Glucocorticoid Receptor Gene (NR3C1) Polymorphisms and Metabolic Syndrome: Insights from the Mennonite Population.

The regulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with polymorphisms and the methylation degree of the glucocorticoid receptor gene (NR3C1) and is potentially involved in the development of metabolic syndrome (MetS). In order to evaluate the association between MetS with the polymorphisms, methylation, and gene expression of the NR3C1 in the genetically isolated Brazilian Mennonite population, we genotyped 20 NR3C1 polymorphisms in 74 affected (MetS) and 138 unaffected individuals without affected first-degree relatives (Co), using exome sequencing, as well as five variants from non-exonic regions, in 70 MetS and 166 Co, using mass spectrometry. The methylation levels of 11 1F CpG sites were quantified using pyrosequencing (66 MetS and 141 Co), and the NR3C1 expression was evaluated via RT-qPCR (14 MetS and 25 Co). Age, physical activity, and family environment during childhood were associated with MetS. Susceptibility to MetS, independent of these factors, was associated with homozygosity for rs10482605*C (OR = 4.74, pcorr = 0.024) and the haplotype containing TTCGTTGATT (rs3806855*T_ rs3806854*T_rs10482605*C_rs10482614*G_rs6188*T_rs258813*T_rs33944801*G_rs34176759*A_rs17209258*T_rs6196*T, OR = 4.74, pcorr = 0.048), as well as for the CCT haplotype (rs41423247*C_ rs6877893*C_rs258763*T), OR = 6.02, pcorr = 0.030), but not to the differences in methylation or gene expression. Thus, NR3C1 polymorphisms seem to modulate the susceptibility to MetS in Mennonites, independently of lifestyle and early childhood events, and their role seems to be unrelated to DNA methylation and gene expression.

Impact of COVID-19 outbreak on Italian healthcare workers versus general population: Results from an online survey.

OBJECTIVE: COVID-19 pandemic has been a stressful condition. We explored life changes and health-related consequences of COVID-19 outbreak in Italian healthcare workers in comparison to the general population. METHODS: A total of 593 subjects participated to the online CoRonavIruS Health Impact Survey. Life events and changes, physical health and worries were evaluated referring to 2 weeks prior to the survey. Mood states and daily behaviour were retrospectively evaluated referring to 3 months before COVID-19 (T1) and 2 weeks prior to the survey (T2). Student t test, Mann-Whitney test and multivariate logistic regression analyses were run. RESULTS: Five hundred and twenty-one subjects were analysed (healthcare workers: n = 163, 31.84%; general population: n = 349, 68.16%). Healthcare workers were more likely to report fatigue and have spent more time outside home during the 2 weeks prior to the survey than the general population (χ2 (df) = 266.03(17) , p < 0.001, R2 = 0.57). From T1 to T2, healthcare workers had a significant increase in negative mood, worry, restlessness, loneliness and a decrease in happiness, while subjects from the general population had a statistically significant increase in negative mood, worry, attention, concentration difficulties and a decrease in happiness, pleasure related to daily activities, time spent outdoors and alcohol use. CONCLUSION: In the framework of a growing literature on healthcare workers' status during the COVID-19 pandemic, the present study allowed to identify fatigue and loneliness as psychosomatic modifiable variables in need of being monitored and, possibly managed, to ameliorate the health status of healthcare workers.

Depression and Health Self-perception: Associations Within the Isolated Mennonite Population in South Brazil.

The Mennonite population suffered several bottlenecks due to religious/political persecution, increasing the frequency of diseases with a strong genetic component. We evaluated health self-perception in 430 Mennonites from South Brazilian settlements (two rural, one urban), along with life habits, xenobiotic exposure, and chronic ilnesses, using a modified version of the 2013 Brazilian National Health Survey and eight psychometric tests (applied in 2016-2018). Mennonites from rural settlements considered their health worse (P < 0.0001). This was independently associated with any psychiatric disease (OR 3.10, P = 0.037), depression diagnosis (OR 2.39, P = 0.002), spinal pain (OR 1.76, P = 0.015), waist circumference (OR 1.02, P = 0.009) and geographic origin (OR 0.64, P = 0.003). In the multivariate analysis including the scales, independent association also occurred with higher anxiety (ASI-R: OR 6.48, P = 0.014) and depression scores (BDI: OR 6.72, P = 0.008). Thus, a worse health self-perception was unequivocally associated with diagnosed or present depression/anxiety, independent of other contributors, suggesting a strong link between both.

