RESUMO
Importance: This report details a case of effectively managing severe panic attacks in a panic disorder (PD) patient with agoraphobia by acupuncture treatment. Case presentation: A 38-year-old Japanese woman suffering from PD with agoraphobia presented at our acupuncture clinic with complaints of repeated panic attacks and anxiety. Initially starting to experience symptoms in her late teens, she avoided psychiatric consultation due to reluctance toward psychotropic medications. An unbiased psychiatrist used the Panic Disorder Severity Scale (PDSS) to assess her PD severity. The PDSS score decreased from 21 on the first to 12 points on the sixth visit. The patient experienced reduced frequency and severity of panic attacks, with restored confidence to go into public despite agoraphobia. Conclusions and Relevance: This is the first report to demonstrate the effectiveness of acupuncture on PD with agoraphobia using PDSS, suggesting its potential as a nonpharmacological treatment for patients with PD and agoraphobia.
Assuntos
Terapia por Acupuntura , Agorafobia , Transtorno de Pânico , Humanos , Transtorno de Pânico/terapia , Transtorno de Pânico/psicologia , Agorafobia/terapia , Agorafobia/psicologia , Agorafobia/complicações , Feminino , Adulto , Resultado do TratamentoRESUMO
In humans, adverse physical and/or psychological traumas in childhood may predispose to developing psychiatric disorders in adulthood, including panic disorder. To model early life adversity in mice, we subjected male and female C57BL/6 J mice to a limited bedding and nesting (LBN) protocol between postnatal days 2-9 and investigated its effect on responsiveness to panicogenic challenges in adulthood. Panic-like escape behaviour was assessed during exposure to a high concentration of CO2 (20%) or in the beetle mania task (BMT), used to model respiratory and non-respiratory-related types of panic respectively. Neonatal exposure to LBN increased panic-like jumping during the CO2 challenge in male but not female mice. In an initial pharmacological validation of the BMT as a panic-inducing paradigm, undirected jumping and horizontal escape behaviours were reduced significantly by the panicolytic alprazolam (0.05 and 0.1mg.kg-1 i.p.) whilst tolerance to the close proximity of the aversive robo-beetle increased. The anxiolytic diazepam (1 mg.kg-1 i.p.) reduced only the number of horizontal escape attempts. In both sexes, previous experience of LBN significantly enhanced the number of horizontal escape episodes, indicating a pro-panic phenotype. Directed escape to access a safe ledge on the wall of the test arena, which was seen only in males, was also reduced significantly following LBN. These findings indicate that early life adversity produced by fragmented and unpredictable maternal care promotes a sex-specific increase in susceptibility to panic-like behaviour in adulthood. Whilst non-respiratory-related panic-like behaviour was enhanced in both sexes, females were resilient to respiratory-related challenges.
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Animais Recém-Nascidos , Camundongos Endogâmicos C57BL , Animais , Feminino , Masculino , Camundongos , Comportamento de Nidação/efeitos dos fármacos , Comportamento de Nidação/fisiologia , Pânico/efeitos dos fármacos , Pânico/fisiologia , Transtorno de Pânico , Caracteres Sexuais , Alprazolam/farmacologia , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Diazepam/farmacologia , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Dióxido de Carbono/farmacologiaRESUMO
The role of schemas is well established in personality disorders. Their influence on therapy outcome of patients with Axis I disorders remains unclear. Therefore, patients with a panic disorder (PD) with/without agoraphobia varying in their expression of early maladaptive schemas were examined regarding therapy outcomes after exposure therapy. In this study, a sample of 216 patients with panic disorder with/without agoraphobia were recruited in a day clinic. After the initial diagnosis with the Structured Clinical Interview, the patients filled out the Young Schema Questionnaire (YSQ-S2), Beck Depression Inventory and Revised Symptom Checklist. Afterwards, they participated in a five-week manualized exposure therapy by Lang et al. (2011). Subjects with high schema scores showed lower therapeutic success rates than subjects with a weaker pattern score. In addition, it was found that high schema levels, especially of schemas regarding impaired autonomy and achievement (YSQ-S2: domain 2), influenced therapy outcome by either predicting more/severe or less/milder anxiety-, phobicrelated and general symptoms after therapy. The results of this study emphasize the role of schemas not only for personality disorders but also for disorders on Axis I. For PD with/without agoraphobia, schemas regarding impaired autonomy and achievement seem to play the most important role regarding the influence on therapy outcome.
