Long-term stability of respiratory sinus arrhythmia among adults with and without a history of depression.

Respiratory sinus arrhythmia (RSA) is an index of parasympathetic nervous system activity reflecting respiratory influences on heart rate. This influence is typically measured as high frequency heart rate variability (HF-HRV) or root mean square of successive differences (RMSSD) of adjacent inter-beat intervals. Examining the long-term stability of its measurement is important as levels of resting RSA have been conceptualized as a marker of individual differences; in particular, of an individual's autonomic regulation and affect-related processes, including emotion regulation. At present, it is not known if resting RSA levels reflect stable differences over a long-term period (i.e., >1 year). Even less is known about how RSA stability differs as a function of depression history and whether it relates to depression risk trajectories. In the present study, we examined the 1.5-year test-retest reliability of resting RSA using the intraclass correlation coefficient (ICC) in 82 adults: n = 41 with a history of depression (ever-depressed); n = 41 controls with no depression history (never-depressed). HF-HRV was fairly stable in both groups (ever-depressed ICC = 0.55, never-depressed ICC = 0.54). RMSSD was also fairly stable in ever-depressed adults (ICC = 0.57) and never-depressed controls (ICC = 0.40). ICC values for both indices did not differ between groups per overlapping 95% confidence intervals. Therefore, RSA stability as assessed by both frequency (HF-HRV) and time domain (RMSSD) measures was not attenuated by a depression history. Implications and the need for future research are discussed.

A commentary on "Don't mind the gap: Why we do not care about the gender gap in mental health?" by P. Patalay and O. Demkowicz.

In their article, Drs. Patalay and Demkowicz raise important questions about research regarding the sex/gender gap in depression rates. However, their perspective on this topic is rather polarizing and yields statements of questionable accuracy. In this Commentary, I respond to several statements in the Article, which I consider potentially misleading. My goal is to present a broader perspective on sex/gender and depression and encourage further discussion of this important topic.

Effects of current and past depressive episodes on behavioral performance and subjective experience during an N-back task.

BACKGROUND AND OBJECTIVES: Depression impairs working memory (WM). And, while many studies have documented impairment in WM during depression remission, those using the N-back task did not find differences between individuals with remitted depression and healthy controls. One reason for these findings may be that certain depression phenotypes, such as the childhood-onset form, which is likely to be associated with persistent WM problems, are underrepresented or unevenly represented in the studies. Because childhood-onset depression (COD) affects individuals while cognitive development is still ongoing, it is more likely to have lasting detrimental effects, as evidenced in residual memory impairment, than depression that onsets later in life. Further, it is unclear if depression episodes have cumulative effects on WM when measured via the N-back. METHODS: We examined the effects of depression on WM performance (response time, accuracy, signal detection d') and subjective experience (difficulty, mental effort required) during a four-level N-back task among 112 adults with COD (42 currently depressed; 70 remitted depressed) and 80 never-depressed controls. RESULTS: Compared to never-depressed controls, there was minimal evidence of impaired WM performance among participants with remitted or current depression; the groups also reported overall similar subjective experiences during the N-back. Notably, number of lifetime depressive episodes had a detrimental cumulative effect on response accuracy and d'. LIMITATIONS: WM was assessed only in regard to verbal memory. The sample size of currently depressed cases was smaller than that of the other groups. CONCLUSIONS: WM remains largely intact among adults with remitted COD, but increased number of depression episodes worsens WM performance.

History of major depressive disorder is associated with differences in implicit learning of emotional faces.

Major depressive disorder is often associated with worsened reward learning, with blunted reward response persisting after remission. In this study, we developed a probabilistic learning task with social rewards as a learning signal. We examined the impacts of depression on social rewards (facial affect displays) as an implicit learning signal. Fifty-seven participants without a history of depression and sixty-two participants with a history of depression (current or remitted) completed a structured clinical interview and an implicit learning task with social reward. Participants underwent an open-ended interview to evaluate whether they knew the rule consciously. Linear mixed effects models revealed that participants without a history of depression learned faster and showed a stronger preference towards the positive than the negative stimulus when compared to the participants with a history of depression. In contrast, those with a history depression learned slower on average and displayed greater variability in stimulus preference. We did not detect any differences in learning between those with current and remitted depression. The results indicate that on a probabilistic social reward task, people with a history of depression exhibit slower reward learning and greater variability in their learning behavior. Improving our understanding of alterations in social reward learning and their associations with depression and anhedonia may help to develop translatable psychotherapeutic approaches for modification of maladaptive emotion regulation.