The panic disorder respiratory ratio: a dimensional approach to the respiratory subtype.

OBJECTIVE: The respiratory ratio is a dimensional construct of the respiratory subtype of panic disorder (PD). The respiratory subtype has been correlated with an increased sensitivity to CO2 inhalation, positive family history of PD and low comorbidity with depression. The objective of our study was to determine whether the respiratory ratio is correlated with CO2-induced panic attacks and other clinical and demographic features. METHODS: We examined 91 patients with PD and submitted them to a double-breath 35% CO2 challenge test. The respiratory ratio was calculated based on the Diagnostic Symptom Questionnaire (DSQ) scores recorded in a diary in the days preceding the CO2 challenge. The scores of the respiratory symptoms were summed and divided by the total DSQ score. RESULTS: The respiratory ratio was correlated with CO2 sensitivity, and there was a non-statistically significant trend towards a correlation with a family history of PD. CONCLUSIONS: The positive correlation between the respiratory ratio and the anxiety elicited by the CO2 inhalation indicates that the intensity of respiratory symptoms may be proportional to the sensitivity to carbon dioxide.

The panic disorder respiratory ratio: a dimensional approach to the respiratory subtype

OBJECTIVE: The respiratory ratio is a dimensional construct of the respiratory subtype of panic disorder (PD). The respiratory subtype has been correlated with an increased sensitivity to CO2 inhalation, positive family history of PD and low comorbidity with depression. The objective of our study was to determine whether the respiratory ratio is correlated with CO2-induced panic attacks and other clinical and demographic features. METHODS: We examined 91 patients with PD and submitted them to a double-breath 35% CO2 challenge test. The respiratory ratio was calculated based on the Diagnostic Symptom Questionnaire (DSQ) scores recorded in a diary in the days preceding the CO2 challenge. The scores of the respiratory symptoms were summed and divided by the total DSQ score. RESULTS: The respiratory ratio was correlated with CO2 sensitivity, and there was a non-statistically significant trend towards a correlation with a family history of PD. CONCLUSIONS: The positive correlation between the respiratory ratio and the anxiety elicited by the CO2 inhalation indicates that the intensity of respiratory symptoms may be proportional to the sensitivity to carbon dioxide.

Is there a hypersensitive visual alarm system in panic disorder?

Agoraphobia in panic disorder (PD) has been related to abnormal balance system function. Vision influences balance and behavioural adaptations; peripheral vision influences orienting and fast defensive reactions whereas central vision analyzes details of objects. We have hypothesized that the abnormal balance function in PD could be mainly related to peripheral vision as part of a defensive alarm system in the brain. In 25 patients with PD and agoraphobia and 31 healthy controls we assessed, by posturography, balance system reactivity to video-films projected in peripheral and central visual fields (randomized sequence). Length, velocity and surface of body sway were calculated. Patients increased their body sway during peripheral stimulation, whereas controls did not; the two groups showed a similar increase of body sway during central stimulation. Anxiety levels during peripheral stimulation significantly influenced the postural response in the group of patients. These preliminary results suggest that the higher visual sensitivity to peripheral stimulation in patients with PD and agoraphobia may be linked to a more active "visual alarm system" involving visual, vestibular and limbic areas that might influence the development of agoraphobia in situations where environmental stimuli are uncertain.

