Targeted Analysis of Plasma Polar Metabolites in Postmenopausal Depression.

Depression will be the disease with the highest incidence worldwide by 2030. Data indicate that postmenopausal women have a higher incidence of mood disorders, and this high vulnerability seems to be related to hormonal changes and weight gain. Although research evaluating the profile of metabolites in mood disorders is advancing, further research, maintaining consistent methodology, is necessary to reach a consensus. Therefore, the objective of the present study was to carry out an exploratory analysis of the plasma polar metabolites of pre- and postmenopausal women to explore whether the profile is affected by depression. The plasma analysis of 50 polar metabolites was carried out in a total of 67 postmenopausal women, aged between 50 and 65 years, either without depression (n = 25) or with depression symptoms (n = 42), which had spontaneous onset of menopause and were not in use of hormone replacement therapy, insulin, or antidepressants; and in 42 healthy premenopausal women (21 without depression and 21 with depression symptoms), aged between 40 and 50 years and who were not in use of contraceptives, insulin, or antidepressants. Ten metabolites were significantly affected by depression symptoms postmenopause, including adenosine (FDR = 3.778 × 10-14), guanosine (FDR = 3.001 × 10-14), proline (FDR = 1.430 × 10-6), citrulline (FDR = 0.0001), lysine (FDR = 0.0004), and carnitine (FDR = 0.0331), which were down-regulated, and dimethylglycine (FDR = 0.0022), glutathione (FDR = 0.0048), creatine (FDR = 0.0286), and methionine (FDR = 0.0484) that were up-regulated. In premenopausal women with depression, oxidized glutathione (FDR = 0.0137) was down-regulated, and dimethylglycine (FDR = 0.0406) and 4-hydroxyproline (FDR = 0.0433) were up-regulated. The present study provided new data concerning the consequences of depression on plasma polar metabolites before and after the establishment of menopause. The results demonstrated that the postmenopausal condition presented more alterations than the premenopausal period and may indicate future measures to treat the disturbances involved in both menopause and depression.

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders.

The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders / O eixo microbiota-intestino-cérebro no tratamento de desordens neurológicas e psiquiátricas

Abstract The human gut microbiota is a complex ecosystem made of trillions of microorganisms. The composition can be affected by diet, metabolism, age, geography, stress, seasons, temperature, sleep, and medications. The increasing evidence about the existence of a close and bi-directional correlation between the gut microbiota and the brain indicates that intestinal imbalance may play a vital role in the development, function, and disorders of the central nervous system. The mechanisms of interaction between the gut-microbiota on neuronal activity are widely discussed. Several potential pathways are involved with the brain-gut-microbiota axis, including the vagus nerve, endocrine, immune, and biochemical pathways. Gut dysbiosis has been linked to neurological disorders in different ways that involve activation of the hypothalamic-pituitary-adrenal axis, imbalance in neurotransmitter release, systemic inflammation, and increase in the permeability of the intestinal and the blood-brain barrier. Mental and neurological diseases have become more prevalent during the coronavirus disease 2019pandemic and are an essential issue in public health globally. Understanding the importance of diagnosing, preventing, and treating dysbiosis is critical because gut microbial imbalance is a significant risk factor for these disorders. This review summarizes evidence demonstrating the influence of gut dysbiosis on mental and neurological disorders.

Resumo A microbiota intestinal humana é um ecossistema complexo feito de trilhões de microrganismos, cuja composição pode ser afetada pela dieta, pelo metabolismo, pela idade, geografia, pelo estresse, pelas estações do ano, pela temperatura, pelo sono e por medicamentos. A crescente evidência sobre a existência de uma correlação estreita e bidirecional entre a microbiota intestinal e o cérebro indica que o desequilíbrio intestinal pode desempenhar um papel vital no desenvolvimento, na função e nos distúrbios do sistema nervoso central. Os mecanismos de interação entre a microbiota intestinal e a atividade neuronal são amplamente discutidos. Várias vias potenciais estão envolvidas com o eixo microbiota-intestino-cérebro, incluindo o nervo vago e as vias endócrinas, imunes e bioquímicas. A disbiose intestinal tem sido associada a distúrbios neurológicos de diferentes maneiras que envolvem a ativação do eixo hipotálamo-hipófise-adrenal, o desequilíbrio na liberação de neurotransmissores, a inflamação sistêmica e o aumento da permeabilidade das barreiras intestinal e hematoencefálica. As doenças mentais e neurológicas tornaram-se mais prevalentes durante a pandemia de coronavirus disease 2019 e são uma questão global essencial na saúde pública. Compreender a importância de diagnosticar, prevenir e tratar a disbiose é fundamental porque o desequilíbrio microbiano intestinal é um fator de risco significativo para esses distúrbios. Esta revisão resume as evidências que demonstram a influência da disbiose intestinal em distúrbios mentais e neurológicos.