Economic Choice and Heart Rate Fractal Scaling Indicate That Cognitive Effort Is Reduced by Depression and Boosted by Sad Mood.

BACKGROUND: People with depression typically exhibit diminished cognitive control. Control is subjectively costly, prompting speculation that control deficits reflect reduced cognitive effort. Evidence that people with depression exert less cognitive effort is mixed, however, and motivation may depend on state affect. METHODS: We used a cognitive effort discounting task to measure propensity to expend cognitive effort and fractal structure in the temporal dynamics of interbeat intervals to assess on-task effort exertion for 49 healthy control subjects, 36 people with current depression, and 67 people with remitted depression. RESULTS: People with depression discounted more steeply, indicating that they were less willing to exert cognitive effort than people with remitted depression and never-depressed control subjects. Also, steeper discounting predicted worse functioning in daily life. Surprisingly, a sad mood induction selectively boosted motivation among participants with depression, erasing differences between them and control subjects. During task performance, depressed participants with the lowest cognitive motivation showed blunted autonomic reactivity as a function of load. CONCLUSIONS: Discounting patterns supported the hypothesis that people with current depression would be less willing to exert cognitive effort, and steeper discounting predicted lower global functioning in daily life. Heart rate fractal scaling proved to be a highly sensitive index of cognitive load, and data implied that people with lower motivation for cognitive effort had a diminished physiological capacity to respond to rising cognitive demands. State affect appeared to influence motivation among people with current depression given that they were more willing to exert cognitive effort following a sad mood induction.

Metabolic syndrome among young adults at high and low familial risk for depression.

BACKGROUND: Our study examined whether the early-onset depression phenotype among young adults (probands) is associated with the metabolic syndrome (MetS) and its components, and if MetS characterizes unaffected but high-risk siblings of probands. METHODS: We studied three groups of young adults (Mage = 25 years, s.d. = 3.84 years): probands with histories of childhood onset depression - i.e. early-onset phenotype - (n = 293), their unaffected siblings (high-risk siblings, n = 273), and healthy controls (n = 171). Participants completed a full psychiatric interview, physical and laboratory assessments, and self-rating scales. MetS was defined using the criteria of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (). RESULTS: Early-onset depression phenotype and being a high-risk sibling were associated with higher MetS composite scores relative to that of controls, but did not differ from one another. With regard to MetS components: Probands and siblings had similarly larger waist circumference and lower HDL than did controls, while siblings and controls had lower triglyceride levels than did probands but did not differ from one another. Groups did not differ on glucose levels and SBP. CONCLUSIONS: Our study extends the literature on the association between MetS and depression and underscores the importance of depression phenotypes: failure to account for the clinical heterogeneity of depression may partly underlie the inconsistent findings regarding its relation to MetS. The results also suggest that, in depression-prone populations, MetS may predate and possibly function as a risk factor for eventual depression.

Comprehension and Decision-Making Capacity Questionnaire About Palliative Care and Advance Care Planning: A Delphi Study.

Objective(s): To develop a questionnaire that assesses the level of comprehension and decision-making capacity of patients with breast cancer about palliative care and advance care planning. Methods: Questionnaire items were based on the scientific literature. Delphi Consensus, a three-round survey with experts (n = 14), evaluated the relevance, clarity, and redundancies of the items. A pretest with breast cancer patients (n = 15) evaluated whether they comprehended each item and identified doubts or discomforts. Results: The initial questionnaire was composed of 38 items. After the Delphi, 18 items were restructured, six were added, and 16 were removed. In the pretest phase, all items with the survey header, guidelines, and Likert model were evaluated. All items accomplished ≥80% cut-off score and were kept as in the original version. The final version of the questionnaire have 28 itens and five domains: determination, responsibility, independence, self-knowledge, and knowledge of reality. Conclusions: This study represents the first step in the development of a questionnaire that may be used in oncology clinical practice. The main findings revealed that Delphi and pretesting increased the quality of the questionnaire, making it compelling to assess breast cancer patients' comprehension and decision-making capacity about PC and ACP.

