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1.
Sci Rep ; 11(1): 7960, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846417

RESUMO

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense.Trial Registration Number: ISRCTN80046034.

2.
Transl Psychiatry ; 11(1): 177, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33731674

RESUMO

Panic disorder (PD) is characterized by a dysfunctional defensive responding to panic-related body symptoms that is assumed to contribute to the persistence of panic symptomatology. The present study aimed at examining whether this dysfunctional defensive reactivity to panic-related body symptoms would no longer be present following successful cognitive behavior therapy (CBT) but would persist when patients show insufficient symptom improvement. Therefore, in the present study, effects of CBT on reported symptoms and defensive response mobilization during interoceptive challenge were investigated using hyperventilation as a respiratory symptom provocation procedure. Changes in defensive mobilization to body symptoms in the course of CBT were investigated in patients with a primary diagnosis of PD with or without agoraphobia by applying a highly standardized hyperventilation task prior to and after a manual-based CBT (n = 38) or a waiting period (wait-list controls: n = 20). Defensive activation was indexed by the potentiation of the amygdala-dependent startle eyeblink response. All patients showed a pronounced defensive response mobilization to body symptoms at baseline. After treatment, no startle reflex potentiation was found in those patients who showed a clinically significant improvement. However, wait-list controls and treatment non-responders continued to show increased defensive responses to actually innocuous body symptoms after the treatment/waiting period. The present results indicate that the elimination of defensive reactivity to actually innocuous body symptoms might be a neurobiological correlate and indicator of successful CBT in patients with PD, which may help to monitor and optimize CBT outcomes.

3.
Psychiatry Res ; 293: 113462, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32987222

RESUMO

The COVID-19 pandemic is suggested to have a negative impact on mental health. To prevent the spread of Sars-CoV-2, governments worldwide have implemented different forms of public health measures ranging from physical distancing recommendations to stay-at-home orders, which have disrupted individuals' everyday life tremendously. However, evidence on the associations of the COVID-19 pandemic and public health measures with mental health are limited so far. In this study, we investigated the role of sociodemographic and COVID-19 related factors for immediate mental health consequences in a nationwide community sample of adults from Germany (N = 4335). Specifically, we examined the effects of different forms and levels of restriction resulting from public health measures (e.g. quarantine, stay-at-home order) on anxiety and depression symptomatology, health anxiety, loneliness, the occurrence of fearful spells, psychosocial distress and life-satisfaction. We found that higher restrictions due to lockdown measures, a greater reduction of social contacts and greater perceived changes in life were associated with higher mental health impairments. Importantly, a subjectively assumed but not an officially announced stay-at-home order was associated with poorer mental health. Our findings underscore the importance of adequate risk communication and targeted mental health recommendations especially for vulnerable groups during these challenging times.


Assuntos
Ansiedade/psicologia , Betacoronavirus , Infecções por Coronavirus/psicologia , Depressão/psicologia , Pneumonia Viral/psicologia , Quarentena/psicologia , Estresse Psicológico/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/epidemiologia , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Quarentena/métodos , Estresse Psicológico/epidemiologia , Adulto Jovem
5.
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.

6.
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.

7.
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
8.
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
9.
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
10.
J Affect Disord ; 245: 905-911, 2019 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699875

RESUMO

BACKGROUND: Findings on associations of androgens and sex hormone-binding globulin (SHBG) with anxiety and depressive disorders in the general population remain inconclusive. METHODS: We used data of n = 993 men and n = 980 women from the Study of Health in Pomerania (SHIP, a prospective-longitudinal general population study from northeastern Germany). Immunoassay-measured serum concentrations of total testosterone, androstenedione and SHBG were assessed when participants were aged 20-80. 12-month, lifetime and incident DSM-IV anxiety and depressive disorders were assessed with the DIA-X/M-CIDI at 10-year follow-up, when participants were aged 29-89. Logistic regressions were adjusted for age, smoking, alcohol consumption, physical activity, waist circumference, hypertension and oral contraceptive use (women only) at baseline and follow-up interval. RESULTS: In men and women, androgens and SHBG were not associated significantly with incident anxiety and depressive disorders. In men, higher total testosterone predicted any 12-month (OR = 1.46) and lifetime (OR = 1.34) anxiety disorder, lifetime social phobia (OR = 2.15), and 12-month (OR = 1.48) and lifetime (OR = 1.39) specific phobia, but neither 12-month nor lifetime depression. Moreover, androstenedione in men interacted with age in predicting lifetime anxiety disorders (OR = 0.98): Higher androstenedione more strongly predicted lifetime anxiety in younger vs. older men. These findings, however, did not survive correction for multiple testing. In women, androgens and SHBG were not associated significantly with 12-month and lifetime anxiety and depressive disorders. LIMITATIONS: The follow-up period was relatively long and other factors might have affected the examined associations. CONCLUSIONS: Higher serum total testosterone in men and androstenedione in younger men may relate to an increased risk of anxiety disorders.


