Melatonin use during pregnancy and lactation: A scoping review of human studies

Objective: The prevalence of sleep disorders during the perinatal period is high and large health administrative database surveys have shown that the use of exogenous melatonin in pregnant populations is quite common, about 4%. Much of the concern about using melatonin during pregnancy and breastfeeding stems from animal research. Thus, the objective of this article is to provide a critical review of human studies related to exogenous melatonin use during pregnancy and breastfeeding. Methods: The electronic databases Ovid, MEDLINE, Embase, and the Cochrane Library were searched using terms and keywords related to melatonin, pregnancy, and breastfeeding. Results: Fifteen studies were included in this review. Eight focused on melatonin use during pregnancy and seven focused on melatonin use during breastfeeding. There was a variety of study designs, including case reports, cohort studies, and clinical trials. There is a lack of randomized, controlled trials examining the efficacy and safety of melatonin as a treatment for sleep disorders during pregnancy or breastfeeding and, notably, insomnia was not the primary outcome measure in any of the studies included in this review. Clinical trials that used exogenous melatonin during pregnancy and breastfeeding for other clinical conditions have not suggested major safety concerns or adverse events. Conclusion: Contrary to what animal studies have suggested, evidence from clinical studies to date suggests that melatonin use during pregnancy and breastfeeding is probably safe in humans. This review further emphasizes the need for clinical studies on sleep disorders, including exogenous melatonin, during pregnancy and lactation.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic

Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. Results: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). Conclusion: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

Physician suicide demographics and the COVID-19 pandemic

Objective: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. Methods: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. Results: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). Conclusions: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

Lifestyle predictors of depression and anxiety during COVID-19: a machine learning approach

Abstract Introduction Recent research has suggested an increase in the global prevalence of psychiatric symptoms during the COVID-19 pandemic. This study aimed to assess whether lifestyle behaviors can predict the presence of depression and anxiety in the Brazilian general population, using a model developed in Spain. Methods A web survey was conducted during April-May 2020, which included the Short Multidimensional Inventory Lifestyle Evaluation (SMILE) scale, assessing lifestyle behaviors during the COVID-19 pandemic. Depression and anxiety were examined using the PHQ-2 and the GAD-7, respectively. Elastic net, random forest, and gradient tree boosting were used to develop predictive models. Each technique used a subset of the Spanish sample to train the models, which were then tested internally (vs. the remainder of the Spanish sample) and externally (vs. the full Brazilian sample), evaluating their effectiveness. Results The study sample included 22,562 individuals (19,069 from Brazil, and 3,493 from Spain). The models developed performed similarly and were equally effective in predicting depression and anxiety in both tests, with internal test AUC-ROC values of 0.85 (depression) and 0.86 (anxiety), and external test AUC-ROC values of 0.85 (depression) and 0.84 (anxiety). Meaning of life was the strongest predictor of depression, while sleep quality was the strongest predictor of anxiety during the COVID-19 epidemic. Conclusions Specific lifestyle behaviors during the early COVID-19 epidemic successfully predicted the presence of depression and anxiety in a large Brazilian sample using machine learning models developed on a Spanish sample. Targeted interventions focused on promoting healthier lifestyles are encouraged.

From anatomy to function: the role of the somatosensory cortex in emotional regulation

Since the pioneering work of Penfield and his colleagues in the 1930s, the somatosensory cortex, which is located on the postcentral gyrus, has been known for its central role in processing sensory information from various parts of the body. More recently, a converging body of literature has shown that the somatosensory cortex also plays an important role in each stage of emotional processing, including identification of emotional significance in a stimulus, generation of emotional states, and regulation of emotion. Importantly, studies conducted in individuals suffering from mental disorders associated with abnormal emotional regulation, such as major depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety and panic disorders, specific phobia, obesity, and obsessive-compulsive disorder, have found structural and functional changes in the somatosensory cortex. Common observations in the somatosensory cortices of individuals with mood disorders include alterations in gray matter volume, cortical thickness, abnormal functional connectivity with other brain regions, and changes in metabolic rates. These findings support the hypothesis that the somatosensory cortex may be a treatment target for certain mental disorders. In this review, we discuss the anatomy, connectivity, and functions of the somatosensory cortex, with a focus on its role in emotional regulation.