Lipid Metabolic Reprogramming Extends beyond Histologic Tumor Demarcations in Operable Human Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignancies and potentially curable only with radical surgical resection at early stages. The tumor microenvironment has been shown to be central to the development and progression of PDAC. A better understanding of how early human PDAC metabolically communicates with its environment and differs from healthy pancreas could help improve PDAC diagnosis and treatment. Here we performed deep proteomic analyses from diagnostic specimens of operable, treatment-naïve PDAC patients (n = 14), isolating four tissue compartments by laser-capture microdissection: PDAC lesions, tumor-adjacent but morphologically benign exocrine glands, and connective tissues neighboring each of these compartments. Protein and pathway levels were compared between compartments and with control pancreatic proteomes. Selected targets were studied immunohistochemically in the 14 patients and in additional tumor microarrays, and lipid deposition was assessed by nonlinear label-free imaging (n = 16). Widespread downregulation of pancreatic secretory functions was observed, which was paralleled by high cholesterol biosynthetic activity without prominent lipid storage in the neoplastic cells. Stromal compartments harbored ample blood apolipoproteins, indicating abundant microvasculature at the time of tumor removal. The features best differentiating the tumor-adjacent exocrine tissue from healthy control pancreas were defined by upregulation of proteins related to lipid transport. Importantly, histologically benign exocrine regions harbored the most significant prognostic pathways, with proteins involved in lipid transport and metabolism, such as neutral cholesteryl ester hydrolase 1, associating with shorter survival. In conclusion, this study reveals prognostic molecular changes in the exocrine tissue neighboring pancreatic cancer and identifies enhanced lipid transport and metabolism as its defining features. SIGNIFICANCE: In clinically operable pancreatic cancer, regions distant from malignant cells already display proteomic changes related to lipid transport and metabolism that affect prognosis and may be pharmacologically targeted.

Position statement of ANCP and SBGG on shared decision-making in palliative care. / Posicionamento da ANCP e SBGG sobre tomada de decisão compartilhada em cuidados paliativos.

Health care for patients with serious illnesses usually implies the need to make a large number of decisions, ranging from how information is shared to which diagnostic or therapeutic procedures will be adopted. The method of such decision-making has important implications from an individual and collective point of view and may contribute to either relieving or aggravating suffering. In this consensus document, the Bioethics Committee of the Brazilian National Academy of Palliative Care (ANCP) and the Permanent Committee on Palliative Care of the Brazilian Geriatrics and Gerontology Society (SBGG) adopt the principles of compassionate listening proposed by Saunders, of the nature of suffering proposed by Cassel, of dignity-preserving care proposed by Chochinov, and of cultural humility as a starting point for the construction of an official position of ANCP and SBGG on shared decision-making in palliative care. The position statement posits that, unlike paternalistic and consumerist models, the decision-making process in the sphere of palliative care must follow the mutualistic model of shared decision, where decisions are built based on dialogue between healthcare professionals and patients/family. The document sets forth the assumptions of this process, the limits of autonomy of patients/family and healthcare professionals and the distinction between futile and potentially inappropriate treatments, besides ratifying its incompatibility with any forms of coercion and conflict of interest foreign to the best interests of patients.

Os cuidados de saúde com pacientes portadores de doenças graves usualmente implicam a necessidade de tomada de um grande número de decisões, envolvendo desde a forma como a informação é compartilhada até quais procedimentos diagnósticos ou terapêuticos serão adotados. A maneira como tais decisões são tomadas têm importantes implicações do ponto de vista individual e coletivo, podendo contribuir tanto para o alívio como para o agravamento do sofrimento. No presente documento de consenso, o Comitê de Bioética da Academia Nacional de Cuidados Paliativos (ANCP) e a Comissão Permanente de Cuidados Paliativos da Sociedade Brasileira de Geriatria e Gerontologia (SBGG) adotam os princípios da escuta compassiva proposto por Saunders, da natureza do sofrimento proposto por Cassel, dos cuidados preservadores da dignidade propostos por Chochinov e da humildade cultural como ponto de partida para a construção de um posicionamento oficial da ANCP e SBGG acerca do processo de tomada de decisão compartilhada em cuidados paliativos. O posicionamento estabelece que, em contraposição aos modelos paternalistas e consumistas, o processo de tomada de decisão no âmbito dos cuidados paliativos deve seguir o modelo mutualista de decisão compartilhada, no qual as decisões são construídas a partir do diálogo entre profissionais de saúde e pacientes/familiares. O documento estabelece os pressupostos deste processo, os limites da autonomia de pacientes/familiares e profissionais de saúde, a distinção entre tratamentos fúteis e potencialmente inapropriados, bem como ratifica sua incompatibilidade com quaisquer formas de coerção e conflitos de interesse alheios ao melhor interesse dos pacientes.

