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1.
Artigo em Alemão | MEDLINE | ID: mdl-33246345

RESUMO

Our study compared the psychometric properties of two broad scope symptom questionnaires, the Brief Symptom Inventory [7] and the ICD-10 Symptom Rating Scale [8], in a naturalistic data set of 507 patients in outpatient psychotherapeutic treatment. Reliability of total scores and subscale scores were estimated via internal consistency coefficients Cronbach's α and McDonald's ω. Measurement precision was operationalized via the uncertainty interval. Validity of the total scores as measures of symptom load was operationalized via convergence analysis with measures similar and dissimilar to that concept. Validity of the internal structure of each scale was operationalized via confirmatory factor analysis of multiple models established in literature. Reliability and measurement precision were comparable for the two questionnaires. The convergent and discriminant validity of both instruments appear to be similarly sufficient. The ISR clearly showed good factorial validity, whereas the BSI was found to have poor factorial validity. Due to its uncertain factorial structure, interpretation of the BSI subscales is not advised. In sum, the ISR and BSI have comparable reliability and measurement precision, but ISR has superior validity and better time efficiency and therefore can be considered a valid alternative to the BSI.

2.
J Neural Transm (Vienna) ; 127(11): 1527-1537, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32468273

RESUMO

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

3.
Behav Res Ther ; 124: 103530, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862473

RESUMO

The availability of large-scale datasets and sophisticated machine learning tools enables developing models that predict treatment outcomes for individual patients. However, few studies used routinely available sociodemographic and clinical data for this task, and many previous investigations used highly selected samples. This study aimed to investigate cognitive behavioral therapy (CBT) outcomes in a large, naturalistic and longitudinal dataset. Routine data from a university-based outpatient center with n = 2.147 patients was analyzed. Only baseline data including sociodemographics, symptom measures and functional impairment ratings was used for prediction. Different competing classification and regression models were compared to each other; the best models were then applied to previously unseen validation data. Applied on the validation set, the best performing classification model for remission achieved a balanced accuracy of 59% (p < 0.001) and the best performing regression model for dimensional change achieved r = 0.27 (p < 0.001). Age, sex, functional impairment, symptom severity, and axis II comorbidity were among the most important features. Predictor performances significantly exceeded chance level but were far from clinical utility. Neither applying more sophisticated approaches nor restricting the sample to homogeneous subgroups resulted in considerable performance gains. Adding hypotheses-based, more specific clinical constructs and deep (e.g. neurobiological) to digital phenotypes may increase prediction performance.

4.
Mol Psychiatry ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31712720

RESUMO

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

5.
Eur Neuropsychopharmacol ; 29(10): 1138-1151, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31444036

RESUMO

The gene coding for glycine receptor ß subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk¼) in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.


Assuntos
Agorafobia/fisiopatologia , Alelos , Encéfalo/fisiopatologia , Medo/fisiologia , Transtorno de Pânico/fisiopatologia , Receptores da Glicina/genética , Agorafobia/complicações , Agorafobia/genética , Agorafobia/terapia , Aprendizagem da Esquiva/fisiologia , Condicionamento Psicológico/fisiologia , Neuroimagem Funcional , Genótipo , Humanos , Terapia Implosiva , Imagem por Ressonância Magnética , Transtorno de Pânico/complicações , Transtorno de Pânico/genética , Transtorno de Pânico/terapia , Polimorfismo de Nucleotídeo Único/genética
6.
Transl Psychiatry ; 9(1): 150, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123309

RESUMO

Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (rg ≈ 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We estimated the variance in therapy outcomes that could be explained by common genetic variants (h2SNP) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h2SNP could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.


Assuntos
Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Terapia Cognitivo-Comportamental/estatística & dados numéricos , Transtorno Depressivo Maior/genética , Transtorno Depressivo Maior/terapia , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Criança , Humanos
7.
J Anxiety Disord ; 64: 16-23, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30875662

RESUMO

Patients with anxiety disorders have a lower heart rate variability (HRV) than healthy controls. Low HRV is associated with cardiovascular disease and dysfunction of the autonomic nervous system (ANS). The aim of the present study was to investigate if HRV in patients with agoraphobia with or without panic disorder can be influenced by cognitive behavioral therapy (CBT). 73 patients with agoraphobia with or without panic disorder were included in the study. Heart rate (HR) and HRV were recorded at rest before and after CBT and during in-vivo exposure. No changes in HR and HRV were observed throughout therapy. During in-vivo exposure HRV increased significantly and HR exhibited a tendency to decrease. Despite clinical improvement of anxiety symptoms, ANS activity at rest did not seem to be influenced by CBT. However, during in-vivo exposure, HRV changed significantly, indicating a higher parasympathetic activity at the end of exposure.