Medicação antipânico e função pulmonar em pacientes com transtorno de pânico / Antipanic drugs and pulmonary function in panic disorder patients

CONTEXTO: Estudos sugerem uma associação entre transtorno de pânico (TP) e prejuízos na função pulmonar. OBJETIVOS: Avaliar a função pulmonar em 11 pacientes com TP assintomáticos e investigar efeitos da medicação antipânico na função respiratória. MÉTODO: A função pulmonar foi avaliada em duas ocasiões diferentes (com medicação antipânico e após "washout"). Consistiu de uma avaliação espirométrica e do teste de broncodilatação (inalação de salbutamol). Subjective Units of Disturbance Scale (SUDS) foi aplicada antes e após cada teste espirométrico. RESULTADOS: Um paciente apresentou obstrução leve de vias aéreas. Antes do teste de broncodilatação, o volume expiratório forçado no primeiro segundo (VEF1) e o fluxo expiratório forçado entre 25 por cento e 75 por cento da capacidade vital forçada (FEF25-75) foram significativamente maiores em pacientes com medicação antipânico do que no período de "washout". Após a inalação de salbutamol, apenas o VEF1 foi significativamente maior em pacientes com medicação antipânico em comparação ao outro grupo, embora tenha sido detectado aumento significativo em VEF1 e FEF25-75 em pacientes sem medicação antipânico depois da inalação de salbutamol. O nível de ansiedade subjetiva não foi diferente entre os pacientes em ambos os dias de testes. CONCLUSÃO: Os resultados sugerem uma possível ação benéfica da medicação antipânico na função pulmonar em pacientes com TP.

BACKGROUND: Studies suggest an association between panic disorder (PD) and impairment of lung function. OBJECTIVES: To evaluate lung function in 11 asymptomatic PD patients and to investigate antipanic drug effects on respiratory function. METHOD: Lung function was evaluated on two different occasions (with antipanic drugs and after drug washout). It was comprised of a spirometric evaluation and a bronchodilation test (salbutamol inhalation). Subjective Units of Disturbance Scale (SUDS) was applied before and after each spirometric assessment. RESULTS: One patient showed mild obstructive airway impairment. Before bronchodilation test forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25 percent and 75 percent of the forced vital capacity (FEF25-75) were significantly higher in patients on antipanic drugs than in those in the washout period. After salbutamol inhalation, only FEV1 was significantly higher in patients with antipanic drugs in comparison to the other group, whereas a significant increase in FEV1 and FEF25-75 after salbutamol inhalation was detected in patients without antipanic drugs. The subjective anxiety level was not different among PD patients in both test days. DISCUSSION: These results suggest a possible beneficial effect of the antipanic drug on lung function in PD patients.

Quality of life assessment by WHOQOL-BREF in panic disorder patients during treatment / Investigação de qualidade de vida pela WHOQOL-BREF em pacientes com transtorno de pânico durante o tratamento

BACKGROUND: Panic disorder (PD) patients show more physical and psychological impairment, than the general population. OBJECTIVES: Our aims are to compare quality of life between PD patients during treatment and healthy subjects and to associate social, demographic and clinical factors with quality of life scores. METHODS: It is a cross-sectional study with 20 PD patients and 20 healthy controls. Anxiety levels assessment: Beck Anxiety Inventory, Hamilton Anxiety Rating Scale, STAIT - Form Y. Panic severity; Panic Agoraphobia Scale; social and environmental problems and global assessment functioning (Axis IV and V, DSM-IV-TR) and quality of life by WHOQOL-BREF. RESULTS: PD patients were 65 percent female. Mean age = 37.55 ± 9.06. Quality of life domain scores: physical = 57.86 ± 17.56; psychological = 56.04 ± 18.31; social = 56.25 ± 25.92; and environmental = 47.03 ± 16.92; smokers = 20 percent; BAI = 23.40 ± 15; STAI-S= 43.50 ± 8.79; STAI-T = 50.10 ± 9.19; PAS = 13.60 ± 9.40. DISCUSSION: No significant differences were observed between groups about gender, age, schooling, religion, marital status nor individual income, but family income was significantly higher among controls. All domains of quality of life are significantly impaired among PD patients, compared to healthy controls. Panic disorder compromises well being. Psychosocial problems and high levels of anxiety can also negatively impact quality of life of PD patients.