Assuntos
Androgênios/sangue , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo/sangue , Transtorno Depressivo/epidemiologia , Globulina de Ligação a Hormônio Sexual/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/sangue , Envelhecimento/psicologia , Androstenodiona/sangue , Transtornos de Ansiedade/psicologia , Transtorno Depressivo/psicologia , Feminino , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fobia Social/sangue , Fobia Social/psicologia , Estudos Prospectivos , Caracteres Sexuais , Testosterona/sangue , Adulto Jovem
11.
Behav Res Ther ; 112: 63-67, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502722

RESUMO

Excessive anxiety and avoidance during provocation of body symptoms are core features of anxiety-related disorders and might contribute to the development and maintenance of these disorders. Previous studies examined psychological (anxiety sensitivity, fear of suffocation and trait anxiety) and biobehavioral (breath-holding time) predictors of reported anxiety during symptom provocation. However, the role of these predictors on avoidance of feared body symptoms remains unclear. Therefore, the present work aimed at investigating the main and interactive effects of psychological and biobehavioral variables in predicting avoidance during provocation of dyspnea that successively increased in severity. 28 of 69 participants prematurely terminated the provocation sequence, thus preventing further progression of symptom provocation. Logistic regressions revealed that higher anxiety sensitivity and lower breath-holding time were significantly associated with avoidance during exposure. Suffocation fear and trait anxiety were not related to avoidance. Moreover, there was a significant interaction between breath-holding time and anxiety sensitivity in predicting avoidance. Participants with a lower breath-holding time showed more avoidance behavior when reporting high as compared to low anxiety sensitivity. The data suggest that anxiety sensitivity and breath-holding time increase the risk to show avoidance and thus might contribute to the development and maintenance of anxiety-related disorders.


Assuntos
Ansiedade/psicologia , Aprendizagem da Esquiva , Suspensão da Respiração , Dispneia/psicologia , Personalidade , Adulto , Asfixia , Medo/psicologia , Feminino , Humanos , Modelos Logísticos , Masculino , Adulto Jovem
12.
Behav Modif ; 43(4): 467-489, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-29690770

RESUMO

Interoceptive exposure is one component in cognitive behavioral therapy of panic disorder. The present investigation addressed changes in defensive mobilization during repeated interoceptive exposure using a standardized hyperventilation procedure. 26 high and 22 low anxiety sensitive persons (ASI, Peterson & Reiss, 1992) went through two guided hyperventilation and normoventilation procedures, spaced one week apart. Breathing parameters, startle response magnitudes and symptom reports were measured. All participants successfully adhered to the guided breathing procedures. Both groups comparably reported more symptoms during hyperventilation than normoventilation in both sessions. Only high-AS participants displayed potentiated startle magnitudes after the first hyperventilation vs. normoventilation. One week later, when the hyperventilation exercise was repeated, this potentiation was no longer present. Thus, high and low-AS groups no longer differed in their defensive mobilization to symptom provocation. Furthermore, the number of reported baseline symptoms also decreased from session one to session two in the high-AS group. While high-AS reported increased baseline anxiety symptoms in session 1, groups did not differ in session 2. Results indicate a reduction of defensive mobilization during repeated interoceptive exposure.