Assuntos
Agorafobia , Terapia Implosiva , Transtorno de Pânico , Humanos , Transtorno de Pânico/terapia , Transtorno de Pânico/psicologia , Transtorno de Pânico/diagnóstico , Feminino , Agorafobia/terapia , Agorafobia/psicologia , Agorafobia/diagnóstico , Masculino , Adulto , Resultado do Tratamento , Psicometria , Pessoa de Meia-Idade , Adulto Jovem , Inventário de Personalidade/estatística & dados numéricosRESUMO
Objective: The association between childhood separation anxiety disorder (CSAD) and panic disorder (PD) has been demonstrated, although some findings are contradictory. The separation anxiety hypothesis postulates that both CSAD and PD encompass a heightened sensitivity to carbon dioxide (CO2). Patients with the respiratory subtype (RS) of PD are known to be more sensitive to CO2 than those from the nonrespiratory subtype (NRS). Therefore, the primary objective centered on the comparative analysis of CSAD prevalence between RS and NRS groups, with secondary objectives focusing on the comparative assessment of RS and NRS groups and the control group.Methods: Sixty RS-PD patients, 60 NRS-PD patients, and 60 controls were assessed for retrospective diagnosis of CSAD between March 2020 and August 2023 using a diagnostic categorical instrument, DSM-5 criteria, and a dimensional one, the Separation Anxiety Symptom Inventory.Results: RS patients had a significantly greater history of CSAD (55%) compared to the NRS (23%) and control (17%) groups (P < .001), which shows stronger association with the RS group. As seen in logistic regression, RS patients had 3.02 more chances of having CSAD when compared the NRS group and 5.11 when compared to the control group, which shows stronger association with the RS group.Conclusion: This study supports the hypothesis that RS-PD is associated with CSAD, while there is a weak association between NRS-PD and CSAD. It is advisable for clinicians to screen individuals with RS-PD for symptoms of separation anxiety, as these symptoms may have a negative impact on the prognosis of PD.Prim Care Companion CNS Disord 2024;26(5):24m03709. Author affiliations are listed at the end of this article.
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Ansiedade de Separação , Transtorno de Pânico , Humanos , Masculino , Feminino , Estudos Retrospectivos , Criança , Adulto , Adolescente , PrevalênciaRESUMO
HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.
Assuntos
Predisposição Genética para Doença , Transtorno de Pânico , Receptor 5-HT1A de Serotonina , Proteínas da Membrana Plasmática de Transporte de Serotonina , Humanos , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Transtorno de Pânico/genética , Receptor 5-HT1A de Serotonina/genética , Polimorfismo de Nucleotídeo Único , População Branca/genéticaRESUMO
BACKGROUND: The cognitive theory of panic disorder proposes that individuals with panic disorder have a relatively enduring tendency to catastrophically misinterpret bodily sensations resulting in panic attacks. AIMS: We investigated whether the evidence is consistent with the theory and its predictions, if updates are required and sought to identify future research considerations. METHODS: We searched Scopus, Web of Science, PsycInfo, EMBASE, MEDLINE and CINAHL (1986 to July 2024). Inclusion criteria were studies collecting quantitative data derived from panic disorder patients, testing one of the predictions and using appropriate outcome measures. Exclusion criteria were non-English language publications, all participants under the age of 18 and studies that were not published in a peer-reviewed journal. Quality was assessed using 'QualSyst' and synthesis was based on each prediction tested. PROPSERO registration #CRD42022332211. RESULTS: 53 studies were identified amongst 49 publications. There was substantial evidence for all predictions. Three studies did not support the prediction tested and none were inconsistent. LIMITATIONS: Most studies were 'medium' in quality and were predominately from female samples. CONCLUSIONS: Findings are consistent with the theory and its predictions. Higher quality research is needed and implications for future research are discussed.