Assuntos
Agorafobia/complicações , Agorafobia/fisiopatologia , Terapia Cognitivo-Comportamental , Frequência Cardíaca , Transtorno de Pânico/complicações , Adulto , Agorafobia/psicologia , Agorafobia/terapia , Sistema Nervoso Autônomo/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/psicologia
8.
Transl Psychiatry ; 9(1): 75, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718541

RESUMO

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10-7), particularly in the female subsample (p = 9.8 × 10-9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10-4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.


Assuntos
Agorafobia , Aprendizagem da Esquiva/fisiologia , Cérebro/fisiopatologia , Terapia Cognitivo-Comportamental , Medo/fisiologia , Receptores de Orexina/genética , Avaliação de Resultados em Cuidados de Saúde , Transtorno de Pânico , Adulto , Agorafobia/genética , Agorafobia/fisiopatologia , Agorafobia/terapia , Estudos de Casos e Controles , Cérebro/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/genética , Transtorno de Pânico/fisiopatologia , Transtorno de Pânico/terapia , Fenótipo , Adulto Jovem
9.
Psychoneuroendocrinology ; 102: 212-215, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30583245

RESUMO

Physiological mechanisms of an anti-depressive effect of physical exercise in major depressive disorder (MDD) seem to involve alterations in brain-derived neurotrophic factor (BDNF) level. However, previous studies which investigated this effect in a single bout of exercise, did not control for confounding peripheral factors that contribute to BDNF-alterations. Therefore, the underlying cause of exercise-induced BDNF-changes remains unclear. The current study aims to investigate serum BDNF (sBDNF)-changes due to a single-bout of graded aerobic exercise in a group of 30 outpatients with MDD, suggesting a more precise analysis method by taking plasma volume shift and number of platelets into account. Results show that exercise-induced increases in sBDNF remain significant (p < .001) when adjusting for plasma volume shift and controlling for number of platelets. The interaction of sBDNF change and number of platelets was also significant (p = .001) indicating larger sBDNF-increase in participants with smaller number of platelets. Thus, findings of this study suggest an involvement of peripheral as well as additional - possibly brain-derived - mechanisms explaining exercise-related BDNF release in MDD. For future studies in the field of exercise-related BDNF research, the importance of controlling for peripheral parameters is emphasized.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/análise , Transtorno Depressivo Maior/metabolismo , Exercício Físico/fisiologia , Adulto , Fator Neurotrófico Derivado do Encéfalo/sangue , Transtorno Depressivo Maior/sangue , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso/fisiologia
10.
World J Psychiatry ; 6(3): 351-7, 2016 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-27679775

RESUMO

AIM: To examine the associations of test anxiety (TA) in written vs oral exam situations with social anxiety (SA). METHODS: A convenience sample of 204 students was recruited at the Technische Universität Dresden (TU Dresden, Germany) and contacted via e-mail asking to complete a cross-sectional online survey based on established questionnaires. The study protocol was approved by the ethics committee of the TU Dresden. Full data of n = 96 students were available for dependent t-tests and correlation analyses on the associations of SA and TA respectively with trigger events, cognitions, safety behaviors, physical symptoms and depersonalization. Analyses were run using SPSS. RESULTS: Levels of TA were higher for fear in oral exams than for fear in written exams (M = 48.1, SD = 11.5 vs M = 43.7, SD = 10.1 P < 0.001). Oral TA and SA were positively correlated (Spearman's r = 0.343, P < 0.001; Pearson's r = 0.38, P < 0.001) contrasting written TA and SA (Spearman's r = 0.17, P > 0.05; Pearson's r = 0.223, P > 0.05). Compared to written TA, trigger events were more often reported for oral TA (18.2% vs 30.3%, P = 0.007); which was also accompanied more often by test-anxious cognitions (7.9% vs 8.5%, P = 0.001), safety behavior (8.9% vs 10.3%, P < 0.001) and physical symptoms (for all, P < 0.001). CONCLUSION: Written, but not oral TA emerged being unrelated to SA and may rather not be considered as a typical facet of SA disorder.