Los cuidados de salud de pacientes portadores de enfermedades graves usualmente implican la necesidad de tomar un gran número de decisiones, que abarcan desde cómo se comparte la información hasta qué procedimientos diagnósticos o terapéuticos se adoptarán. La forma en que se toman tales decisiones tiene importantes implicaciones desde el punto de vista individual y colectivo, y puede contribuir tanto a aliviar como a agravar el sufrimiento. En el presente documento de consenso, el Comité de Bioética de la Academia Nacional de Cuidados Paliativos (ANCP) y la Comisión Permanente de Cuidados Paliativos de la Sociedad Brasileña de Geriatría y Gerontología (SBGG) adoptan los principios de la escucha compasiva propuesta por Saunders; de la naturaleza del sufrimiento propuesta por Cassel, de los cuidados preservadores de la dignidad propuestos por Chochinov y de la humildad cultural como punto de partida para la construcción de un posicionamiento oficial de la ANCP y SBGG sobre el proceso de toma de decisiones compartidas en cuidados paliativos. El posicionamiento establece que, en contraposición a los modelos paternalistas y consumistas, el proceso de toma de decisiones en el ámbito de los cuidados paliativos debe seguir el modelo mutualista de decisión compartida, donde las decisiones son construidas a partir del diálogo entre los profesionales de salud y los pacientes/familiares. El documento establece los supuestos de este proceso, los límites de la autonomía de los pacientes/familiares y de los profesionales de la salud, la distinción entre los tratamientos inútiles y los potencialmente inapropiados, así como ratifica su incompatibilidad con cualquier forma de coerción y los conflictos de intereses distintos del interés superior de los pacientes.

Assessment of Antibiotic Pharmacokinetics, Molecular Biomarkers and Clinical Status in Critically Ill Adults Diagnosed with Community-Acquired Pneumonia and Receiving Intravenous Piperacillin/Tazobactam and Hydrocortisone over the First Five Days of Intensive Care: An Observational Study (STROBE Compliant).

Severe community-acquired pneumonia (CAP) is a condition that frequently requires intensive care and, eventually, can cause to death. Piperacillin/tazobactam antibiotic therapy is employed as an empiric intravenous regimen, in many cases supplemented with intravenous bolus hydrocortisone treatment. The individual and condition-dependent pharmacokinetic properties of these drugs may lead to therapeutic failure. The impact of systemic inflammation, as well as of hydrocortisone on the altered pharmacokinetics of piperacillin is largely unknown. The protocol of a clinical study aimed at the characterization of the pharmacokinetics of piperacillin and tazobactam and its association with the concentrations of inflammatory markers and adrenal steroids during CAP therapy will be investigated in up to 40 critically ill patients. The serum concentrations of piperacillin and tazobactam, cortisol, cortisone, corticosterone and 11-deoxycortisol and interleukin-6 levels, as well as routine clinical chemistry and hematology parameters will be monitored from the beginning of treatment for up to five days. Nonparametric population pharmacokinetic modeling and Monte-Carlo simulations will be performed to make estimates of the pharmacokinetics of piperacillin and tazobactam and the probability of pharmacokinetic-pharmacodynamic target attainment. The observed individual characteristics and changes will be correlated with clinical and laboratory findings. The protocol of the observational study will be designed following the STROBE guideline.

Ecological momentary assessment of affect in depression-prone and control samples: Survey compliance and affective yield.

BACKGROUND: Ecological momentary assessment (EMA) is a high-frequency ambulatory data collection approach that has come to be widely used in emotion research. It therefore is timely to examine two features of EMA needed for a successful study: compliance with survey prompts and high affective yield (survey prompts that capture affect experience). We posit that compliance may be subject to temporal variation (time-of-day, days in study) and individual differences (depression history), and that affective yield may also differ by social context. METHODS: We examined these issues in a sample of 318 young adults (Mage = 24.7 years, SD = 2.7), including those with current depression (n = 28), remitted depression (n = 168) and never-depressed controls (n = 122) who participated in a 7-day EMA protocol of negative and positive affect (NA and PA, respectively). RESULTS: The overall compliance rate was 91% and remained stable across the survey week. However, subjects were significantly less likely to respond to the first daily prompt compared to those that followed. The likelihood of capturing NA and PA decreased with each EMA protocol day, and affective yield across social contexts differed by participants' depression status. LIMITATIONS: The sample was largely comprised of White young adults. Relative to the remitted and control groups, the sample size for the currently depressed was unbalanced. CONCLUSION: Researchers can optimize compliance and affective yield within EMA by considering depression, time-of-day, study duration, and social context. Clinicians using EMA to monitor affect may benefit from considering these parameters.

