian and Laird's Q test were used to assess heterogeneity. Results of individual studies were combined using the fixed effect model with respective 95% confidence intervals. RESULTS: Nineteen potential articles were identified, and 10 studies were included in this meta-analysis. No statistically significant association between 5-HTTLPR and PD was found, OR = 0.91 (CI95% 0.80 to 1.03, p = 0.14). Three sub-analyses divided by ethnicity, control group quality and Agoraphobia comorbidity also failed to find any significant association. No evidence of heterogeneity was found between studies in the analyses. CONCLUSION: Results from this systematic review do not provide evidence to support an association between 5-HTTLPR and PD. However, more studies are needed in different ethnic populations in order to evaluate a possible minor effect.

The efficacy of milnacipran in panic disorder: an open trial.

The aim of this study is to evaluate the efficacy of milnacipran in the acute treatment of patients with panic disorder. Thirty-one patients who met Diagnostic and statistical manual of mental disorders-IV criteria for panic disorder with or without agoraphobia were included in the study. Patients were initially treated with milnacipran 25 mg twice daily and then 50 mg twice daily until the 10th week. The treatment outcome and panic disorder severity were determined by the Panic Disorder Severity Scale, Panic Inventory, Clinical Global Impression and Hamilton Anxiety Scale, all of which were applied during every evaluation interview. Quality of life (WHOQOL-bref) was evaluated at baseline and at the end of the study. Missing data were handled by using the last observation carried forward for all participants who had taken at least one dose of study medication. Intention-to-treat was used in the analyses. Pharmacological treatment resulted in a clinically and statistically significant mean reduction in all severity measures. Remission (Clinical Global Impression < or = 2) was obtained in 58.1% of the sample. Regarding WHOQOL, we found a significant improvement (P<0.05) across treatment in all the domains studied. Although results may be influenced by the open design of this pilot study and by the small sample size, our findings suggest that milnacipran may be effective for the treatment of panic disorder and justify further research.

Trauma and defense style as response predictors of pharmacological treatment in panic patients.

BACKGROUND: As panic disorder (PD) has a chronic course, it is important to identify predictors that might be related to non-remission. The aim of this study is to verify whether history of trauma and defense style are predictors to pharmacological treatment response in PD patients. METHOD: The sample was composed by 47 PD patients according to DSM-IV who were treated with sertraline for 16 weeks. Evaluations were assessed by the C.G.I. (Clinical Global Impression), the Hamilton-Anxiety Scale, the Hamilton-Depression Scale, the Panic Inventory and the DSQ-40 (Defense Style Questionnaire) at baseline and after treatment. RESULTS: Full remission was observed in 61.7% of the sample. The predictors significantly associated with non-remission were: severity of PD (p=0.012), age of onset (p=0.02) and immature defenses (p=0.032). In addition, the history of trauma was associated with early onset of PD (p=0.043). CONCLUSION: Panic patients had as predictors of worse response to pharmacological treatment the early onset and the severity of PD symptoms as well as the use of immature defenses at baseline. This finding corroborates the relevance of the evaluation of factors that might affect the response so as to enable the development of appropriate treatment for each patient.

One-year follow-up of pharmacotherapy-resistant patients with panic disorder treated with cognitive-behavior therapy: Outcome and predictors of remission.

Non-response to pharmacotherapy for panic disorder (PD) is a well-documented problem. However, little information exists to guide next-step strategies for these non-responders. In addition to pharmacologic augmentation strategies, several studies support the efficacy of cognitive-behavior therapy (CBT) for these patients, although data on long-term outcomes has been lacking. In this study, we provide one-year outcomes on a sample of 63 patients who completed group CBT for PD after failing to respond adequately to previous pharmacotherapy. Sustained significant benefit was found for all dimensional outcome scores, and nearly two-thirds of the sample met remission criteria. This occurred with reductions in medication use over the follow-up period. Negative predictors of remission status included comorbid dysthymia, social phobia, and generalized anxiety disorder. These results provide additional evidence for the efficacy of CBT for medication non-responders with PD.