Narcolepsy: the impact of aging, hypocretin deficiency, and years of formal education in olfactory function and abdominal obesity.

BACKGROUND: Narcolepsy is a disease resulting from the loss of hypocretin-producing cells or other dysfunctions of the hypocretinergic system. In addition to sleep disorders, affected patients may experience increased weight gain, olfactory changes, and poorer quality of life. METHODS: This study aimed to investigate the relationship between narcolepsy and weight gain, years of study, sleep parameters, and olfactory dysfunction in patients with narcolepsy type 1 and narcolepsy type 2. Anthropometric, olfactory, socioeducational, and excessive daytime sleepiness evaluations were performed in 77 patients. RESULTS: Greater weight gain and abdominal obesity were observed in patients with type 1 narcolepsy. Patients with higher education level had lower scores of daytime sleepiness, higher scores on the olfactory function test, and lower rates of abdominal obesity. DISCUSSION: Patients with narcolepsy type 1 showed an increased body weight and abdominal obesity when compared to narcolepsy type 2. The patients with a higher schooling level showed a reduction of the daytime sleepiness scores, lower rates of abdominal obesity, and better scores on the olfactory function test. CONCLUSION: Among all the patients with narcolepsy, the data indicated that aging and hypocretin deficiency are associated with abdominal obesity, while years of study is the variable that mostly influences olfaction function.

Narcolepsy: the impact of aging, hypocretin deficiency, and years of formal education in olfactory function and abdominal obesity / Narcolepsia: o impacto da idade, deficiência de hipocretina e anos de estudo na função olfatória e na obesidade central

ABSTRACT Background: Narcolepsy is a disease resulting from the loss of hypocretin-producing cells or other dysfunctions of the hypocretinergic system. In addition to sleep disorders, affected patients may experience increased weight gain, olfactory changes, and poorer quality of life. Methods: This study aimed to investigate the relationship between narcolepsy and weight gain, years of study, sleep parameters, and olfactory dysfunction in patients with narcolepsy type 1 and narcolepsy type 2. Anthropometric, olfactory, socioeducational, and excessive daytime sleepiness evaluations were performed in 77 patients. Results: Greater weight gain and abdominal obesity were observed in patients with type 1 narcolepsy. Patients with higher education level had lower scores of daytime sleepiness, higher scores on the olfactory function test, and lower rates of abdominal obesity. Discussion: Patients with narcolepsy type 1 showed an increased body weight and abdominal obesity when compared to narcolepsy type 2. The patients with a higher schooling level showed a reduction of the daytime sleepiness scores, lower rates of abdominal obesity, and better scores on the olfactory function test. Conclusion: Among all the patients with narcolepsy, the data indicated that aging and hypocretin deficiency are associated with abdominal obesity, while years of study is the variable that mostly influences olfaction function.

RESUMO Antecedentes: A narcolepsia é resultante da perda de células produtoras de hipocretina ou da disfunção do sistema hipocretinérgico. Além dos distúrbios do sono característicos da doença, os pacientes afetados podem apresentar também aumento de peso, alterações olfatórias e pior qualidade de vida. Métodos: O objetivo do estudo é investigar a relação entre a narcolepsia e o ganho de peso, anos de estudo, parâmetros do sono e a disfunção olfatória em pacientes com narcolepsia tipo 1 e narcolepsia tipo 2. Foram realizadas avaliações antropométricas, do olfato, sociais, educacionais e da sonolência excessiva diurna nos 77 indivíduos participantes da pesquisa. Resultados: Foram observados, nos pacientes com narcolepsia tipo 1, maior ganho de peso e maior frequência de obesidade central. Pacientes com ensino superior apresentaram escores mais baixos de sonolência excessiva diurna, escores mais altos no teste de função olfatória e menores taxas de obesidade central. Discussão: Pacientes com narcolepsia tipo 1 apresentaram maior ganho de peso e obesidade central quando comparados aos com narcolepsia tipo 2. Os pacientes com maior escolaridade apresentaram menores escores de sonolência diurna, de obesidade central e melhores escores no teste da função olfatória. Conclusão: Nos indivíduos com narcolepsia tipo 1 e tipo 2, os dados indicaram que o envelhecimento e a deficiência de hipocretina estão associados à obesidade central, enquanto anos de estudo é a variável que mais influencia na função olfatória.

Preliminary evidence of acylated ghrelin association with depression severity in postmenopausal women.

