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Introduction: In patients affected by atrial fibrillation (AF) disease-specific knowledge and coping style may be associated with psychosocial well-being. This study aimed to determine if coping style (problem-focused, emotion-focused, avoidance-focused) mediated the relationship between patient knowledge and three psychosocial outcomes (anxiety, depression and life satisfaction). Methods: In 2021 a total of 188 women with reported AF, and ages ranging from 18 to 83 years (mean 48.7, sd 15.5 years), completed an online questionnaire consisting of sociodemographic, clinical and AF knowledge questions and psychosocial instruments (Anxiety and depression, the Hospital Anxiety and Depression (HADS) scale; life satisfaction, Satisfaction With Life Scale (SWLS); and coping style (Brief COPE). Using Jamovi statistical software three individual mediational models (for anxiety, depression and life satisfaction) were constructed assessing the direct and indirect relationships between knowledge, coping style and each psychosocial outcome. Age was a covariate in each model. Results: The mediation analyses demonstrated significant direct negative associations between AF knowledge and HADS anxiety and depression and positive associations with SWLS. There were also direct associations between each of the three coping styles and the three psychosocial outcomes. There were significant indirect effects of coping style between AF knowledge and each of the three outcomes confirming partial mediation effects. Discussion: These findings highlight the crucial role of coping style in mediating the association between AF knowledge and psychosocial outcomes. As such, interventions aimed at increasing patient knowledge of AF may be more effective if adaptive problem-solving coping strategies are also demonstrated to these patients. Additionally, modification of maladaptive coping strategies as part of the psychological management of patients with AF is highly recommended.
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IMPORTANCE: Physical activity during menopause can be effective in reducing the physiological changes associated with reproductive aging that increase risks for noncommunicable diseases, yet many women do not meet the recommendations for physical activity. OBJECTIVE: This study aimed to synthesize factors influencing physical activity for women across menopausal transition phases using a socioecological approach. EVIDENCE REVIEW: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis was used to systematically search 10 databases between 2001 and 2021. A comprehensive search strategy was used to identify studies on physical activity of women in various stages of menopause. A socioecological model was used to categorize the reported barriers and enablers. FINDINGS: Twenty studies met the inclusion criteria. The findings highlight several intrapersonal barriers such as existing health complaints versus enablers such as awareness of the health benefits of physical activity during menopause. Ensuring women's safety, preventing injury, and enhancing exercise self-efficacy were important components of programs. Social support was also an important enabler of women's engagement in activities. CONCLUSIONS AND RELEVANCE: Several barriers and enablers were identified and can inform practitioners and future interventions to encourage physical activity among women in various stages of menopause. For instance, when encouraging physical activity during menopause, practitioners should consider other health complaints, safety, and injury prevention while discussing the benefits of physical activity related to managing menopausal symptoms. There was a lack of theoretically informed studies exploring the barriers and enablers to physical activity for women in various stages of menopause; thus, research designs may not have fully accounted for influences. Future research that combines socioecological and individual theories of behavior is needed to comprehensively understand the complexity of physical activity among women across the menopausal transition.
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Ejercicio Físico , Menopausia , Humanos , Femenino , Ejercicio Físico/fisiología , Menopausia/fisiología , Apoyo Social , Salud de la Mujer , Persona de Mediana Edad , AutoeficaciaRESUMEN
BACKGROUND: Cardiac distress may be viewed as a persistent negative emotional state that spans multiple psychosocial domains and challenges a patient's capacity to cope with living with their heart condition. The Cardiac Distress Inventory (CDI) is a disease-specific clinical assessment tool that captures the complexity of this distress. In busy settings such as primary care, cardiac rehabilitation, and counselling services, however, there is a need to administer briefer tools to aid in identification and screening. The aim of the present study was to develop a short, valid screening version of the CDI. METHODS: A total of 405 participants reporting an acute coronary event in the previous 12 months was recruited from three hospitals, through social media and by direct enrolment on the study website. Participants completed an online survey which included the full version of the CDI and general distress measures including the Kessler K6, Patient Health Questionnaire-4, and Emotion Thermometers. Relationship of the CDI with these instruments, Rasch analysis model fit and clinical expertise were all used to select items for the short form (CDI-SF). Construct validity and receiver operating characteristics in relation to the Kessler K6 were examined. RESULTS: The final 12 item CDI-SF exhibited excellent internal consistency indicative of unidimensionality and good convergent and discriminant validity in comparison to clinical status measures, all indicative of good construct validity. Using the K6 validated cutoff of ≥ 18 as the reference variable, the CDI-SF had a very high Area Under the Curve (AUC) (AUC = 0.913 (95% CI: 0.88 to 0.94). A CDI-SF score of ≥ 13 was found to indicate general cardiac distress which may warrant further investigation using the original CDI. CONCLUSION: The psychometric findings detailed here indicate that the CDI-SF provides a brief psychometrically sound screening measure indicative of general cardiac distress, that can be used in both clinical and research settings.