Salivary cortisol during memory encoding in pregnancy predicts postpartum depressive symptoms: a longitudinal study / Cortisol salivar durante aquisição de memória na gravidez prediz sintomas depressivos no período pós-parto: um estudo longitudinal

Abstract Introduction Postpartum depression (PPD) is a common disorder that substantially decreases quality of life for both mother and child. In this longitudinal study, we investigated whether emotional memory, salivary cortisol (sCORT) or alpha-amylase during pregnancy predict postpartum depressive symptoms. Methods Forty-four pregnant women (14 euthymic women with a diagnosis of major depressive disorder [MDD] and 30 healthy women) between the ages of 19 and 37 years (mean age = 29.5±4.1 years) were longitudinally assessed in the 2nd trimester of pregnancy (12-22 weeks of gestational age) and again at 14-17 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Results Follow-ups were completed for 41 women (7% attrition). Postpartum EPDS scores were predicted by sCORT collected immediately after an incidental encoding memory task during pregnancy (b=-0.78, t -2.14, p=0.04). Postpartum EPDS scores were not predicted by positive (p=0.27) or negative (p=0.85) emotional memory. Conclusions The results of this study indicate that higher levels of sCORT during a memory encoding task in the 2nd trimester of pregnancy are associated with lower postpartum EPDS scores. While the hypothalamus-pituitary-adrenal (HPA) axis has long been associated with the neurobiology of MDD, the role of the HPA axis in perinatal depression deserves more attention.

Resumo Introdução A depressão pós-parto é um transtorno prevalente que afeta negativamente a qualidade de vida da mãe e da criança. Neste estudo longitudinal, nós investigamos se a memória emocional, o cortisol salivar (salivary cortisol, sCORT) ou alfa-amilase durante a gravidez predizem sintomas depressivos no período pós-parto. Métodos Um total de 44 mulheres grávidas [14 eutímicas com diagnóstico de transtorno depressivo maior (TDM) e 30 voluntárias sadias] entre 19 e 37 anos de idade (idade média = 29.5±4.1 anos) foram avaliadas longitudinalmente no 2° trimestre da gravidez (12-22 semanas de gestação) e na 1417ª semana pós-parto. Sintomas depressivos foram avaliados com a Escala de Depressão Pós-Natal de Edimburgo (Edinburgh Postnatal Depression Scale, EPDS). Resultados Quarenta e uma mulheres completaram o seguimento (7% de perda). sCORT coletado imediatamente antes de um teste de aquisição memória durante a gravidez foi preditor dos escores da escala EPDS no período pós-parto (b=-0.78, t -2.14, p=0.04). Memória emocional positiva (p=0.27) ou negativa (p=0.85) não foram preditores dos escores da escala EPDS no período pós-parto. Conclusão Os resultados deste estudo indicam que altos níveis de sCORT durante um teste de aquisição de memória no 2° trimestre da gravidez foram associados com baixos escores na escala EPDS no período pós-parto. Uma vez que o eixo hipotálamo-hipófise-adrenal (HHA) tenha sido envolvido na neurobiologia do TDM, o papel do eixo HHA na depressão perinatal merece mais atenção.

Validation of the Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST) and association of PSST scores with health-related quality of life

Objective: To develop and validate a Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST), a questionnaire used for the screening of premenstrual syndrome (PMS) and of the most severe form of PMS, premenstrual dysphoric disorder (PMDD). The PSST also rates the impact of premenstrual symptoms on daily activities. Methods: A consecutive sample of 801 women aged ≥ 18 years completed the study protocol. The internal consistency, test-retest reliability, and content validity of the Brazilian PSST were determined. The independent association of a positive screen for PMS or PMDD and quality of life determined by the World Health Organization Quality of Life instrument-Abbreviated version (WHOQOL-Bref) was also assessed. Results: Of 801 participants, 132 (16.5%) had a positive screening for PMDD. The Brazilian PSST had adequate internal consistency (Cronbach’s alpha = 0.91) and test-retest reliability. The PSST also had adequate convergent/discriminant validity, without redundancy. Content validity ratio and content validity index were 0.61 and 0.94 respectively. Finally, a positive screen for PMS/PMDD was associated with worse WHOQOL-Bref scores. Conclusions: These findings suggest that PSST is a reliable and valid instrument to screen for PMS/PMDD in Brazilian women.

Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study

Objective: Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Methods: Thirty-three healthy pregnant women were recruited from the Women’s Health Concerns Clinic at St. Joseph’s Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Results: Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. Conclusions: Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

The Mood Rhythm Instrument: development and preliminary report

Objective: To describe the initial steps in the development and validation of a new self-reported instrument designed to assess daily rhythms of mood symptoms, namely, the Mood Rhythm Instrument. Methods: A multidisciplinary group of experts took part in systematic meetings to plan the construction of the instrument. Clarity of items, their relevance to evaluation of mood states, and the consistency of findings in relation to the available evidence on the biological basis of mood disorders were investigated. The internal consistency of the questionnaire was evaluated through Cronbach’s alpha. Results: All of the items proposed in a first version were well rated in terms of clarity. The items more frequently rated as “rhythmic” were related to the somatic symptoms of mood. Their peaks in 24 hours were more frequent in the morning. The items associated with affective symptoms of mood were rated as less rhythmic, and their peak in 24 hours occurred more frequently in the afternoon and evening. Males and females behaved more similarly with respect to somatic than behavioral-affective items. The second version of the Mood Rhythm Instrument had a Cronbach’s alpha of 0.73. Conclusion: The proposed Mood Rhythm Instrument may be able to detect individual rhythms of cognitive and behavioral measures associated with mood states. Validation in larger samples and against objective measures of rhythms, such as actigraphy, is warranted.

Mitochondrial Dysfunction in Bipolar Disorder: Lessons from Brain Imaging and Molecular Markers / Disfunción mitocondrial en el trastorno bipolar: lecciones de las imágenes cerebrales y los marcadores moleculares

Bipolar disorder (BD) is a chronic major mental illness characterized by extreme mood episodes, cognitive impairment, and high rates of disability. Several lines of evidence suggest that BD may be associated with abnormalities in mitochondrial function. Here we critically review findings from brain imaging and from preclinical studies that investigated markers of energy metabolism in BD. Research with postmortem brain and peripheral tissue revealed changes in size and distribution of mitochondria, as well as decreased mitochondrial electron transport chain function, increased oxidative stress, and increased lipid and protein damage. PET imaging studies revealed decreased glucose metabolism in sub-areas of the prefrontal cortex, amygdala, and hippocampus structures in BD. On the other hand, increased lactate levels in BD have been found in cerebrospinal fluid and in gray matter by magnetic resonance spectroscopy, which suggest that distinct pathophysiological processes may be region-specific. Resting state fMRI studies have demonstrated decreased functional connectivity between fronto-limbic circuits. In conclusion, these results support the hypothesis of mitochondrial dysfunction in BD and suggest that BD is associated with decreased energy production and a shift towards anaerobic glycolysis. Such changes in energy metabolism can potentially decrease cell plasticity and ultimately disrupt brain circuits associated with mood and cognitive control.

El trastorno bipolar (TB) es una enfermedad mental crónica grave caracterizada por episodios de ánimo extremo, trastornos cognitivos y altas tasas de discapacidad. Varias líneas de evidencia sugieren que el TB puede estar asociado con anormalidades en la función mitocondrial. Aquí analizamos críticamente los hallazgos de las imágenes cerebrales y de los estudios preclínicos que han investigado los marcadores del metabolismo de energía en TB. Las investigaciones post mórtem basadas en tejidos cerebrales y tejidos periféricos revelaron cambios en el tamaño y en la distribución de las mitocondrias, además de una disminución en la funcionalidad de la cadena de transporte de electrones de las mitocondrias, un mayor estrés oxidativo y mayores daños lipídicos y proteínicos. Estudios con imágenes TEP revelan un metabolismo de glucosa disminuido en las subáreas de la corteza prefrontal, la amígdala y el hipocampo en TB. Por otro lado, se han hallado concentraciones mayores de lactato en TB en el líquido cefalorraquídeo cerebral y en la materia gris utilizando la espectroscopia con resonancia magnética, lo cual sugiere que los procesos fisiopatológicos individuales pueden ser específicos de las distintas regiones. Los estudios con resonancias magnéticas funcionales han demostrado una menor conectividad funcional entre los circuitos frontolímbicos. En conclusión, estos resultados apoyan la hipótesis de una disfunción mitocondrial en el TB y sugieren que el TB está asociado con una menor producción de energía y un cambio hacia la glicólisis anaeróbica. Estos cambios en el metabolismo energético pueden disminuir potencialmente la plasticidad celular y, en últimas, perturbar los circuitos cerebrales asociados con el estado de ánimo y el control cognitivo.

Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes / Aumento do estresse oxidativo como um mecanismo para a diminuição dos níveis de BDNF em episódios maníacos agudos

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

OBJETIVO E MÉTODO: Existem crescentes evidências indicando que alterações no fator neurotrófico derivado do cérebro e aumento do estresse oxidativo podem estar envolvidos na fisiopatologia do transtorno bipolar. Considerando os achados recentes de que os níveis de fator neurotrófico derivado do cérebro estão diminuídos em situações de aumento de estresse oxidativo, nós testamos a correlação entre os níveis séricos de substâncias reativas do ácido tiobarbitúrico, um índice de peroxidação lipídica, e os níveis séricos de fator neurotrófico derivado do cérebro em pacientes portadores de transtorno bipolar durante mania aguda e em controles saudáveis. RESULTADOS: Os níveis séricos de substâncias reativas do ácido tiobarbitúrico e fator neurotrófico derivado do cérebro apresentaram uma correlação negativa em pacientes bipolares (r = -0,56; p = 0,001), enquanto não houve correlação significativa no grupo controle. CONCLUSÃO: Estes resultados sugerem que alterações de estresse oxidativo podem ser mecanisticamente associadas com níveis reduzidos de BDNF observados em indivíduos com transtorno bipolar.

Diferentes apresentações clínico-radiológicas da pneumonia por Mycoplasma pneumoniae / Mycoplasma penumoniae pneumonia: clinical and radiological features

Objetivo: Alertar sobre a grande variabilidade das manifestações clínicas e achados radiológicos das pneumonias por Mycoplasma pneumoniae na população pediátrica. Embora referida como uma entidade prevalente nesta faixa etária, muitas vezes têm o seu diagnóstico retardado em função da ausência de um padrão que possa ser considerado realmente clássico. Métodos: Os autores apresentam 5 casos de pneumonia por este agente em faixa etária pediátrica. Discutem a dificuldades diaagnósticas, as manifestações clínicas, os achados radiológicos e a evolução após a instituição da terapêutica. Os casos têm suas peculiaridades significativas confrontados com achados da literatura médica nos últimos 20 anos, obtidos através de uma pesquisa bibliográfica realizada no banco de dados da Medline acerca do tema. Resultados: Os 5 casos siituavam-se numa faixa etária entre 6 e 9 anos, caractisticamente de maior prevalência para o aparecimento da infecção. Em nenhum dos casos a possibilidade de infecção por mycoplasma foi considerada no manejo inicial. Pneumonia sinuso-aspirativa, tuberculose, asma brônquica de difícil controle estiveram entre as hipóteses diagnóticas inicialmente consideradas e posteriormente descartadas. À exceção de um, todos os outros casos referiram uso de antiboticoterapia prévia. Os achados radiológicos iniciais mais chamativos foram diferentes entre todo os casos apresentados: consolidações broncopneumônicas associadas à sinais de bronquite, consolidações broncopneumônicas grosseiras, efusão pleural paraneumônica, infiltrado intersticial com adenopatia para-hilar, consolidações broncopneumônicas com componente atelectásio. Após a instituição da terapêutica específica, a evolução foi favorável em todos os casos (clínica e radiologicamente). Conclusões: A penumonia por Mycoplasma pneumoniae constitui-se numa doença com formas de manifestações clínica bastante variável. Da mesma maneira, a investigação radiológica complementar pode exigir variados padrões de apresentação. Isso faz com que, mesmo sendo uma doença prevalente na faixa etária pediátrica, nem sempre seja primariamente considerada, levanddo a um retardo no seu diagnóstico e na instituição de uma terapêutica apropriada