Assuntos
Ansiedade/psicologia , Interocepção , Ansiedade/diagnóstico , Feminino , Humanos , Hiperventilação , Masculino , Escalas de Graduação Psiquiátrica , Reflexo de Sobressalto , Respiração , Adulto Jovem
13.
Pain Rep ; 3(Suppl 1): e680, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30324172

RESUMO

Introduction: Fear of pain seems to be a key factor in the development and maintenance of chronic pain and pain-related disability. Interoceptive fear conditioning is assumed to constitute an important mechanism in the origins and maintenance of fear of pain. If conditioned stimuli such as internal bodily sensations are repeatedly paired with pain (unconditioned stimulus), they in turn elicit a conditioned fear response, including defence mobilization such as startle modulation and changes in heart rate and electrodermal activity. Research into emotional imagery suggests that defensive responses can also be elicited through imagery of fear scripts. Objectives: We present 2 novel paradigms adapted from research on anxiety disorders, which allow to test, if perceived or imagined sensations locally proximal to the main pain location trigger heightened defence response mobilization in adolescents with chronic headaches and abdominal pain. Methods: The provocation paradigm includes the anticipation and provocation of locally proximal and locally distal interoceptive sensations through disorder-specific muscle tensing tasks (tightening the neck or the abdominal muscles). The imagery paradigm includes 3 imagery scripts (standard neutral, standard fear, and disorder-specific). Startle probes are presented in both paradigms. Defence response mobilization is assessed using psychophysiological measures (startle response modulation, skin conductance level, and heart rate), as well as self-reported measures of fear. Perspective: The paradigms will give insight into the defence response of adolescents with chronic pain, when confronted with or imagining interoceptive sensations. Results may inform the improvement of clinical interventions aimed to decrease fear of bodily sensations such as interoceptive exposure or interoceptive imagery exposure.

14.
Depress Anxiety ; 35(11): 1104-1113, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30107643

RESUMO

BACKGROUND: It remains unresolved whether childhood adversities interact with genetic variation in regulator of G-protein signaling 2 (RGS2) rs4606 in predicting various anxiety and depressive disorders and whether diagnostic specificity exists in these interactions. METHODS: The genotype of RGS2 rs4606 was determined for N = 2,263 adults with European ancestry from the Study of Health in Pomerania. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were assessed with the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ, when participants were aged 29-89). RESULTS: Logistic regressions adjusted for sex and age revealed that rs4606 interacted with total childhood adversity in predicting each diagnostic outcome except for panic disorder and generalized anxiety disorder, uncorrected and corrected for multiple testing (odds ratio [OR] = 1.06-1.16). That is, carriers of the GG (vs. CC/CG) genotype were at decreased risk for anxiety and/or depression in the presence of low, but at increased risk in the presence of high total childhood adversity. Respective gene-environment (G × E) interactions were found for (a) comorbid anxiety and depressive disorders (OR = 1.13), but neither pure anxiety nor pure depressive disorders and (b) pure/temporally primary anxiety disorders (OR = 1.07), but not pure/temporally primary depressive disorders. The G × E interaction remained associated with depressive disorders after introducing pure/temporally primary anxiety disorders as additional predictor (OR = 1.09). CONCLUSIONS: rs4606 alters the risk of developing a range of anxiety but also depressive disorders after childhood adversities. A complex risk pattern of genotype, environmental factors, and preexisting anxiety contributes to subsequent depression development.


Assuntos
Adultos Sobreviventes de Eventos Adversos na Infância , Transtornos de Ansiedade , Transtorno Depressivo , Interação Gene-Ambiente , Proteínas RGS/genética , Adulto , Adultos Sobreviventes de Eventos Adversos na Infância/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/genética , Transtorno Depressivo/epidemiologia , Transtorno Depressivo/etiologia , Transtorno Depressivo/genética , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
Artigo em Inglês | MEDLINE | ID: mdl-29884283

RESUMO

BACKGROUND: Excessive fear and anxiety are core features of anxiety disorders. Defensive response mobilization varies dynamically with threat proximity. METHODS: We analyzed defensive responses in 48 healthy students to an approaching external, predator-like threat (an electric shock resembling a predator attack) versus an approaching threat from inside the body (feeling of dyspnea as evoked by forced breath-holding). Threats either were inevitable or could be avoided by button press. RESULTS: Autonomic changes (heart rate, skin conductance), defensive reflex priming (startle eyeblink response), respiratory responses, and event-related potentials were assessed. Regardless of its source, when an approaching threat was inevitable, a defensive pattern emerged characterized by an increase in skin conductance, a potentiation of the startle reflex, and bradycardia. Minute ventilation increased only with approaching dyspnea. In preparation for active avoidance of either threat, startle magnitudes were inhibited and probe-elicited P3 wave amplitudes were reduced. Moreover, generation of avoidant action resulted in heart rate acceleration. CONCLUSIONS: This study demonstrates common and specific defensive activation patterns for approaching external and respiratory threats. The specific modulation in respiration in response to an inevitable respiratory threat may have important implications for our understanding of the etiology of anxiety disorders, especially panic disorder.