CONTEXTO: Pacientes com transtorno de pânico (TP) apresentam maior comprometimento físico e psicológico que a população geral. OBJETIVOS: Comparar escores de qualidade de vida entre pacientes com TP em tratamento e indivíduos normais. MÉTODOS: Trata-se de estudo transversal com 20 portadores de TP e 20 controles normais. Avaliação da ansiedade inclui: Inventário de Ansiedade de Beck, Escala de Ansiedade de Hamilton, Inventário de Estado e Traço Ansioso, Escala de Pânico e Agorafobia; além de avaliação de problemas sociais e ambientais e funcionamento global (eixos IV e V, DSM-IV-TR) e de qualidade de vida pela WHOQOL-BREF. RESULTADOS: Dos pacientes com TP, 65 por cento eram do sexo feminino. A média de idade foi de 37,55 ± 9,06 anos. Os escores de qualidade de vida foram: físico = 57,86 ± 17,56; psicológico = 56,04 ± 18,31; social = 56,25 ± 25,92; e ambiental 47,03 ± 16,92. Tabagistas = 20 por cento. BAI = 23,40 ± 15; STAI-S = 43,50 ± 8,79; STAI-T = 50,10 ± 9,19; PAS = 13,60 ± 9,40. Não houve diferenças significativas entre os grupos em relação a sexo, idade, escolaridade, religião, estado civil, nem renda individual, porém a renda familiar do grupo-controle foi significativamente maior. Todos os domínios de qualidade de vida foram bem piores entre os pacientes com TP em tratamento, quando comparados aos controles. CONCLUSÕES: TP, mesmo em tratamento, compromete a qualidade de vida. Problemas psicossociais e altos níveis de ansiedade podem ter impacto negativo na qualidade de vida dos pacientes com TP.

O tabagismo e o transtorno do pânico: gravidade e comorbidades / Smoking and panic disorder: severity and comorbidities

INTRODUÇÃO: Estudos indicam que há uma associação entre tabagismo e transtorno do pânico, e alguns autores sugerem que o tabagismo aumenta o risco de ataques de pânico e transtorno do pânico. Este estudo analisa a hipótese de que pacientes fumantes com esse transtorno apresentam um quadro clínico mais grave. MÉTODO: Sessenta e quatro pacientes em tratamento no Laboratório do Pânico e Respiração (Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro), com transtorno do pânico, segundo critérios do Manual de Diagnóstico e Estatística das Perturbações Mentais (DSM, 4ª edição), foram divididos em grupos de tabagistas e não-tabagistas. Os grupos foram avaliados quanto a características sociodemográficas, comorbidades e gravidade do quadro clínico. RESULTADOS: Não houve diferença significativa em relação à gravidade do transtorno do pânico; no entanto, tabagistas tiveram prevalência de depressão significativamente maior (p = 0,014) do que não-tabagistas. CONCLUSÃO: Este estudo não evidenciou que o transtorno do pânico em tabagistas é mais grave, porém indicou que esses pacientes têm mais comorbidade com depressão.

INTRODUCTION: Several studies indicate that panic disorder and tobacco smoking are associated, and some authors hypothesize that smoking increases the risk of panic attacks and panic disorder. The objective of this study is to investigate whether smokers have a more severe form of panic disorder than non-smokers. METHOD: Sixty-four patients already in treatment at the Laboratory of Panic and Respiration (Instituto de Psiquiatria da Universidade Federal do Rio de Janeiro) with panic disorder as established by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were divided into groups of smokers and non-smokers. Both groups were compared regarding sociodemographic data, comorbidities and clinical status severity. RESULTS: There was no statistically significant difference between the two groups regarding severity; however, prevalence of depression was significantly higher in the smoker group than in non-smokers (p = 0.014). CONCLUSION: This study did not indicate that smokers have a more severe form of panic disorder, but smoking and comorbid depression were associated.

Therapeutic response to benzodiazepine in panic disorder subtypes.

CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day), compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001) and decrease in anxiety (p = 0.024). In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes.