11.
Eur Neuropsychopharmacol ; 26(3): 431-44, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26837851

RESUMO

INTRODUCTION: Cognitive behavioural therapy (CBT) and pharmacological treatment with selective serotonin or serotonin-noradrenalin reuptake inhibitors (SSRI/SSNRI) are regarded as efficacious treatments for panic disorder with agoraphobia (PD/AG). However, little is known about treatment-specific effects on symptoms and neurofunctional correlates. EXPERIMENTAL PROCEDURES: We used a comparative design with PD/AG patients receiving either two types of CBT (therapist-guided (n=29) or non-guided exposure (n=22)) or pharmacological treatment (SSRI/SSNRI; n=28) as well as a wait-list control group (WL; n=15) to investigate differential treatment effects in general aspects of fear and depression (Hamilton Anxiety Rating Scale HAM-A and Beck Depression Inventory BDI), disorder-specific symptoms (Mobility Inventory MI, Panic and Agoraphobia Scale subscale panic attacks PAS-panic, Anxiety Sensitivity Index ASI, rating of agoraphobic stimuli) and neurofunctional substrates during symptom provocation (Westphal-Paradigm) using functional magnetic resonance imaging (fMRI). Comparisons of neural activation patterns also included healthy controls (n=29). RESULTS: Both treatments led to a significantly greater reduction in panic attacks, depression and general anxiety than the WL group. The CBT groups, in particular, the therapist-guided arm, had a significantly greater decrease in avoidance, fear of phobic situations and anxiety symptoms and reduction in bilateral amygdala activation while the processing of agoraphobia-related pictures compared to the SSRI/SSNRI and WL groups. DISCUSSION: This study demonstrates that therapist-guided CBT leads to a more pronounced short-term impact on agoraphobic psychopathology and supports the assumption of the amygdala as a central structure in a complex fear processing system as well as the amygdala's involvement in the fear system's sensitivity to treatment.


Assuntos
Agorafobia/tratamento farmacológico , Agorafobia/reabilitação , Encéfalo/fisiologia , Terapia Cognitivo-Comportamental , Transtorno de Pânico/tratamento farmacológico , Transtorno de Pânico/reabilitação , Inibidores de Captação de Serotonina/uso terapêutico , Agorafobia/complicações , Agorafobia/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Medo/psicologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Oxigênio/sangue , Transtorno de Pânico/complicações , Transtorno de Pânico/diagnóstico por imagem , Inventário de Personalidade , Escalas de Graduação Psiquiátrica , Autorrelato , Estatística como Assunto , Resultado do Tratamento
12.
Psychiatry Res ; 230(2): 668-75, 2015 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-26545614

RESUMO

Exposure therapy is considered an effective treatment strategy for phobic anxiety, however, it is rarely applied in clinical practice. The under-usage might be due to various factors of which heightened stress levels not only in patients but also in therapists are presumed to be of particular relevance. The present study aimed to investigate whether different forms of exposure might lead to varying physiological and psychological stress responses in therapists and phobic patients. 25 patients with specific phobia underwent individual cognitive behavioural therapy, performed by 25 psychotherapist trainees, applying exposure sessions in graduated form or the flooding technique. Patients and therapists provided subjective evaluations of stress and five saliva samples for analysis of salivary cortisol and alpha-amylase either during two graduated exposure sessions or during one flooding session, while a regular therapy session served as control condition. Therapists displayed heightened salivary alpha-amylase release during exposure of the flooding, but not the graduated, type. Patients showed elevated salivary cortisol during flooding exposure numerically, however, not on a statistically significant level. Therapists reported more pronounced subjective stress during flooding compared to graduated exposure. Elevated stress levels should be addressed in clinical training in order to improve application of exposure in routine practice.


Assuntos
Terapia Implosiva/métodos , Transtornos Fóbicos/fisiopatologia , Estresse Psicológico/fisiopatologia , Adulto , Ansiedade/fisiopatologia , Ansiedade/psicologia , Terapia Cognitivo-Comportamental/métodos , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Transtornos Fóbicos/psicologia , Transtornos Fóbicos/terapia , Psicoterapia , Saliva/química , alfa-Amilases Salivares/metabolismo , Estresse Psicológico/psicologia
13.
Am J Med Genet B Neuropsychiatr Genet ; 168B(3): 211-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25740197

RESUMO

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.


Assuntos
Transtornos de Ansiedade/etiologia , Biomarcadores/análise , Predisposição Genética para Doença , Transtorno de Pânico/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas RGS/genética , Adulto , Transtornos de Ansiedade/psicologia , Mapeamento Encefálico , Estudos de Casos e Controles , Emoções/fisiologia , Feminino , Seguimentos , Genótipo , Haplótipos , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Transtorno de Pânico/complicações , Transtorno de Pânico/psicologia , Personalidade , Fenótipo , Projetos Piloto , Prognóstico , Testes Psicológicos
14.
J Anxiety Disord ; 28(8): 836-44, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25445073