Assuntos
Transtornos de Ansiedade/fisiopatologia , Ansiedade/fisiopatologia , Medo/psicologia , Reflexo de Sobressalto/fisiologia , Adolescente , Adulto , Emoções/fisiologia , Medo/fisiologia , Feminino , Humanos , Masculino , Transtorno de Pânico/fisiopatologia , Adulto Jovem
17.
J Affect Disord ; 234: 290-296, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29574383

RESUMO

BACKGROUND: The single nucleotide polymorphism rs4680 of the catechol-O-methyltransferase (COMT) gene has been implicated to be involved in the etiopathogenesis of panic. However, it remains unresolved whether rs4680 modifies the risk-association between early life stress and subsequent development of panic pathology. METHODS: The genotype of rs4680 was determined for n = 2242 adults with European ancestry from the Study of Health in Pomerania (SHIP, a regional longitudinal cohort study from northeastern Germany). Lifetime fearful spells, panic attacks and panic disorder were assessed according to DSM-IV in 2007-2010 (when participants were aged 29-89) using the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ). RESULTS: Logistic regressions with interaction terms (adjusted for sex and age) revealed that rs4680 interacted with total childhood adversity, emotional abuse and physical abuse in predicting panic disorder: Respective childhood adversities predicted panic disorder in carriers of the Val/Met or Met/Met genotype, but not Val/Val genotype. Moreover, a 3-way interaction was found between rs4680, emotional abuse and sex in predicting panic attacks: Emotional abuse predicted panic attacks among male carriers of the Val/Val genotype and female carriers of the Val/Met or Met/Met genotype, but not among male carriers of the Val/Met or Met/Met genotype or female carriers of the Val/Val genotype. LIMITATIONS: Genotype data were derived by imputation. Childhood adversities and panic were assessed retrospectively. CONCLUSIONS: Especially (female) carriers of the Val/Met or Met/Met genotype of rs4680 might profit from targeted early interventions to prevent the onset of panic after childhood adversities.


Assuntos
Catecol O-Metiltransferase/genética , Maus-Tratos Infantis/psicologia , Predisposição Genética para Doença , Transtorno de Pânico/genética , Adulto , Criança , Medo , Feminino , Genótipo , Heterozigoto , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Fatores Sexuais , Estresse Psicológico
18.
Int J Psychophysiol ; 124: 33-42, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29330006

RESUMO

Interoceptive threats play a crucial role in the etiology of panic disorder (PD). While body sensations may become conditioned stimuli (CS) when paired with such interoceptive threats (cue conditioning), the environment in which such interoceptive threats occur may also be learned as a predictor of threat (context conditioning). Suffocation fear (SF) might facilitate these associative learning processes if threats of suffocation become relevant as unconditioned stimuli (US). To investigate whether SF affects associative learning during such respiratory threat, we used mild dyspnea as CS that predicted the occurrence of strong dyspnea (US) in one context (predictable), was not related to the occurrence of the US in another context (unpredictable) or was presented in a different context (safe) in which no US was delivered. Startle eyeblink responses and subjective reports were assessed in 34 participants during learning. Individuals reporting high SF showed a clear potentiation of the startle response during the interoceptive CS predicting the occurrence of interoceptive threat (US). Such startle potentiation was not observed when the CS remained unpaired (safe or unpredictable context). Moreover, high SF persons also showed a significant startle potentiation to the threatening context, when the CS did not predict the onset of the US. No such learning effects were observed for low SF individuals. The data support the view that defensive response mobilization can be triggered by cues but also by contexts that predict the occurrence of interoceptive threats if these threats are relevant for the individuals, supporting learning accounts for the development of PD.