Transtorno de pânico e respiração / The panic disorder and respiratory system

O Transtorno do Pânico apresenta-se estreitamente relacionado com o Sistema Respiratório. Os dados atuais desta conexão são apresentados dando-se ênfase aos aspectos fenomenológicos, cognitivos e farmacológicos através de revisão bibliográfica pelo sistema Medline. Foram utilizadas as palavras-chaves pânico, subtipos, fenomenologia, sintomas, cognição e tratamento farmacológico. Subtipos distintos do pânico constam na literatura divergindo em relação aos padrões sintomáticos, farmacológicos e de restividade ao dióxido de carbono. Interpretações catastróficas de sintomas somáticos e/ou a perda do senso de controle podem contribuir para os sintomas do pãnico. A importância de cada um destes fatores e a forma como se correlacionam sugerem uma via comum de sintomas respiratórios e ansiedade, através de mecanismos que ainda precisam ser melhor elucidados.A teoria do Falso Alarme de Sufocação de Donald Klein desempenha um papel central na interface apontando explicações para os efeitos panicogênicos dos testes laboratoriais. Uma vez que o lactato e o dióxido de carbono são produtos metabólitos finais, o alarme de sufocação funcionaria através de um auto-monitoramento dos níveis destas substâcias. A provocação com CO2 tem demonstrado como experimentos laboriatorais podem contribuir para a psicopatologia clínica.

Therapeutic response to benzodiazepine in panic disorder subtypes

CONTEXT: This study makes a comparison between two subtypes of panic disorder regarding the clinical efficacy of clonazepam, a benzodiazepine. OBJECTIVES: To evaluate the clinical efficacy of clonazepam in a fixed dosage (2 mg/day), compared to placebo, in the treatment of panic disorder patients and to verify whether there are any differences in the responses to clonazepam between panic disorder patients with the respiratory and non-respiratory subtypes. TYPE OF STUDY: Randomized study with clonazepam and placebo. SETTING: Outpatient Anxiety and Depression Unit of the Institute of Psychiatry, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. PARTICIPANTS: 34 patients with a diagnosis of panic disorder with agoraphobia, between 18 and 55 years old. PROCEDURES: Administration of clonazepam or placebo for 6 weeks, in panic disorder patients, after they were classified within two subtypes of panic disorder: respiratory and non-respiratory. MAIN MEASUREMENTS: Changes in the number of panic attacks in comparison with the period before the beginning of the study; Hamilton Anxiety Scale; Global Clinical Impression Scale; and Patient's Global Impression scale. RESULTS: In the group that received clonazepam, by the end of the 6th week there was a statistically significant clinical improvement, shown by the remission of panic attacks (p < 0.001) and decrease in anxiety (p = 0.024). In the group that received clonazepam there was no significant difference between the respiratory and non-respiratory subtypes of panic disorder, regarding the therapeutic response to clonazepam. CONCLUSION: Clonazepam was equally effective in the treatment of the respiratory and non-respiratory subtypes of panic disorder, suggesting there is no difference in the therapeutic response between the two subtypes

A interface pânico e respiração / The panico and respiration connection

O transtorno do pânico apresenta-se estreitamente relacionado com o sistema respiratório. Os dados atuais desta conexão são apresentados, dando-se ênfase aos aspectos fenomenológicos, cognitivos e farmacológicos através de revisão bibliográfica pelo sistema Medline. Foram utilizadas as palavras-chaves pânico, subtipos, fenomenologia, sintomas, cognição e tratamento farmacológico, durante o período de 1980 a 2000. Subtipos distintos do pânico constam na literatura divergindo em relação aos padrões sintomáticos, farmacológicos e de reatividade ao dióxido de carbono. Interpretações catastróficas de sintomas somáticos e/ou a perda do senso de controle podem contribuir para os sintomas do pânico. A importância de cada um destes fatores e a forma como se correlacionam sugerem uma via comum de sintomas respiratórios e ansiedade, através de mecanismos que ainda precisam ser melhor elucidados. A teoria do falso alarme de sufocação, de Donald Klein, desempenha um papel central na interface, apontando explicações para os efeitos panicogênicos dos testes laboratoriais. Uma vez que o lactato e o dióxido de carbono são produtos metabólito finais, o alarme de sufocação funcionaria através de um auto-monitoramento dos níveis destas substâncias. A provocação com CO2 tem demonstrado como experimentos laboratoriais podem contribuir para a psicopatologia clínica