Do defense mechanisms vary according to the psychiatric disorder?

OBJECTIVE: The aim of this study was to evaluate the defense mechanisms used by depressive and anxious patients without comorbidities compared to those used by controls and to determine whether these patterns differ between diagnoses. METHOD: The sample was composed of 167 psychiatric patients and 36 controls that were evaluated using the Defense Style Questionnaire 40. All subjects were evaluated through a clinical interview, and each evaluation was confirmed through the application of the Mini International Neuropsychiatric Interview, a structured psychiatric interview. We used ANOVA and discriminant analysis to assess differences between groups. RESULTS: Neurotic defense mechanisms discriminated controls from all patients except those with social anxiety. Immature defense mechanisms differentiated controls from all patients, as well as distinguished depressive patients from panic disorder and obsessive disorder patients. The discriminant analysis indicated that depressive patients are characterized by projection, panic disorder patients by sublimation and obsessive-compulsive patients by acting out. CONCLUSIONS: Depressive and anxious patients differ from other individuals in their use of defense mechanisms, and each diagnosis has a particular pattern. These findings could lead to the development of specific psychotherapeutic interventions.

Quality of Life and Aesthetic Plastic Surgery: A Systematic Review and Meta-analysis.

Quality of life (QoL) is an important outcome in plastic surgery. However, authors use different scales to address this subject, making it difficult to compare the outcomes. To address this discrepancy, the aim of this study was to perform a systematic review and a random effect meta-analysis. METHODS: The search was made in two electronic databases (LILACS and PUBMED) using Mesh and non-Mesh terms related to aesthetic plastic surgery and QoL. We performed qualitative and quantitative analyses of the gathered data. We calculated a random effect meta-analysis with Der Simonian and Laird as variance estimator to compare pre- and postoperative QoL standardized mean difference. To check if there is difference between aesthetic surgeries, we compared reduction mammoplasty to other aesthetic surgeries. RESULTS: Of 1,715 identified, 20 studies were included in the qualitative analysis and 16 went through quantitative analysis. The random effect of all aesthetic surgeries shows that QoL improved after surgery. Reduction mammoplasty has improved QoL more than other procedures in social functioning and physical functioning domains. CONCLUSIONS: Aesthetic plastic surgery increases QoL. Reduction mammoplasty seems to have better improvement compared with other aesthetic surgeries.

Behavioral inhibition and history of childhood anxiety disorders in Brazilian adult patients with panic disorder and social anxiety disorder.

PURPOSE: To evaluate the presence of behavioral inhibition and anxiety disorders during childhood in Brazilian adult patients with panic disorder and social anxiety disorder compared to a control group. METHODS: Fifty patients with panic disorder, 50 patients with social anxiety disorder, and 50 control subjects were included in the study. To assess the history of childhood anxiety, the Schedule for Affective Disorders and Schizophrenia for School Age Children, Epidemiologic Version (K-SADS-E), and the Diagnostic Interview for Children and Adolescents-Parent Version (DICA-P) were used. The presence of behavioral inhibition in childhood was assessed by the self-reported scale of Behavioral Inhibition Retrospective Version (RSRI-30). RESULTS: Patients showed significantly higher prevalence of anxiety disorders and behavioral inhibition in childhood compared to the control group. Patients with social anxiety disorder also showed significantly higher rates of avoidance disorder (46% vs. 18%, p = 0.005), social anxiety disorder (60% vs. 26%, p = 0.001), presence of at least one anxiety disorder (82% vs. 56%, p = 0.009) and global behavioral inhibition (2.89 +/- 0.61 vs. 2.46 +/- 0.61, p < 0.05) and school/social behavioral inhibition (3.56 +/- 0.91 vs. 2.67 +/- 0.82, p < 0.05) in childhood compared to patients with panic disorder. CONCLUSION: Our data are in accordance to the literature and corroborates the theory of an anxiety diathesis, suggesting that a history of anxiety disorders in childhood is associated with an anxiety disorder diagnosis, mainly social anxiety disorder, in adulthood.

What can HPA axis-linked genes tell us about anxiety disorders in adolescents?