Assuntos
Asfixia , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Medo/fisiologia , Interocepção/fisiologia , Transtorno de Pânico/fisiopatologia , Reflexo de Sobressalto/fisiologia , Adulto , Dispneia/fisiopatologia , Feminino , Humanos , Masculino , Adulto Jovem
19.
Int J Psychophysiol ; 131: 44-56, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-28947266

RESUMO

Resistant avoidance behaviors play a crucial role in the maintenance of anxiety disorders and are therefore central targets of therapeutic interventions. In the present study, the development of avoidance behavior was investigated in 24 healthy participants who repeatedly prematurely terminated the exposure to increasing interoceptive threat, i.e., the feeling of dyspnea induced by increasing inspiratory resistive loads that were followed by the ultimate threat, a short breathing occlusion. Physiological responses and subjective anxiety preceding terminations were compared to matched intervals of a matched control group (N=24) who completed the exposure. Initially, participants terminated during the ultimate threat, i.e., during occlusion. This first termination was preceded by a strong surge in autonomic arousal and reported anxiety. Startle reflex and the P3 component of event-related brain potentials to startle probes were strongly inhibited, indicating preparation for defensive action. With repetitive terminations, individuals successively terminated earlier, avoiding exposure to the occlusion. This avoidant behavior was accompanied by alleviated autonomic arousal as compared to the first termination. In addition, no indication of physiological response preparation was found implying that the avoidance behavior was performed in a rather habitual way. Matched controls did not show any indication of a defensive response surge in the matched intervals. In matched controls, no changes in physiological response patterns were detected while anxiety levels increased with repetitions. The present results shed new light on our understanding of the motivational basis of avoidance behavior and may help to refine etiological models, behavioral analysis and therapeutic strategies in treating anxiety disorders.


Assuntos
Ansiedade/fisiopatologia , Nível de Alerta/fisiologia , Aprendizagem da Esquiva/fisiologia , Medo/psicologia , Interocepção/fisiologia , Reflexo de Sobressalto/fisiologia , Adulto , Estudos de Casos e Controles , Disfonia/fisiopatologia , Dispneia/fisiopatologia , Eletroencefalografia , Eletromiografia , Potenciais Evocados/fisiologia , Medo/fisiologia , Feminino , Resposta Galvânica da Pele/fisiologia , Frequência Cardíaca/fisiologia , Humanos , Masculino , Respiração , Adulto Jovem
20.
Psychophysiology ; 54(9): 1266-1283, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28466488

RESUMO

In patients with anxiety and/or respiratory diseases, body sensations, particularly from the respiratory system, may increase in intensity and aversiveness and thus lead into defensive action (e.g., escape) or panic. The processes, however, that might contribute to the culmination of symptoms and the switch into defensive action have not been well understood yet. The current study aimed at evaluating an experimental paradigm to characterize the dynamics of defensive mobilization to body sensations increasing in intensity and aversiveness. Persons reporting low and high suffocation fear (SF; N = 69) were exposed to increasingly unpleasant feelings of dyspnea induced by inspiratory resistive loads and a breathing occlusion requiring voluntary breath holding. Respiratory responses were assessed along with subjective reports of anxiety and panic symptoms. Presentation of respiratory loads with increasing physical resistance led to increasingly unpleasant feelings of dyspnea. Twenty-eight participants terminated the exposure prematurely at least once. When dyspnea was severe, high compared to low SF persons exhibited an increased respiratory rate that was accompanied by reports of more intense panic symptoms. Premature terminations of exposure were preceded by a surge in anxiety, breathing frequency, and mouth pressure, and a decrease in tidal volume. We successfully established an experimental paradigm to assess changes in defensive responding with increasing intensity of an interoceptive threat. The current data foster our understanding of behavioral expression patterns observed in patients with anxiety and/or respiratory diseases and the processes involved in the culmination of bodily sensations and anxiety into panic.


Assuntos
Dispneia/fisiopatologia , Medo/fisiologia , Interocepção/fisiologia , Pânico/fisiologia , Respiração , Adulto , Ansiedade/fisiopatologia , Dispneia/psicologia , Medo/psicologia , Feminino , Humanos , Masculino , Mecânica Respiratória/fisiologia , Adulto Jovem
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