We have previously shown increased depression and anxiety scores in postmenopausal overweight women, when compared to overweight premenopausal women. The mechanisms responsible for these alterations are not understood. Although ghrelin involvement in mood modulation has been suggested, its role is still ambiguous and has not been evaluated in postmenopause. Here we investigated the association of ghrelin with depression and anxiety symptoms in postmenopausal women. Fifty-five postmenopausal women with depression symptoms, who were not in use of hormones or antidepressants, were included in the study. Depression symptoms were evaluated by Beck's Depression Inventory (BDI) and Patient Health Questionnaire-9 (PHQ-9) and anxiety symptoms were evaluated by Beck's Anxiety Inventory (BAI). Women were allocated into three groups, according to BDI classification of mild, moderate, or severe depression symptoms. Anthropometric, biochemical and hormonal parameters were analyzed. Total and acylated ghrelin levels were higher in the severe depression than in the mild depression group. Multivariate regression analyses showed positive associations of BDI scores with acylated ghrelin and BMI, and of PHQ-9 scores with acylated ghrelin and homeostasis model assessment of insulin resistance (HOMA-IR). BAI scores associated positively with waist-to-hip ratio. To the best of our knowledge, this is the first demonstration of an association between acylated ghrelin and the severity of depression symptoms in postmenopausal women. This association may reflect either a physiological response aimed at fighting against depression symptoms or a causal factor of this mental disorder.

The influence of narcolepsy on olfactory function: a review.

INTRODUCTION: Narcolepsy is a sleep disorder associated with loss of hypocretin cells characterized by irrepressible need to sleep, often accompanied by cataplexy, sleep fragmentation, hypnagogical and hypnopompic hallucinations, and sleep paralysis. It is also correlated with alterations in the sleep-wake cycle, dysautonomia, olfactory dysfunction, and eating disorders. METHODS: This is a review about influence of narcolepsy on human olfaction. Pubmed, Embase, Ovid and Cochrane databases were searched for articles on the evaluation of olfactory function in narcoleptic patients including terms as narcolepsy, olfaction disorder, amongst others. RESULTS: Seven articles met the inclusion criteria. In five of them, the olfaction of narcoleptic patients was diminished in comparison with healthy control groups. The diagnosis of narcolepsy relates to worse performance in olfactory tests. Experimental researches showed that hypocretin and hypocretin receptors are present in the olfactory system, and this neuropeptide may have a role on olfactory sensitivity and on the olfactory modulation. The cause of hyposmia appears to be multifactorial. Among them, it stands out the hypocretin deficiency, therefore, that seems to be involved in the olfactory impairment in narcoleptic patients.

Influence of Dietary Sources of Melatonin on Sleep Quality: A Review.

Sleep is an essential biological phenomenon, being a physiological and behavioral process necessary for quality of life. Melatonin is a circadian hormone produced at night by the pineal gland, regulated by the light/dark cycle, under the control of the suprachiasmatic nucleus. Melatonin is an indoleamine, synthesized from the essential amino acid tryptophan via serotonin. Melatonin is also found in plants, where it helps fight oxidative stress. To present a systematic review on the ability of food sources of melatonin to promote healthy sleep. A literature search was performed on the PubMed, Scopus, and ScienceDirect databases, including only randomized, placebo-controlled trials published in English between 2005 and 2019. The methodological quality of the trials was assessed by the Jadad scale. Of the 25 eligible articles, eight met the inclusion criteria. They addressed the intake of milk or cherry juice in children, adults, and elderly subjects and evaluated sleep quality by questionnaires, sleep diary, actigraphy, or polysomnography. The analysis of the studies presented limitations, including lack of homogeneity of treatment dosage and duration. Nonetheless, the results indicated that the consumption of milk and sour cherries, sources of melatonin, may improve sleep quality in humans. These results pointed out to the potential suitability of food sources of melatonin as adjuvants in the prevention and treatment of sleep disorders. Further studies are necessary to better ascertain the aspects relevant to their use.

Age and leptinemia association with anxiety and depression symptoms in overweight middle-aged women.

OBJECTIVE: The aim of the study was to investigate the effect of menopause and of postmenopausal stages on depression and anxiety symptoms, and whether these symptoms associate with anthropometric, metabolic, and hormonal parameters in midlife women. METHODS: Postmenopausal women (age 50-65), either at early (EPM, n=33) or late (LPM, n = 23) postmenopause, and 23 premenopausal controls (PreM, age 40-50), matched for BMI with the PM groups, were studied. Blood biochemical and hormonal determinations, bioimpedance anthropometry, and depression and anxiety symptoms (Beck's depression [BDI] and anxiety [BAI] inventories) were conducted. RESULTS: The BAI score was higher in both PM groups than in the PreM group. In contrast, only the LPM group showed a significantly elevated BDI score. All groups presented overweight and abdominal obesity, having similar BMI and waist/hip ratio values. Both PM groups showed insulin resistance, whereas only the LPM group presented decreased skeletal muscle mass and basal metabolic rate. Correlation analysis, including all 79 middle-aged women, showed age, percentage body fat, waist/hip ratio, and leptinemia to correlate positively with the anxiety and depression scores. Multivariate regression showed leptin and age to associate positively with depressive- and anxious-like symptoms. CONCLUSIONS: Postmenopausal women presented impaired body composition, energy expenditure, insulin sensitivity, and mental symptoms, in comparison to similarly overweight premenopausal women. Among all the overweight midlife women, these symptoms were more strongly associated with age and leptin levels than with reproductive aging itself. The data indicate that, among overweight middle-aged women with abdominal obesity, the aging process and the development of leptin resistance are associated with impairment of mental health.