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Rehabilitación Cardiaca , Humanos , Área Bajo la Curva , Emociones , Corazón , HospitalesRESUMEN
BACKGROUND: Many challenges are posed by the experience of a heart attack or heart surgery which can be characterised as 'cardiac distress'. It spans multiple psychosocial domains incorporating patients' responses to physical, affective, cognitive, behavioural and social symptoms and experiences related to their cardiac event and their recovery. Although some measures of the psychological and emotional impacts of a cardiac event exist, none provides a comprehensive assessment of cardiac distress. To address this gap, the study aimed to develop a Cardiac Distress Inventory (CDI) using best practice in instrument design. METHOD: An item pool was generated through analysis of cognate measures, mostly in relation to other health conditions and through focus group and individual review by a multidisciplinary development team, cardiac patients, and end-users including cardiac rehabilitation co-ordinators. The resulting 144 items were reduced through further reviews to 74 for testing. The testing was carried out with 405 people recruited from three hospitals, through social media and by direct enrolment on the study website. A two-stage psychometric evaluation of the 74 items used exploratory factor analysis to extract the factors followed by Rasch analysis to confirm dimensionality within factors. RESULTS: Psychometric analysis resulted in the identification of 55 items comprising eight subscales, to form the CDI. The subscales assess fear and uncertainty, disconnection and hopelessness, changes to roles and relationships, overwhelm and depletion, cognitive challenges, physical challenges, health system challenges, and death concerns. Validation against the Kessler 6 supports the criterion validity of the CDI. CONCLUSION: The CDI reflects a nuanced understanding of cardiac distress and should prove to be a useful clinical assessment tool, as well as a research instrument. Individual subscales or the complete CDI could be used to assess or monitor specific areas of distress in clinical practice. Development of a short form screening version for use in primary care, cardiac rehabilitation and counselling services is warranted.
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Estrés Psicológico , Humanos , Encuestas y Cuestionarios , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicología , Psicometría , Reproducibilidad de los ResultadosRESUMEN
In research spanning three decades we have estimated brain monoamine turnover (approximately equating with synthesis rate) with sampling from the internal jugular veins and measurement of trans-cerebral plasma monoamine metabolite concentration gradients. Here we report indices of brain noradrenaline and serotonin turnover in patients with major depressive illness (MDD) and panic disorder (PD). Brain noradrenaline turnover was assessed from the combined flux into the internal jugular veins of the metabolites dihydroxyphenylglycol (DHPG) and 3-hydroxy-4-methoxyphenylglycol (MHPG), and brain serotonin turnover from the overflow of the primary metabolite, 5-hydroxyindole acetic acid (5HIAA). Comparison was made with matched healthy research participants. In both MD and PD the estimate of brain noradrenaline turnover provided by metabolite overflow was unremarkable. In contrast, in both patient groups the estimate of brain serotonin turnover provided by 5HIAA overflow was increased 3-4-fold (P < 0.01). This neurotransmitter abnormality was normalized in MDD and PD in clinical remission, during selective serotonin reuptake blocker (SSRI) dosing. We cannot be sure if the brain serotonergic abnormality we find in MDD and PD is causal or a correlate. Measurements in PD were not made during a panic attack. The increased estimated serotonin turnover here may possibly be a substrate for panic attacks; serotonergic raphe nuclei participate in anxiety responses in experimental animals. It is puzzling that the findings were identical in MDD and PD, although it may be pertinent that these psychiatric diagnoses are commonly comorbid. It is unlikely that activation of brain serotonergic neurons is driving the sympathetic nervous activation present, which contributes to cardiovascular risk, persistent sympathetic activation in MDD and episodic activation in PD during panic attacks. We have previously demonstrated that the mechanism of activation of human central sympathetic outflow in other contexts (hypertension, heart failure) is activation of noradrenergic brainstem neurons projecting to the hypothalamus and amygdala.