RESUMO

The potentially detrimental effects of safety behaviors during exposure therapy are still subject to debate. Empirical findings are inconsistent, and few studies have investigated effects of idiosyncratic safety behavior manifestations during exposure or in everyday life. These limitations might be due to a lack of appropriate measures that address individual safety behaviors. We examined psychometric properties and predictive value of the Texas Safety Maneuver Scale (TSMS), a questionnaire specifically targeting safety behaviors in panic disorder and agoraphobia. Effects of safety behavior use, both during everyday life and during therapy, were examined using data from a multicenter RCT of N=268 patients that aimed at evaluating efficacy and mechanisms of action of two variants of an exposure-based therapy. The TSMS total score demonstrated good internal consistency (α=0.89), and it showed significant correlations with selected measures of baseline anxiety and impairment. The proposed factor structure could not be replicated. Frequent safety behavior use at baseline was associated with actual safety behavior during exposure exercises. Pronounced in-situ safety behavior, but not baseline safety behavior was associated to detrimental treatment outcome. The results underline the relevance of a rigorous safety behavior assessment in therapy. The actual relationship between safety behavior use and treatment outcome is yet to determine.


Assuntos
Agorafobia/terapia , Terapia Implosiva/métodos , Transtorno de Pânico/terapia , Segurança , Inquéritos e Questionários , Atividades Cotidianas , Adulto , Agorafobia/psicologia , Ansiedade/psicologia , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Análise Discriminante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtorno de Pânico/psicologia , Psicometria , Reprodutibilidade dos Testes , Resultado do Tratamento
15.
Psychoneuroendocrinology ; 49: 280-9, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25127086

RESUMO

In cognitive behavioural therapy of phobic anxiety, in vivo exposure is considered as an effective treatment strategy. Apparently, it involves the experience of stress and anxiety in patients. Given the therapist's role during exposure sessions, it is conceivable that the performance is also accompanied with the experience of stress in therapists, especially when unversed in conducting psychotherapy. Studies confirmed that cognitive behavioural therapists tend to avoid therapist-guided in vivo exposure. The objective of this study was the simultaneous investigation of therapist's and patient's stress response during in vivo exposure. Therefore, 23 agoraphobic patients and their 23 treating therapists in training provided five saliva samples during an in vivo exposure and five samples during an ordinary therapy session. Before and during exposure session, subjective evaluations of stress and anxiety were assessed. Results suggested that therapists reported similar levels of perceived stress as patients before exposure. Both groups displayed significantly elevated salivary cortisol (sC) levels during exposure compared to the control session and a trend for alterations in salivary alpha-amylase (sAA) activity was found. Therapists reached peak concentrations of sC before start of the intervention followed by a decline during exposure, while patients displayed peak levels of cortisol secretion after 60 min of exposure. In vivo exposure seems to be a demanding intervention not only for the patient, but also for therapists in training. However, it was also demonstrated that physiological and subjective stress rather decrease during the intervention and that both groups rated exposure to be substantially successful. Based on the presented results, another potential factor contributing to the under-usage of exposure treatment is conceivable and needs to be addressed in future research.


Assuntos
Agorafobia/metabolismo , Hidrocortisona/metabolismo , Terapia Implosiva , Psicoterapia , Saliva/metabolismo , alfa-Amilases Salivares/metabolismo , Estresse Psicológico/metabolismo , Adulto , Agorafobia/complicações , Ansiedade/complicações , Ansiedade/metabolismo , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Percepção/fisiologia , Projetos Piloto , Saliva/enzimologia , Estresse Psicológico/complicações , Adulto Jovem
16.
Depress Anxiety ; 31(10): 843-50, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24390875

RESUMO

BACKGROUND: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders. METHODS: We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115). RESULTS: Case-control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female-specific effect of the associations of both SNPs. CONCLUSIONS: These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender-specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results.


Assuntos
20-Hidroxiesteroide Desidrogenases/genética , Ansiedade/genética , Transtorno de Pânico/genética , Pregnanolona/metabolismo , Progesterona/metabolismo , 3-Hidroxiesteroide Desidrogenases/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Adulto , Membro C3 da Família 1 de alfa-Ceto Redutase , Ansiedade/metabolismo , Ansiedade/psicologia , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Hidroxiprostaglandina Desidrogenases/genética , Hidroxiesteroide Desidrogenases/genética , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Transtorno de Pânico/metabolismo , Transtorno de Pânico/psicologia , Polimorfismo de Nucleotídeo Único , Receptores de GABA/genética , Fatores Sexuais
17.
J Clin Psychol ; 69(6): 616-29, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23504641

RESUMO

OBJECTIVES: Although homework assignments are an integral component of cognitive-behavioral therapy (CBT) and relate to positive therapy outcomes, it is unclear whether specific homework types and their completion have specific effects on outcome. METHOD: Data from N = 292 patients (75% female, mean age 36 years) with panic disorder and agoraphobia and treated with standardized CBT were analyzed with homework compliance quality and quantity for different types of homework serving as predictors for different outcome variables. RESULTS: Quality ratings of homework completion were stronger outcome predictors than quantitative compliance ratings. Exposure homework was a better outcome predictor than homework relating to psychoeducation and self-monitoring. CONCLUSION: Different aspects of homework compliance and specific homework types might differentially relate to CBT outcome.