Association between obesity and sleep disorders in postmenopausal women.

OBJECTIVE: To investigate the relationship between obesity and sleep architecture in postmenopausal women. METHODS: One hundred seven postmenopausal women from the Ambulatory of Integrative Treatment for Female Sleep Disorders were invited by telephone to participate in this study. Fifty-three completed the study. We included women aged 50 to 70 years, and excluded women on hormone therapy or missing data. The study consisted of two meetings, including a full-night polysomnography. Menopause status was confirmed by amenorrhea for at least 1 year. Anthropometric measurements included: body mass, height, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), and neck circumference. Participants were allocated into two groups according to BMI: nonobese group (BMI <30 kg/m) and obese group (BMI ≥30 kg/m). RESULTS: The obese group had significantly (P < 0.01) increased values of BMI, neck circumference, waist circumference, and hip circumference. WHR was similar between the groups (P = 0.77). Obese participants had significantly increased values of respiratory disturbance index (16.4 vs 9.3 n°/h) and apnea-hypopnea index (14.2 vs 5.6 n°/h). Rapid eye movement sleep latency was positively correlated to body mass (r = P < 0.01), BMI (P < 0.01), and hip circumference (P = 0.01). WHR was negatively correlated to sleep efficiency (P = 0.03). The linear regression model showed that BMI (P < 0.01) and WHR (P < 0.01) were positive predictors of rapid eye movement sleep latency. CONCLUSION: In postmenopausal women, high BMI and abdominal obesity are sources of sleep disturbances, decreasing deep sleep, and sleep efficiency, while increasing the risk of obstructive sleep apnea.

Women's Sleep Disorders: Integrative Care.

The integrative care model is rooted in a biopsychosocial approach. Integrative is a term which refers to increasing the harmony and coherence of your whole being, and integrative care is therefore focused on the person, not on either the disease or a therapy. It is provided collaboratively by a health team comprising physicians, psychologists, physiotherapists, acupuncturists, and meditation, nutrition, and floral therapy. Previous studies have demonstrated that interventions based on the integrative care model improved womens lifestyle and quality of life. Our aim was to describe the use of complementary and alternative medicine (CAM) alongside traditional medicine among women with sleep conditions in our Womens Sleep Disorders Integrative Treatment Outpatient Clinic. We are sharing our experiences and clinical practice as the model we developed seems to have both physical and psychological benefits for women with sleep problems. We discuss the wide range of benefits that result from this type of complex intervention, and the contextual factors that may influence these benefits. This will inform future practitioners and we hope to contribute to quantitative research in the clinical setting. The study highlights the importance of treating sleep complaints with a caring relationship and a CAM approach, alongside conventional medicine. Exploration of the lived experience of CAM and its meaning enables healthcare professionals to gain insights into the patients needs, preferences, and values. Gynecologists, clinicians, and health care providers should support and guide patients in their decision to use CAM by providing evidence-based and comprehensive advice on the potential benefits, risks and related safety issues of this approach.

Plasma levels of acylated and total ghrelin in pediatric patients with chronic kidney disease.

This cross-sectional study set out to compare total and acyl ghrelin levels in children with mild chronic kidney disease (CKD) undergoing conservative treatment (n = 19) with children with end-stage renal disease (ESRD) undergoing hemodialysis (n = 24), and with healthy controls (n = 20). The relationship between ghrelin levels and parameters of renal function, nutritional status, and selective hormones were investigated. ESRD patients had higher total ghrelin levels than those with mild CKD or control individuals. However, acyl ghrelin did not differ between groups, indicating that the excess circulating ghrelin was desacylated. Since desacyl ghrelin has been shown to inhibit appetite, increased levels might contribute to protein-energy wasting in pediatric renal patients. When all 43 renal patients were combined, multiple regression analysis found age and glomerular filtration rate (GFR) to be significant negative predictors of total ghrelin. Acyl ghrelin was influenced negatively by age and positively by energy intake. Acyl to total ghrelin ratio related positively to GFR and energy intake. The results indicate that total but not acyl ghrelin is influenced by low GFR in children with CKD and suggests that ghrelin activation may be impaired in these patients. Since energy intake is a positive predictor of acyl ghrelin, the physiological control of ghrelin secretion appears to be altered in pediatric renal patients.