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Introduction: While much research attention has been paid to anxiety and depression in people who have had a recent cardiac event, relatively little has focused on the broader concept of cardiac distress. Cardiac distress is a multidimensional construct that incorporates but extends beyond common mood disorders such as anxiety and depression. In the present study we assessed the prevalence, severity and predictors of a broad range of physical, affective, cognitive, behavioral and social symptoms of cardiac distress. This is the first study to investigate cardiac distress in this comprehensive way. Method: A sample of 194 patients was recruited from two hospitals in Australia. Eligible participants were those who had recently been hospitalized for an acute cardiac event. Data were collected at patients' outpatient clinic appointment ~8 weeks after their hospital discharge. Using a questionnaire developed through a protocol-driven 3-step process, participants reported on whether they had experienced each of 74 issues and concerns in the past 4 weeks, and the associated level of distress. They also provided sociodemographic and medical information. Regression analyses were used to identify risk factors for elevated distress. Results: Across the 74 issues and concerns, prevalence ratings ranged from a high of 66% to a low of 6%. The most commonly endorsed items were within the domains of dealing with symptoms, fear of the future, negative affect, and social isolation. Common experiences were "being physically restricted" (66%), "lacking energy" (60%), "being short of breath" (60%), "thinking I will never be the same again" (57%), and "not sleeping well" (51%). While less prevalent, "not having access to the health care I need," "being concerned about my capacity for sexual activity," and "being unsupported by family and friends" were reported as highly distressing (74, 64, and 62%) for those experiencing these issues. Having a mental health history and current financial strain were key risk factors for elevated distress. Conclusion and Implications: Specific experiences of distress appear to be highly prevalent in people who have had a recent cardiac event. Understanding these specific fears, worries and stressors has important implications for the identification and management of post-event mental health and, in turn, for supporting patients in their post-event cardiac recovery.
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Social connections are crucial for an individual's health, wellbeing, and overall effective functioning. During the COVID-19 pandemic, one major preventative effort for reducing the spread of COVID-19 involved restricting people's typical social interactions through physical distancing and isolation. The current cross-sectional study, conducted during the COVID-19 pandemic, explored the relationship among fear of COVID-19, social connectedness, resilience, depressive symptomologies, and self-perceived stress. Participants (N = 174) completed an anonymous, online questionnaire, and results indicated that social connectedness mediated the relationship between fear of COVID-19 and psychological wellbeing. In contrast, the relationship between fear of COVID-19 and psychological wellbeing was not mediated by resilience. These findings highlight the important role that social connections and resilience play in buffering against negative psychological wellbeing outcomes, especially during a pandemic.
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AIMS: Despite its demonstrated benefits, cardiac rehabilitation (CR) attendance, and completion is suboptimal, particularly in women. The aims of this study were (i) to develop and pilot test a women-only yoga-based CR programme (the Women's Yoga CR Programme; WYCRP); (ii) to investigate programme acceptability; and (iii) to investigate attendance and completion of the WYCRP and continuation to Phase III community-based CR. METHODS AND RESULTS: Women eligible for CR at a tertiary hospital in Melbourne, Australia were recruited. Over a 6-month period in 2019, they were offered the WYCRP or usual CR. The WYCRP involved attendance at a 1-h yoga session following the usual 1-h mixed-sex education session, over a 7-week period. Participants completed pre- and post-programme questionnaires and attended focus groups to assess programme acceptability. Rates of attendance, completion, and continuation for the WYCRP were recorded and compared to those for the standard CR programme offered in 2018. In total, 27 women were eligible for the study and attended the initial CR assessment. Of those, 22 (81%) attended the WYCRP, 1 (4%) attended usual CR, and 4 (15%) did not attend CR. Ratings of programme acceptability were consistently positive; qualitative comments highlighted both physical and emotional benefits. While attendance at the WYCRP was not significantly higher than for usual CR the previous year (81% vs. 76%; P = 0.40), CR completion, and continuation were (95% vs. 56%; P = 0.02, and 72% vs. 12%; P < 0.001, respectively). CONCLUSION: This pilot study has demonstrated that women-only yoga-based CR is appealing to women and can improve women's CR completion and continuation. These preliminary findings support further development of women-only and yoga-based CR options.