Assuntos
Transtorno de Pânico , Teoria Psicológica , Humanos , Transtorno de Pânico/psicologia , Cognição/fisiologia , Catastrofização/psicologiaRESUMO
PURPOSE: This study examined the relationship between structural brain networks and long-term treatment outcomes in patients with panic disorder (PD) using machine learning methods. METHOD: The study involved 80 participants (53 PD patients and 27 healthy controls) and included clinical assessments and MRI scans at baseline and after two years (160 MRIs). Patients were categorized based on their response to two-year pharmacotherapy. Brain networks were analyzed using white matter tractography and network-based statistics. RESULTS: Results showed structural network changes in PD patients, particularly in the extended fear network, including frontal regions, thalamus, and cingulate gyrus. Longitudinal analysis revealed that increased connections to the amygdala, hippocampus, and insula were associated with better treatment response. Conversely, overconnectivity in the amygdala and insula at baseline was associated with poor response, and similar patterns were found in the insula and parieto-occipital cortex related to non-remission. This study found that SVM and CPM could effectively predict treatment outcomes based on network pattern changes in PD. CONCLUSIONS: These findings suggest that monitoring structural connectome changes in limbic and paralimbic regions is critical for understanding PD and tailoring treatment. The study highlights the potential of using personalized biomarkers to develop individualized treatment strategies for PD.
Assuntos
Conectoma , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Transtorno de Pânico , Humanos , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/terapia , Masculino , Feminino , Adulto , Estudos Longitudinais , Resultado do Tratamento , Estudos Transversais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Pessoa de Meia-Idade , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Imagem de Tensor de Difusão/métodos , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
According to biopsychosocial models, experiencing parental child abuse increases susceptibility to adulthood psychopathology. However, there is a paucity of studies examining potential mechanisms of the parental child abuse and adulthood psychopathology relationship. The purpose of the current study was to determine if Time 2 (T2) trait self-esteem mediated levels of Time 1 (T1) retrospectively recalled parental child abuse predicting (T3) past-year major depressive disorder (MDD), generalized anxiety disorder (GAD), panic disorder (PD), alcohol use disorder (AUD), and substance use disorder (SUD) symptoms. The 18-year Midlife Development in the United States (MIDUS) study included participants (N = 3294; T1 average age of 45.62 years) assessed at three different time points, each spaced about nine years apart. We performed structural equation mediation modeling analyses to determine how maternal and paternal child abuse at T1 would independently predict T3 MDD, GAD, PD, AUD, and SUD symptoms. We also examined whether T2 self-esteem mediated these relations while controlling for adulthood T1 psychopathology symptoms, demographics, socioeconomic status, somatic symptoms, and parental psychopathology. Consistent with our hypotheses, higher T1 maternal and paternal abuse predicted increased T3 GAD, PD, AUD, and SUD symptoms via diminished T2 self-esteem as the mediator (% proportion mediated = 33.0-100). However, childhood paternal, but not maternal, abuse predicted adulthood MDD symptoms via reduced self-esteem. Findings remained after adjusting for covariates. Our research highlights the importance of understanding retrospectively recalled parental child abuse-adulthood psychopathology relations, their potential mechanisms, and self-esteem as a malleable treatment target for adults with heightened child abuse.