INTRODUCTION: Anxiety disorders (AD) share features of both anxiety and fear linked to stress response. The hypothalamic-pituitary-adrenal (HPA) axis is considered the core biological pathway of the stress system and it is known that an inappropriate response to environmental stimuli may be related to individual genetic vulnerability in HPA-linked genes. Despite the biological plausibility of a relationship between the HPA axis and AD, few studies have investigated associations between genetic polymorphisms linked to the HPA axis and this complex disorder. OBJECTIVE: To investigate whether AD are associated with genetic polymorphisms in HPA-linked genes in adolescents. METHODS: Our study consisted of a cross-sectional evaluation of a community sample comprising a total of 228 adolescents (131 cases of AD). We extracted DNA from saliva and genotyped polymorphisms in HPA-linked genes (FKBP5: rs3800373, rs9296158, rs1360780, rs9470080 and rs4713916; NR3C1: rs6198; CRHR1: rs878886; and SERPINA6: rs746530) with real time polymerase chain reaction (PCR). The instruments used to diagnose and assess the severity of AD were the Schedule for Affective Disorder and Schizophrenia for School-Age Children - Present and Lifetime (K-SADS-PL) and the Screen for Child and Anxiety related Emotional Disorders (SCARED). RESULTS: We failed to detect any associations between AD and genetic polymorphisms in HPA-linked genes (p > 0.05). CONCLUSION: To our knowledge, this is the first study evaluating these specific polymorphisms in relation to AD in adolescents, which encourages us to design further research on the subject.

Relationship between adult social phobia and childhood anxiety.

OBJECTIVE: The aim of this study was to evaluate the prevalence of traumas and the presence of childhood anxiety disorders in adult patients with social phobia and investigate their influence on the presentation of the disorder. METHODS: Twenty-four adult patients with social phobia were asked about the presence of trauma before the age of 16. The K-SADS-E and the DICA-P interviews were used to assess these patients regarding childhood anxiety disorders. RESULTS: Twelve (50%) patients reported a history of trauma before the age of 16. The presence of trauma did not influence the presentation of the disorder. Seventy-five percent of patients had a history of anxiety disorders in childhood. Patients with a history of at least 2 childhood anxiety disorders had an increased lifetime prevalence of major depression (10 vs. 3; p=.04) and family history of psychiatric disorders (13 vs. 6; p=.02). CONCLUSION: Anxiety disorder in childhood is associated with family history of psychiatric disorders. The presence of more than one diagnosis of anxiety disorder in childhood can be considered a risk factor for the development of depression in adult patients with social phobia.

[Brazilian-Portuguese version of the Defense Style Questionnaire (DSQ-40) for defense mechanisms measure: a preliminary study]. / Versão em português do Defense Style Questionaire (DSQ-40) para avaliação dos mecanismos de defesa: um estudo preliminar.

UNLABELLED: The aim of this study is to describe the translation and adaptation process of the Defense Style Questionnaire (DSQ-40) into Brazilian-Portuguese version. The instrument has also contended validation evaluation. METHODS: The first version of the scale was presented to five individuals with different schooling for language adaptation. Afterwards the instrument was presented to three experts that evaluated its content validation. The final version was back-translated and accepted by the original author. RESULTS: Vocabulary adjustments were needed in 9 items and language adaptation in 4 items in order to render the final DSQ-40 Brazilian-Portuguese version. The mean of experts' correlation to each defense was 89%, being 100% to mature, neurotic and immature factors. CONCLUSION: The adaptation of DSQ-40 by different individuals and the group of experts enabled the necessary adjustment to the Brazilian socio-cultural reality.

Anxiety disorders and anxiety-related traits and serotonin transporter gene-linked polymorphic region (5-HTTLPR) in adolescents: case-control and trio studies.