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Rehabilitación Cardiaca , Yoga , Australia , Femenino , Humanos , Proyectos Piloto , Encuestas y CuestionariosRESUMEN
Unlike noradrenaline, the sympathetic neurotransmitter which overflows to the circulation, adrenaline (ADR) is a secreted hormone, with a low plasma concentration, and plasma concentration for biological action a log order lower than that of noradrenaline. The venous drainage of the left adrenal medulla into the left renal vein does expose this vein to uniquely high plasma ADR concentrations and possible risk of thrombosis at high rates of ADR secretion. There is typically a different timeframe for adrenal medullary and sympathetic nervous system responses: ADR release is short term in contrast with sympathetic activation persisting for years in heart failure and hypertension. The historic view of Walter Cannon, subject to recent review, that the sympathoadrenal system is a unified biological system, was deconstructed further with demonstration of frequent mismatching of adrenal medullary and sympathetic nervous responses. Under gravity stimulation with standing, there is prompt sympathetic activation without ADR release. In many diseases, notably obesity, hypertension, heart failure and depressive illness, an activated sympathetic nervous system and silent adrenal medulla coexist. The therapeutic corollary of this is that ADR blockade is much less commonly needed clinically than pharmacological antagonism of the sympathetic nervous system.
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Médula Suprarrenal , Hipertensión , Epinefrina , Humanos , Norepinefrina , Sistema Nervioso SimpáticoRESUMEN
INTRODUCTION: Distress is experienced by the majority of cardiac patients, yet no cardiac-specific measure of distress exists. The aim of this project is to develop and validate the Cardiac Distress Inventory (CDI). Using the CDI, health professionals will be able to identify key clusters of psychological, emotional and social concern to address with patients, postcardiac event. METHODS AND ANALYSIS: An item pool will be generated through: identification of items by a multidisciplinary group of clinician researchers; review of generic and condition-specific distress measures; focus group testing with cardiac rehabilitation professionals; feedback from patients. The COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) criteria will be used to inform the development of the methodology for determining the CDI's psychometric properties. The item pool will be tested with 400 cardiac patients and responses subjected to exploratory factor analysis, Rasch analysis, construct validity testing and latent class analysis. Receiver operating characteristic analysis will be used to identify the optimal CDI cut-off score for distinguishing whether a person experiences clinically significant distress. ETHICS AND DISSEMINATION: Approved by the Monash Health Human Research Ethics Committee (approval number-RES-19-0000631L-559790). The CDI will be made available to clinicians and researchers without charge. The CDI will be translated for use internationally. Study findings will be shared with cardiac patient support groups; academic and medical communities via publications and presentations; in the training of cardiac secondary prevention professionals; and in reports to funders. Authorship for publications will follow the uniform requirements for manuscripts submitted to biomedical journals.
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Enfermedades Cardiovasculares/psicología , Distrés Psicológico , Psicometría/instrumentación , Consenso , Emociones , Humanos , Proyectos de Investigación , Estudios de Validación como AsuntoRESUMEN
INTRODUCTION: Patients who are anxious or depressed after an acute cardiac event are at increased risk of a subsequent event and premature death. It is therefore important to identify these patients early in order to initiate supportive or even preventive measures. In the present study, we report on the prevalence of anxiety and depression during the first 12 months after an acute cardiac event, and the patient characteristics predictive of increased anxiety and depression risk in early and late convalescence. METHODS: We recruited a sample of 911 patients with acute myocardial infarction (AMI), acute coronary syndrome (ACS), and/or unstable angina (UA), and/or undergoing coronary artery bypass graft surgery (CABGS). Patients completed the Hospital Anxiety and Depression Scale (HADS) close to the time of their event, and again during early (2-4 months post-event) and late (6-12 months post-event) convalescence. Using HADS-A and HADS-D cut-offs of 8+, prevalence rates for anxiety, depression, and comorbid anxiety and depression were determined for each timepoint. Chi-square tests and odds ratios were used to identify baseline patient characteristics associated with increased anxiety and depression risk over 12 months. RESULTS: Anxiety rates were 43, 28, and 27% at the time of the event, early, and late convalescence. Depression rates were 22, 17, and 15%, respectively. Factors consistently associated with increased anxiety and depression risk were history of depression, financial strain, poor self-rated health, low socioeconomic status, younger age (<55 years), and smoking. Obesity, diabetes, and social isolation (living alone or being unpartnered) were identified as important albeit less significant risk factors. Neither sex nor event type were predictive of anxiety or depression. CONCLUSION: This large patient sample provided the opportunity to identify rates of anxiety and depression during the 12 months after a cardiac event and key patient characteristics for increased risk. These risk factors are easily identifiable at the time of the event, and could be used to guide the targeting of support programs for patients at risk.