Assuntos
Transtornos de Ansiedade , Transtorno Depressivo Maior , Autoimagem , Transtornos Relacionados ao Uso de Substâncias , Humanos , Feminino , Masculino , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Pessoa de Meia-Idade , Adulto , Transtornos de Ansiedade/psicologia , Transtornos de Ansiedade/epidemiologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/epidemiologia , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Sobreviventes Adultos de Maus-Tratos Infantis/estatística & dados numéricos , Transtorno de Pânico/psicologia , Transtorno de Pânico/epidemiologia , Maus-Tratos Infantis/psicologia , Maus-Tratos Infantis/estatística & dados numéricos , Estados Unidos/epidemiologia , Criança , Ansiedade/psicologia , Ansiedade/epidemiologia , Depressão/psicologia , Depressão/epidemiologia , Alcoolismo/psicologia , Alcoolismo/epidemiologiaRESUMO
OBJECTIVE: Patients who have experienced child abuse often have complex clinical presentations; whether a history of child abuse (HCA) affects psychotherapy outcomes is unclear. The authors examined relationships between HCA, clinical baseline variables, and change in these variables after three different psychotherapies for panic disorder (PD). METHODS: Two hundred adults with PD (with or without agoraphobia) were randomly assigned to one of three treatments across two sites: panic-focused psychodynamic psychotherapy (PFPP), cognitive-behavioral therapy (CBT), or applied relaxation training (ART). Differences in demographic and clinical variables between those with and without HCA were compared. The primary analysis addressed odds of meeting clinical response criteria on the Panic Disorder Severity Scale (PDSS) between treatments, as moderated by HCA. This effect was examined via continuous outcomes on the PDSS and psychosocial functioning (Sheehan Disability Scale). RESULTS: Compared with patients without HCA (N=154), patients with HCA (N=46) experienced significantly more severe symptoms of PD (d=0.60), agoraphobia (d=0.47), and comorbid depression (d=0.46); significantly worse psychosocial impairment (d=0.63) and anxiety sensitivity (d=0.75); greater personality disorder burden (d=0.45)-particularly with cluster C disorders (d=0.47)-and more severe interpersonal problems (d=0.54). HCA significantly moderated the likelihood of clinical response, predicting nonresponse to ART (B=-2.05, 95% CI=-4.17 to -0.30, OR=0.13, z=-2.14, p=0.032) but not CBT or PFPP. HCA did not interact with treatment condition to predict slopes of PDSS change. CONCLUSIONS: The results of this study highlight the importance of HCA in formulating treatment recommendations. Increased awareness of HCA's effects on severity of PD and treatment responsiveness among patients with PD may improve outcomes.
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Terapia Cognitivo-Comportamental , Transtorno de Pânico , Psicoterapia Psicodinâmica , Índice de Gravidade de Doença , Humanos , Transtorno de Pânico/terapia , Transtorno de Pânico/psicologia , Transtorno de Pânico/complicações , Feminino , Masculino , Adulto , Terapia Cognitivo-Comportamental/métodos , Resultado do Tratamento , Terapia de Relaxamento , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Agorafobia/terapia , Agorafobia/psicologia , Agorafobia/complicações , Pessoa de Meia-Idade , CriançaRESUMO
Current medications for panic disorder each carry significant limitations that indicate the need for novel anxiolytics. The high costs and low success rates of drug development demand that testing trials be efficient. Lab panicogenic challenges in humans allow for the rapid biochemical induction of panic symptoms and hence an efficient means of testing potential anti-panic drugs. This paper describes ideal characteristics of lab panicogens, reviews the validity and utility of various biochemical panicogenic agents, identifies key outcome measures for studies of novel anti-panic drugs, and makes broad recommendations for labs wishing to perform such studies. We conclude by presenting a four-tiered hierarchy of panicogens that matches each against ideal characteristics and reflects our recommendations for their laboratory use.