The role of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) in anxiety disorder and anxiety-related traits is controversial. Besides this study, few studies have evaluated the triallelic genotype in adolescents. The aim of this study was to investigate whether anxiety disorders and anxiety-related traits are associated with 5-HTTLPR (biallelic and triallelic) in adolescents, integrating both case-control-based and family-based designs in a community sample. This is a cross-sectional community study of 504 individuals and their families: 225 adolescents (129 adolescents with anxiety disorder and 96 controls) and their biological families. We assessed psychiatric diagnosis using the Kiddie Schedule for Affective Disorders and Schizophrenia. The Temperament and Character Inventory and the Resnick Behavioral Inhibition Scale were used to evaluate harm avoidance and behavioral inhibition. DNA was extracted from saliva and genotyped, including biallelic and triallelic 5-HTTLPR classification, by PCR-RFLP followed by agarose gel electrophoresis. We were not able to find any associations between 5-HTTLPR and anxiety-related phenotypes in both case-control and trio analyses. Further investigation and meta-analytic studies are needed to better clarify the inconsistent results with regard to the association between 5-HTTLPR and anxiety-related phenotypes in adolescents.

Mineralocorticoid receptor genotype moderates the association between physical neglect and serum BDNF.

The objective of this study is to investigate if a polymorphism in the NR3C2 gene moderates the association between childhood trauma on serum levels of brain derived neurothrophic factor (sBDNF). sBDNF was used here as a general marker of alteration in brain function. This is a community cross sectional study comprising 90 adolescents (54 with anxiety disorders). DNA was extracted from saliva in order to genotype the MR-2G/C (rs2070951) polymorphism using real time PCR. Blood was collected for sBDNF Elisa immunoassay. The Childhood Trauma Questionnaire (CTQ) was used to evaluate childhood abuse and neglect. Main effects and gene environment interactions were tested using linear regression models. Anxiety disorders were not associated with the MR-2G/C polymorphism or with sBDNF levels, but the number of C alleles of the MR-2G/C polymorphism was significantly associated with higher sBDNF levels (b = 8.008; p-value = 0.001). Subjects with intermediate and high exposure to physical neglect showed higher sBDNF levels if compared to subjects non-exposed (b = 11.955; p = 0.004 and b = 16.186; p = 0.009, respectively). In addition, we detected a significant physical neglect by MR-2G/C C allele interaction on sBDNF levels (p = 0.005), meaning that intermediate and high exposure to childhood neglect were only associated with increased sBDNF levels in subjects with the CC genotype, but not in subjects with other genotypes. Our findings suggest that genetic variants in NR3C2 gene may partially explain plastic brain vulnerability to traumatic events. Further studies are needed to investigate the moderating effects of NR3C2 gene in more specific markers of alteration in brain function.

The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function.

BACKGROUND: Individuals with panic disorder (PD) exhibit a hypersensitivity to inhaled carbon dioxide, possibly reflecting a lowered threshold for sensing signals of suffocation. Animal studies have shown that carbon dioxide-mediated fear behavior depends on chemosensing of acidosis in the amygdala via the acid-sensing ion channel ASIC1a. We examined whether the human ortholog of the ASIC1a gene, ACCN2, is associated with the presence of PD and with amygdala structure and function. METHODS: We conducted a case-control analysis (n = 414 PD cases and 846 healthy controls) of ACCN2 single nucleotide polymorphisms and PD. We then tested whether variants showing significant association with PD are also associated with amygdala volume (n = 1048) or task-evoked reactivity to emotional stimuli (n = 103) in healthy individuals. RESULTS: Two single nucleotide polymorphisms at the ACCN2 locus showed evidence of association with PD: rs685012 (odds ratio = 1.32, gene-wise corrected p = .011) and rs10875995 (odds ratio = 1.26, gene-wise corrected p = .046). The association appeared to be stronger when early-onset (age ≤ 20 years) PD cases and when PD cases with prominent respiratory symptoms were compared with controls. The PD risk allele at rs10875995 was associated with increased amygdala volume (p = .035) as well as task-evoked amygdala reactivity to fearful and angry faces (p = .0048). CONCLUSIONS: Genetic variation at ACCN2 appears to be associated with PD and with amygdala phenotypes that have been linked to proneness to anxiety. These results support the possibility that modulation of acid-sensing ion channels may have therapeutic potential for PD.