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BACKGROUND: The relative risks and benefits of children attending kindergarten or pre-school remain uncertain and controversial. We used data from the Bavarian Pre-School Morbidity Survey (BPMS) to look at the prevalence of developmental impairments in pre-school children entering primary school and to assess if these were correlated with the duration of kindergarten attendance. METHODS: We collected data from all school beginners in the district of Dingolfing, Bavaria from 2004 to 2007 (n = 4,005) and utilised a retrospective cross-sectional study design to review the information. The children were assessed for motor, cognitive, language and psychosocial impairments using a standardized medical assessment. Point prevalence of impairments of speech, cognition, motor functioning and psychosocial functioning were compared by chi(2)-test for the variable of time spent in kindergarten. RESULTS: We detected a high incidence of impairments, with boys showing higher rates than girls in all the areas assessed. Longer length of time spent in kindergarten was associated with reduced rates of motor, cognitive and psychosocial impairments. There was no clear correlation between length of kindergarten attendance and speech disorders. CONCLUSIONS: Kindergarten attendance may have a positive effect on a number of domains of development including motor, cognitive and psychosocial development, but no significant effect on speech impairments. Implications for public health policies are discussed.
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Guarderías Infantiles , Desarrollo Infantil , Discapacidades del Desarrollo/prevención & control , Casas Cuna , Preescolar , Estudios Transversales , Femenino , Humanos , Masculino , Desempeño Psicomotor , Estudios RetrospectivosRESUMEN
AIMS: Patients with depression often have co-morbid pain symptoms. However, rates of service utilization by psychiatric in-patients with co-morbid pain symptoms are unknown. The purpose of this study is to estimate whether patients with major depression and co-morbid pain access medical treatment for their pain as much as their counterparts with psychiatric diagnoses other than major depression. METHODS: A total of 103 patients (62 female; 41 male) were assessed for a diagnosis of major depression applying a psychiatric clinical interview followed by a self-report pain questionnaire, which assessed physical pain in psychiatric patients. RESULTS: Patients with major depression reported higher rates of pain symptoms in the past 6 and 12 months than their counterparts with a psychiatric diagnosis other than major depression. Analysis of variance showed that patients with depression were less likely to attend medical and specialist services for their pain symptoms than their counterparts. On the contrary, depressed patients with pain attended more frequently general in-patient services than non-depressed patients with pain. CONCLUSIONS: Patients with depression suffer high rates of pain symptoms, but are at higher risk of not accessing appropriate services suggesting inadequate service utilization. The results have implications for screening and health care delivery for psychiatric patients with pain.