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Ansiolíticos , Transtorno de Pânico , Humanos , Transtorno de Pânico/tratamento farmacológico , Ansiolíticos/farmacologia , Animais , Pânico/efeitos dos fármacosRESUMO
This systematic review addresses the complex nature of Panic Disorder (PD), characterized by recurrent episodes of acute fear, with a focus on updating and consolidating knowledge regarding neurochemical, genetic, and epigenetic factors associated with PD. Utilizing the PRISMA methodology, 33 original peer-reviewed studies were identified, comprising 6 studies related to human neurochemicals, 10 related to human genetic or epigenetic alterations, and 17 animal studies. The review reveals patterns of altered expression in various biological systems, including neurotransmission, the Hypothalamic-Pituitary-Adrenal (HPA) axis, neuroplasticity, and genetic and epigenetic factors leading to neuroanatomical modifications. Noteworthy findings include lower receptor binding of GABAA and serotonin neurotransmitters in the amygdala. The involvement of orexin (ORX) neurons in the dorsomedial/perifornical region in triggering panic reactions is highlighted, with systemic ORX-1 receptor antagonists blocking panic responses. Elevated Interleukin 6 and leptin levels in PD patients suggest potential connections between stress-induced inflammatory changes and PD. Brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB) signaling are implicated in panic-like responses, particularly in the dorsal periaqueductal gray (dPAG), where BDNF's panicolytic-like effects operate through GABAA-dependent mechanisms. GABAergic neurons' inhibitory influence on dorsomedial and posterior hypothalamus nuclei is identified, potentially reducing the excitability of neurons involved in panic-like responses. The dorsomedial hypothalamus (DMH) is highlighted as a specific hypothalamic nucleus relevant to the genesis and maintenance of panic disorder. Altered brain lactate and glutamate concentrations, along with identified genetic polymorphisms linked to PD, further contribute to the intricate neurochemical landscape associated with the disorder. The review underscores the potential impact of neurochemical, genetic, and epigenetic factors on the development and expression of PD. The comprehensive insights provided by this systematic review contribute to advancing our understanding of the multifaceted nature of Panic Disorder and pave the way for targeted therapeutic strategies.
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Sistema Hipotálamo-Hipofisário , Transtorno de Pânico , Humanos , Transtorno de Pânico/genética , Transtorno de Pânico/metabolismo , Animais , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismo , Orexinas/metabolismo , Orexinas/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Epigênese GenéticaRESUMO
Importance: The persistent stigma associated with mental health conditions is a major challenge worldwide. Celebrities may improve this by openly discussing their own mental health issues, potentially influencing public attitudes and encouraging individuals to seek treatment for these conditions. Objective: To evaluate the impact of celebrity mental health disclosures on the incidence and prevalence of panic disorder diagnosis in South Korea. Design, Setting, and Participants: This cohort study included the entire South Korean population from January 2004 to December 2021, as reflected in the National Health Insurance Service data. Analysis was conducted from May 2022 through January 2024. Exposure: Time periods analyzed included the timeframe before (from January 2004 to December 2010) and after the public disclosures of panic disorder by 3 high-profile Korean celebrities between December 2010 and January 2012 (from January 2011 to December 2021). Main Outcomes and Measures: Monthly incidence and prevalence of panic disorder, defined by the presence of a clinical diagnosis of the condition. Trends were assessed using interrupted time series analysis with autoregressive integrated moving average models. To assess public interest in panic disorder, trends in search data were analyzed, examining the association between the timing of increased searches and changes in the incidence and prevalence of panic disorder. Data on obsessive-compulsive disorder (OCD) were included as a control. Results: The study covered the entire population of South Korea, including 48â¯559â¯946 individuals in January 2004 and 52â¯593â¯886 individuals in December 2021. Before 2011, the mean (SD) annual prevalence of panic disorder was stable at 560 (140) persons per 100â¯000 persons per year. The celebrity disclosure in December 2010 was associated with higher monthly incidence rates of panic disorder, as measured by insurance claims data, changes that were observed in both the level (5.8 persons; 95% CI, 2.2-9.5 persons) and slope (0.78 persons per month; 95% CI, 0.19-1.40 persons per month) per 100â¯000 persons. By 2021, the observed annual prevalence per 100â¯000 persons reached 7530 persons, an increase of 775.6% compared with the 860 persons (95% CI, 330-1400 persons) estimated if the disclosures had not occurred. Internet searches anticipated changes in monthly prevalence with a lag of 2 or 3 months (F = 4.26, P = .02 and F = 3.11, P = .03, respectively). The celebrity disclosures had no significant association with the incidence or prevalence of OCD. Conclusions and Relevance: In this observational cohort study, celebrity disclosure of mental health conditions was associated with a sustained reduction in stigma, as reflected in increased help-seeking behavior for the condition over more than a decade. This underscores the influential role celebrities can play in shaping public health perceptions and behaviors, offering valuable insights for the development of future mental health policies and public awareness campaigns.