Adiposity and Smoking Mediate the Relationship Between Depression History and Inflammation Among Young Adults.

BACKGROUND: Depression is associated with inflammation, but the mechanisms underlying this association are unclear. We examined adiposity and smoking as potential pathways through which childhood depression may lead to an elevated inflammatory status among young adults. METHODS: The sample included 294 subjects with histories of depression (probands), 270 never-depressed siblings of probands (high-risk siblings), and 169 controls. C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1 (sICAM-1) were assessed in serum samples. An adiposity score was computed from body mass index and waist circumference. Smoking behavior was evaluated during an interview. Mixed-effects models were used to test whether adiposity and smoking mediate the relationship between depression and inflammation. RESULTS: Probands (p = .004), but not siblings (p = .071), had higher levels of sICAM-1 compared to controls. However, depression history and risk status had no direct effects on CRP (ps > .13) or IL-6 (ps > .16). Importantly, adiposity indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on all three inflammatory markers. Smoking indirectly mediated the effect of group (probands vs. controls; siblings vs. controls) on sICAM-1 only. CONCLUSIONS: Among young adults, the adverse inflammatory consequences of depression history are significant for sICAM-1. Adiposity and smoking are pathways through which depression can indirectly impact several inflammatory markers, suggesting possible preventive interventions to improve the immunologic and cardiovascular health of depression-prone individuals.

Posicionamento da ANCP e SBGG sobre tomada de decisão compartilhada em cuidados paliativos / Posicionamiento de la ANCP y SBGG sobre la toma de decisiones compartida en cuidados paliativos / Position statement of ANCP and SBGG on shared decision-making in palliative care

Os cuidados de saúde com pacientes portadores de doenças graves usualmente implicam a necessidade de tomada de um grande número de decisões, envolvendo desde a forma como a informação é compartilhada até quais procedimentos diagnósticos ou terapêuticos serão adotados. A maneira como tais decisões são tomadas têm importantes implicações do ponto de vista individual e coletivo, podendo contribuir tanto para o alívio como para o agravamento do sofrimento. No presente documento de consenso, o Comitê de Bioética da Academia Nacional de Cuidados Paliativos (ANCP) e a Comissão Permanente de Cuidados Paliativos da Sociedade Brasileira de Geriatria e Gerontologia (SBGG) adotam os princípios da escuta compassiva proposto por Saunders, da natureza do sofrimento proposto por Cassel, dos cuidados preservadores da dignidade propostos por Chochinov e da humildade cultural como ponto de partida para a construção de um posicionamento oficial da ANCP e SBGG acerca do processo de tomada de decisão compartilhada em cuidados paliativos. O posicionamento estabelece que, em contraposição aos modelos paternalistas e consumistas, o processo de tomada de decisão no âmbito dos cuidados paliativos deve seguir o modelo mutualista de decisão compartilhada, no qual as decisões são construídas a partir do diálogo entre profissionais de saúde e pacientes/familiares. O documento estabelece os pressupostos deste processo, os limites da autonomia de pacientes/familiares e profissionais de saúde, a distinção entre tratamentos fúteis e potencialmente inapropriados, bem como ratifica sua incompatibilidade com quaisquer formas de coerção e conflitos de interesse alheios ao melhor interesse dos pacientes.

Los cuidados de salud de pacientes portadores de enfermedades graves usualmente implican la necesidad de tomar un gran número de decisiones, que abarcan desde cómo se comparte la información hasta qué procedimientos diagnósticos o terapéuticos se adoptarán. La forma en que se toman tales decisiones tiene importantes implicaciones desde el punto de vista individual y colectivo, y puede contribuir tanto a aliviar como a agravar el sufrimiento. En el presente documento de consenso, el Comité de Bioética de la Academia Nacional de Cuidados Paliativos (ANCP) y la Comisión Permanente de Cuidados Paliativos de la Sociedad Brasileña de Geriatría y Gerontología (SBGG) adoptan los principios de la escucha compasiva propuesta por Saunders; de la naturaleza del sufrimiento propuesta por Cassel, de los cuidados preservadores de la dignidad propuestos por Chochinov y de la humildad cultural como punto de partida para la construcción de un posicionamiento oficial de la ANCP y SBGG sobre el proceso de toma de decisiones compartidas en cuidados paliativos. El posicionamiento establece que, en contraposición a los modelos paternalistas y consumistas, el proceso de toma de decisiones en el ámbito de los cuidados paliativos debe seguir el modelo mutualista de decisión compartida, donde las decisiones son construidas a partir del diálogo entre los profesionales de salud y los pacientes/familiares. El documento establece los supuestos de este proceso, los límites de la autonomía de los pacientes/familiares y de los profesionales de la salud, la distinción entre los tratamientos inútiles y los potencialmente inapropiados, así como ratifica su incompatibilidad con cualquier forma de coerción y los conflictos de intereses distintos del interés superior de los pacientes.