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Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/economía , Servicios de Salud/economía , Servicios de Salud/estadística & datos numéricos , Dolor/complicaciones , Dolor/economía , Adulto , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Educación , Empleo , Femenino , Alemania/epidemiología , Humanos , Pacientes Internos , Masculino , Dolor/epidemiología , Escalas de Valoración Psiquiátrica , Factores Sexuales , Encuestas y CuestionariosRESUMEN
1. In searching for biological evidence that essential hypertension is caused by chronic mental stress, a disputed proposition, parallels are noted with panic disorder, which provides an explicit clinical model of recurring stress responses. 2. There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. Plasma cortisol is elevated in both. 3. In panic disorder and essential hypertension, but not in health, single sympathetic nerve fibres commonly fire repeatedly within an individual cardiac cycle; this appears to be a signature of stress exposure. For both conditions, adrenaline cotransmission is present in sympathetic nerves. 4. Tissue nerve growth factor is increased in both (nerve growth factor is a stress reactant). There is induction of the adrenaline synthesizing enzyme, phenylethanolamine-N-methyltransferase, in sympathetic nerves, an explicit indicator of mental stress exposure. 5. The question of whether chronic mental stress causes high blood pressure, still hotly debated, has been reviewed by an Australian Government body, the Specialist Medical Review Council. Despite the challenging medicolegal implications, the Council determined that stress is one proven cause of hypertension, this ruling being published in the 27 March 2002 Australian Government Gazette. This judgement was reached after consideration of the epidemiological evidence, but in particular after review of the specific elements of the neural pathophysiology of essential hypertension, described above.
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Biomarcadores/sangre , Hipertensión/sangre , Estrés Psicológico/sangre , Humanos , Factores de TiempoRESUMEN
Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress--a disputed proposition--we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation-related inhibitory transcription factor MeCP2.
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Epigénesis Genética , Hipertensión/fisiopatología , Trastorno de Pánico/fisiopatología , Estrés Psicológico/fisiopatología , Sistema Nervioso Simpático/fisiología , Sistema Nervioso Simpático/fisiopatología , Potenciales de Acción/fisiología , Biomarcadores/análisis , Metilación de ADN , Epinefrina/metabolismo , Silenciador del Gen , Humanos , Hidrocortisona/sangre , Hipertensión/etiología , Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/metabolismo , Factor de Crecimiento Nervioso/metabolismo , Neuronas/fisiología , Norepinefrina/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Trastorno de Pánico/etiología , Feniletanolamina N-Metiltransferasa/genética , Feniletanolamina N-Metiltransferasa/metabolismo , Estrés Psicológico/complicaciones , Sistema Nervioso Simpático/anatomía & histologíaRESUMEN
Since the brain neurotransmitter changes characterising panic disorder remain uncertain, we quantified brain noradrenaline and serotonin turnover in patients with panic disorder, in the absence of a panic attack. Thirty-four untreated patients with panic disorder and 24 matched healthy volunteers were studied. A novel method utilising internal jugular venous sampling, with thermodilution measurement of jugular blood flow, was used to directly quantify brain monoamine turnover, by measuring the overflow of noradrenaline and serotonin metabolites from the brain. Radiographic depiction of brain venous sinuses allowed differential venous sampling from cortical and subcortical regions. The relation of brain serotonin turnover to serotonin transporter genotype and panic disorder severity were evaluated, and the influence of an SSRI drug, citalopram, on serotonin turnover investigated. Brain noradrenaline turnover in panic disorder patients was similar to that in healthy subjects. In contrast, brain serotonin turnover, estimated from jugular venous overflow of the metabolite, 5-hydroxyindole acetic acid, was increased approximately 4-fold in subcortical brain regions and in the cerebral cortex (P < 0.01). Serotonin turnover was highest in patients with the most severe disease, was unrelated to serotonin transporter genotype, and was reduced by citalopram (P < 0.01). Normal brain noradrenaline turnover in panic disorder patients argues against primary importance of the locus coeruleus in this condition. The marked increase in serotonin turnover, in the absence of a panic attack, possibly represents an important underlying neurotransmitter substrate for the disorder, although this point remains uncertain. Support for this interpretation comes from the direct relationship which existed between serotonin turnover and illness severity, and the finding that SSRI administration reduced serotonin turnover. Serotonin transporter genotyping suggested that increased whole brain serotonin turnover most likely derived not from impaired serotonin reuptake, but from increased firing in serotonergic midbrain raphe neurons projecting to both subcortical brain regions and the cerebral cortex.