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Pessoas Famosas , Transtorno de Pânico , Humanos , República da Coreia/epidemiologia , Transtorno de Pânico/epidemiologia , Incidência , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prevalência , Revelação/estatística & dados numéricos , Estudos de Coortes , Estigma SocialRESUMO
Generalized Anxiety Disorder (GAD) presents a significant personal and societal burden and is associated with chronic medical comorbidities and markedly lower quality of life. Effective treatments exist, less than half of individuals with lifetime GAD will ever seek psychotherapeutic or pharmacological treatment. A thorough understanding of the factors that influence treatment seeking for GAD is warranted. The present study investigates the correlates of GAD treatment seeking, using data from the National Epidemiological Survey on Alcohol and Related Disorders-III (NESARC-III), which assessed for psychiatric disorders using the Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-5 Version (AUDADIS-5). A series of logistic regressions were run to identify demographic, diagnostic, and symptom-level correlates of treatment seeking in those meeting DSM-5 diagnostic criteria for GAD. Comorbid depression, panic disorder, and PTSD were all uniquely associated with higher rates of GAD-related treatment seeking. Additionally, several accompanying anxiety symptoms were also uniquely predicted treatment seeking, including fatigue, panic attacks, reassurance-seeking, and interpersonal avoidance. Findings underscore the multi-factorial nature of treatment seeking behavior in GAD and highlight the need for further research to fully understand these relationships and devise effective strategies to improve treatment seeking in this population.
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Transtornos de Ansiedade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Masculino , Feminino , Transtornos de Ansiedade/epidemiologia , Transtornos de Ansiedade/diagnóstico , Transtornos de Ansiedade/terapia , Adulto , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Comorbidade , Adolescente , Adulto Jovem , Inquéritos Epidemiológicos , Idoso , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia , Transtorno de Pânico/epidemiologia , Transtorno de Pânico/diagnóstico , Transtorno de Pânico/terapia , Estados Unidos/epidemiologiaRESUMO
Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention.
Assuntos
Medo , Imageamento por Ressonância Magnética , Transtorno de Pânico , Humanos , Transtorno de Pânico/fisiopatologia , Transtorno de Pânico/diagnóstico por imagem , Transtorno de Pânico/patologia , Masculino , Adulto , Feminino , Medo/fisiologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Rede Nervosa/patologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Encéfalo/patologia , Pessoa de Meia-Idade , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/fisiopatologia , Tonsila do Cerebelo/patologia , Adulto Jovem , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Substância Cinzenta/fisiopatologiaRESUMO
BACKGROUND: Observational data indicates a connection between emotional discomfort, such as anxiety and depression, and uterine fibroids (UFs). However, additional investigation is required to establish the causal relationship between them. Hence, we assessed the reciprocal causality between four psychological disorders and UFs utilizing two-sample Mendelian randomization (MR). METHODS: To evaluate the causal relationship between four types of psychological distress (depressive symptoms, severe depression, anxiety or panic attacks, mood swings) and UFs, bidirectional two-sample MR was employed, utilizing single nucleotide polymorphisms (SNPs) associated with these conditions. Both univariate MR (UVMR) and