Assuntos
Agorafobia/terapia , Terapia Cognitivo-Comportamental/métodos , Comportamento Cooperativo , Avaliação de Resultados em Cuidados de Saúde , Transtorno de Pânico/terapia , Cooperação do Paciente , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
18.
PLoS One ; 7(5): e37651, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22662185

RESUMO

BACKGROUND: Panic disorder is common (5% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. METHODOLOGY/PRINCIPAL FINDINGS: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype×gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype×gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. CONCLUSIONS/SIGNIFICANCE: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.


Assuntos
Glutamato Descarboxilase/genética , Transtorno de Pânico/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Sexuais
19.
Biol Psychiatry ; 72(6): 512-20, 2012 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-22621998

RESUMO

BACKGROUND: The learning perspective of panic disorder distinguishes between acute panic and anxious apprehension as distinct emotional states. Following animal models, these clinical entities reflect different stages of defensive reactivity depending upon the imminence of interoceptive or exteroceptive threat cues. The current study tested this model by investigating the dynamics of defensive reactivity in a large group of patients with panic disorder and agoraphobia (PD/AG). METHODS: Three hundred forty-five PD/AG patients participated in a standardized behavioral avoidance test (being entrapped in a small, dark chamber for 10 minutes). Defense reactivity was assessed measuring avoidance and escape behavior, self-reports of anxiety and panic symptoms, autonomic arousal (heart rate and skin conductance), and potentiation of the startle reflex before and during exposure of the behavioral avoidance test. RESULTS: Panic disorder and agoraphobia patients differed substantially in their defensive reactivity. While 31.6% of the patients showed strong anxious apprehension during this task (as indexed by increased reports of anxiety, elevated physiological arousal, and startle potentiation), 20.9% of the patients escaped from the test chamber. Active escape was initiated at the peak of the autonomic surge accompanied by an inhibition of the startle response as predicted by the animal model. These physiological responses resembled the pattern observed during the 34 reported panic attacks. CONCLUSIONS: We found evidence that defensive reactivity in PD/AG patients is dynamically organized ranging from anxious apprehension to panic with increasing proximity of interoceptive threat. These data support the learning perspective of panic disorder.


Assuntos
Agorafobia/fisiopatologia , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Mecanismos de Defesa , Transtorno de Pânico/fisiopatologia , Transtornos Fóbicos/fisiopatologia , Adulto , Agorafobia/psicologia , Análise de Variância , Ansiedade/psicologia , Nível de Alerta/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Transtorno de Pânico/psicologia , Testes Psicológicos , Reflexo de Sobressalto/fisiologia
20.
J Anxiety Disord ; 26(5): 608-16, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22445318

RESUMO

OBJECTIVES: For characterizing the association between parenting and offspring social phobia (SP), contrasting maternal vs. paternal contributions, putative predictors of unfavorable parenting behaviors and its specificity for SP are warranted to delineate targeted prevention and intervention strategies. METHODS: A population-based sample of 1053 adolescents was followed-up using the M-CIDI. Parenting was assessed via questionnaire in offspring passing the high risk period for SP-onset. Natal complications and childhood serious health problems as assessed by maternal reports were hypothesized to relate to unfavorable parenting. RESULTS: The pattern of maternal overprotection, paternal rejection and lower emotional warmth was associated with SP, but not with other offspring anxiety disorders. Natal complications were related to overprotection and lower emotional warmth; trend-level associations emerged for serious health problems and unfavorable parenting. CONCLUSIONS: Paternal behavior appears particularly relevant for SP. The pattern of maternal overprotection, paternal rejection and lower emotional warmth was observed in SP only, suggesting that its detailed assessment provides a promising opportunity for targeted prevention and intervention in SP.


Assuntos
Relações Pais-Filho , Poder Familiar/psicologia , Transtornos Fóbicos/etiologia , Adolescente , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pais/psicologia , Transtornos Fóbicos/diagnóstico , Transtornos Fóbicos/psicologia , Escalas de Graduação Psiquiátrica , Inquéritos e Questionários , Adulto Jovem
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