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Encéfalo/efectos de los fármacos , Citalopram/uso terapéutico , Ácido Hidroxiindolacético/metabolismo , Trastorno de Pánico/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Serotonina/metabolismo , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Estudios de Casos y Controles , Cateterismo Venoso Central , Cateterismo Periférico , Circulación Cerebrovascular , Citalopram/farmacología , Genotipo , Humanos , Ácido Hidroxiindolacético/sangre , Metoxihidroxifenilglicol/análogos & derivados , Metoxihidroxifenilglicol/metabolismo , Persona de Mediana Edad , Norepinefrina/metabolismo , Trastorno de Pánico/sangre , Trastorno de Pánico/diagnóstico por imagen , Trastorno de Pánico/metabolismo , Trastorno de Pánico/fisiopatología , Proyectos de Investigación , Serotonina/sangre , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/farmacología , Índice de Severidad de la Enfermedad , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
OBJECTIVE: This study aimed to assess the lipid-lowering properties of omega-3 fatty acids (also known as n-3 polyunsaturated fatty acids) in a group of patients taking clozapine. METHOD: Twenty-eight persons suffering from schizophrenia or schizoaffective disorder and currently taking clozapine participated in an open-label single-arm trial. Participants received supplements of 10 g of fish oil (containing 1.8 g of eicosopentaenoic acid and 1.2 g of docosahexaenoic acid) for a period of 28 days. Plasma lipids were measured on days 0 and 28. RESULTS: This study demonstrated high rates of lipid abnormalities in the participants. Participants taking omega-3 fatty acids demonstrated a statistically significant reduction in mean serum triglyceride levels of 22%. There was an associated increase in total cholesterol (6.6%) and low-density lipoprotein cholesterol (22%). Common side-effects included fishy burps or breath, but no serious side-effects or interactions where observed. CONCLUSION: Omega-3 fatty acids may be of value in patients taking clozapine and who have elevated serum triglyceride levels. Limitations of the study, practical implications and directions for future research are discussed.
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Antipsicóticos/efectos adversos , Clozapina/efectos adversos , Ácidos Grasos Omega-3/uso terapéutico , Hiperlipidemias/inducido químicamente , Hiperlipidemias/tratamiento farmacológico , Trastornos Psicóticos/tratamiento farmacológico , Esquizofrenia/tratamiento farmacológico , Adulto , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapéutico , Colesterol/sangre , LDL-Colesterol/sangre , Clozapina/farmacocinética , Clozapina/uso terapéutico , Relación Dosis-Respuesta a Droga , Ácidos Grasos Omega-3/efectos adversos , Femenino , Humanos , Hiperlipidemias/sangre , Masculino , Persona de Mediana Edad , Trastornos Psicóticos/sangre , Esquizofrenia/sangre , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
Panic disorder can serve as a clinical model for testing whether mental stress can cause heart disease. Potential neural mechanisms of cardiac risk are the sympathetic activation during panic attacks, continuing release of adrenaline as a co-transmitter in the cardiac sympathetic nerves, and impairment of noradrenaline neuronal reuptake, augmenting sympathetic neural respnses. The phenotype of impaired neuronal reuptake of noradrenaline: an epigenetic mechanism? We suspect that this phenotype, in sensitizing people to heart symptom development, is a cause of panic disorder, and by magnifying the sympathetic neural signal in the heart, underlies increased cardiac risk. No loss of function mutations of the coding region of the norepinephrine transporter (NET) are evident, but we do detect hypermethylation of CpG islands in the NET gene promoter region. Chromatin immunoprecipitation methodology demonstrates binding of the inhibitory transcription factor, MeCP2, to promoter region DNA in panic disorder patients. Cardiovascular illnesses co-morbid with panic disorder. Panic disorder commonly coexists with essential hypertension and the postural tachycardia syndrome. In both of these cardiovascular disorders the impaired neuronal noradrenaline reuptake phenotype is also present and, as with panic disorder, is associated with NET gene promoter region DNA hypermethylation. An epigenetic 'co-morbidity' perhaps underlies the clinical concordance. Brain neurotransmitters. Using internal jugular venous sampling, in the absence of a panic attack we find normal norepinephrine turnover, but based on measurements of the overflow of the serotonin metabolite, 5HIAA, a marked increase (six to sevenfold) in brain serotonin turnover in patients with panic disorder. This appears to represent the underlying neurotransmitter substrate for the disorder. Whether this brain serotonergic activation is a prime mover, or consequential on other primary causes of panic disorder, including cardiac sensitization by faulty neuronal noradrenaline reuptake leading to cardiac symptoms and the enhanced vigilance which accompanies them, is unclear at present.