multivariate MR (MVMR) primarily applied inverse variance weighted (IVW) as the method for estimating potential causal effects. Complementary approaches such as MR Egger, weighted median, simple mode, and weighted mode were utilized to validate the findings. To assess the robustness of our MR results, we conducted sensitivity analyses using Cochran's Q-test and the MR Egger intercept test. RESULTS: The results of our UVMR analysis suggest that genetic predispositions to depressive symptoms (Odds Ratio [OR] = 1.563, 95% Confidence Interval [CI] = 1.209-2.021, P = 0.001) and major depressive disorder (MDD) (OR = 1.176, 95% CI = 1.044-1.324, P = 0.007) are associated with an increased risk of UFs. Moreover, the IVW model showed a nominally significant positive correlation between mood swings (OR: 1.578; 95% CI: 1.062-2.345; P = 0.024) and UFs risk. However, our analysis did not establish a causal relationship between UFs and the four types of psychological distress. Even after adjusting for confounders like body mass index (BMI), smoking, alcohol consumption, and number of live births in the MVMR, the causal link between MDD and UFs remained significant (OR = 1.217, 95% CI = 1.039-1.425, P = 0.015). CONCLUSIONS: Our study presents evidence supporting the causal relationship between genetic susceptibility to MDD and the incidence of UFs. These findings highlight the significance of addressing psychological health issues, particularly depression, in both the prevention and treatment of UFs.
Assuntos
Depressão , Leiomioma , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Humanos , Análise da Randomização Mendeliana/métodos , Feminino , Leiomioma/genética , Leiomioma/psicologia , Depressão/epidemiologia , Depressão/genética , Depressão/psicologia , Angústia Psicológica , Predisposição Genética para Doença/psicologia , Ansiedade/epidemiologia , Ansiedade/psicologia , Neoplasias Uterinas/genética , Neoplasias Uterinas/psicologia , Causalidade , Transtorno de Pânico/genética , Transtorno de Pânico/psicologia , Transtorno de Pânico/epidemiologiaRESUMO
CO2 exposure has been used to investigate the panicogenic response in patients with panic disorder. These patients are more sensitive to CO2, and more likely to experience the "false suffocation alarm" which triggers panic attacks. Imbalances in locus coeruleus noradrenergic (LC-NA) neurotransmission are responsible for psychiatric disorders, including panic disorder. These neurons are sensitive to changes in CO2/pH. Therefore, we investigated if LC-NA neurons are differentially activated after severe hypercapnia in mice. Further, we evaluated the participation of LC-NA neurons in ventilatory and panic-like escape responses induced by 20% CO2 in male and female wild type mice and two mouse models of altered LC-NA synthesis. Hypercapnia activates the LC-NA neurons, with males presenting a heightened level of activation. Mutant males lacking or with reduced LC-NA synthesis showed hypoventilation, while animals lacking LC noradrenaline present an increased metabolic rate compared to wild type in normocapnia. When exposed to CO2, males lacking LC noradrenaline showed a lower respiratory frequency compared to control animals. On the other hand, females lacking LC noradrenaline presented a higher tidal volume. Nevertheless, no change in ventilation was observed in either sex. CO2 evoked an active escape response. Mice lacking LC noradrenaline had a blunted jumping response and an increased freezing duration compared to the other groups. They also presented fewer racing episodes compared to wild type animals, but not different from mice with reduced LC noradrenaline. These findings suggest that LC-NA has an important role in ventilatory and panic-like escape responses elicited by CO2 exposure in mice.
Assuntos
Dióxido de Carbono , Hiperventilação , Locus Cerúleo , Norepinefrina , Animais , Locus Cerúleo/metabolismo , Locus Cerúleo/efeitos dos fármacos , Feminino , Masculino , Norepinefrina/metabolismo , Camundongos , Hipercapnia/metabolismo , Camundongos Endogâmicos C57BL , Pânico/efeitos dos fármacos , Pânico/fisiologia , Modelos Animais de Doenças , Transtorno de Pânico/metabolismo , Transtorno de Pânico/induzido quimicamente , Transtorno de Pânico/fisiopatologia , Camundongos Knockout , Caracteres SexuaisRESUMO
Social anxiety disorder (SAD) and panic disorder (PD) are prevalent anxiety disorders characterized by a complex interplay of genetic and environmental factors. Both disorders share overlapping features and often coexist, despite displaying distinct characteristics. Childhood life adversity, overall stressful life events, and genetic factors contribute to the development of these disorders. DNA methylation, an epigenetic modification, has been implicated in the pathogenesis of these diseases. In this study, we investigated whether whole-genome DNA methylation risk scores (MRSs) for SAD risk, severity of social anxiety, childhood life adversity, PD risk, and overall stressful life events were associated with SAD or PD caseâcontrol status. Preliminary epigenome-wide association studies (EWASs) for SAD risk, severity of social anxiety, and childhood life adversity were conducted in 66 SAD individuals and 77 healthy controls (HCs). Similarly, EWASs for PD risk and overall stressful life events were performed in 182 PD individuals and 81 HCs. MRSs were calculated from these EWASs. MRSs derived from the EWASs of SAD risk and severity of social anxiety were greater in PD patients than in HCs. Additionally, MRSs derived from the EWASs of overall stressful life events, particularly in PD individuals, were lower in SAD individuals than in HCs. In contrast, MRSs for childhood life adversity or PD risk were not significantly associated with PD or SAD caseâcontrol status. These findings highlight the epigenetic features shared in both disorders and the distinctive epigenetic features related to social avoidance in SAD patients, helping to elucidate the epigenetic basis of these disorders.
Assuntos
Experiências Adversas da Infância , Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Transtorno de Pânico , Fobia Social , Estresse Psicológico , Humanos , Transtorno de Pânico/genética , Masculino , Feminino , Adulto , Fobia Social/genética , Estresse Psicológico/genética , Estudos de Casos e Controles , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Musculoskeletal chronic pain is a leading cause of global disability and laboral incapacity. However, there is a lack of population-based studies that investigate the relationship between chronic pain and mental disorders with a control group, particularly among low- and middle-income countries. Chronic pain is a serious public health problem in terms of human suffering, and in terms of socioeconomic implications. Frequent association with different mental disorders increases disability, decreases quality of life, and makes diagnosis and treatment challenging. The present study aimed to evaluate the presence of mental disorders in patients with chronic musculoskeletal pain and compare with a control group without pain. METHODS: We selected 100 patients in a regular follow-up at the Musculoskeletal Pain Outpatient Clinic of the University Hospital and compared them with 100 painless individuals from the control group from June 2016 to June 2018. The instruments used were the Mini International Neuropsychiatric Interview (MINI-PLUS) and a structured questionnaire to collect sociodemographic data. Statistical analysis used t-test, chi-square, Fisher's exact test, Mann-Whitney, Kolmogorov-Smirnov tests, and multiple logistic regression. RESULTS: In the sample evaluated, the majority of patients were women (83%), of brown color (54%), with lower-level education (51%), lower salary range (73%) and high absenteeism rate at work (60,7%). Patients with chronic pain had more psychiatric disorders (88% vs. 48% in the control group; p < 0.001). The most frequent diagnoses were anxiety disorders with panic attacks (44%), generalized anxiety (36%), mixed anxiety and depression disorder (33%), social phobia (30%), agoraphobia (29%), suicide risk (28%), and major depression (27%). CONCLUSION: Positive correlations of mental disorders and chronic musculoskeletal pain have been documented. This suggests that psychiatric components must be taken into account in the management of chronic pain syndromes. The use of Mini Plus as a diagnostic tool for psychiatric disorders can contribute to optimizing the diagnosis and treatment of patients with chronic pain and encourage the creation of policies with strategies and criteria for quick access to Multi-professional Services.