Health care for patients with serious illnesses usually implies the need to make a large number of decisions, ranging from how information is shared to which diagnostic or therapeutic procedures will be adopted. The method of such decision-making has important implications from an individual and collective point of view and may contribute to either relieving or aggravating suffering. In this consensus document, the Bioethics Committee of the Brazilian National Academy of Palliative Care (ANCP) and the Permanent Committee on Palliative Care of the Brazilian Geriatrics and Gerontology Society (SBGG) adopt the principles of compassionate listening proposed by Saunders, of the nature of suffering proposed by Cassel, of dignity-preserving care proposed by Chochinov, and of cultural humility as a starting point for the construction of an official position of ANCP and SBGG on shared decision-making in palliative care. The position statement posits that, unlike paternalistic and consumerist models, the decision-making process in the sphere of palliative care must follow the mutualistic model of shared decision, where decisions are built based on dialogue between healthcare professionals and patients/family. The document sets forth the assumptions of this process, the limits of autonomy of patients/family and healthcare professionals and the distinction between futile and potentially inappropriate treatments, besides ratifying its incompatibility with any forms of coercion and conflict of interest foreign to the best interests of patients.

Age related sex differences in maladaptive regulatory responses to sadness: A study of youths at high and low familial risk for depression.

Offspring of parents with depression histories are at increased risk of developing depression and also report maladaptive ways of self-regulating sadness. Maladaptive regulation of sadness tends to be more prevalent among females than males and has been proposed as one explanation of sex differences in depression rates that emerge around mid-adolescence. However, there is scant information about the age at which the sex differences in maladaptive regulatory responses become evident and whether such age-related sex differences vary depending on depression risk. The present study examined two samples aged 8-18 years: 86 offspring of emotionally healthy parents and 98 offspring of parents with depression histories. Subjects were clinically assessed and provided self-reports of maladaptive responses to sadness. In the combined samples, sex differences in maladaptive responses were significant at age 12.5 years and older ages (i.e., chronologically earlier than the documented emergence of sex differences in depression). While in the high-risk group, sex differences in maladaptive regulatory responses were significant at 12.11 years of age and older, in the low-risk group there was no age at which sex differences were significant. Our findings support the possible mechanistic role of maladaptive emotion regulation in the emergence of sex disparities in depression rates and have implications for prevention.

Childhood-onset depression and arterial stiffness in young adulthood.

OBJECTIVES: The literature on childhood-onset depression and future compromised vascular function is suggestive but limited. The objective of this study was to determine if arterial stiffness, a predictor of future cardiovascular disease (CVD), measured in young adulthood, is associated with childhood-onset depression. METHODS: Cardiometabolic risk factors and pulse wave velocity (PWV), a measure of arterial stiffness, were cross-sectionally assessed in young adults with a history of childhood-onset depression (clinical diagnosis of major depressive episode or dysthymic disorder; N = 294 probands; initially recruited via child mental health facilities across Hungary; mean age of first depressive episode = 10.4 years), their never-depressed full biological siblings (N = 269), and never-depressed controls (N = 169). The mean ages of probands, siblings, and controls at the PWV visit were 25.6, 25.0, and 21.7 years, respectively, and 8.8% of the probands were in a current depressive episode. RESULTS: Controlling for age, sex, age*sex, education, and family clusters, PWV (m/s) did not statistically differ across the groups (probands = 7.01; siblings = 6.98; controls = 6.81). However, after adjusting for key covariates, there were several across-group differences in CVD risk factors: compared to controls, probands and siblings had higher diastolic blood pressure and lower high-density lipoprotein cholesterol, probands had higher triglycerides, and siblings had higher body mass index (all p < 0.05). CONCLUSION: We found limited evidence of an association between a history of childhood-onset depression and young adulthood arterial stiffness. However, our findings of elevated cardiovascular risk factors in those with childhood-onset depression suggest that pediatric depression may predispose to increased CVD risk later in life and warrants further investigation.

Cell lines and clearing approaches: a single-cell level 3D light-sheet fluorescence microscopy dataset of multicellular spheroids.

Nowadays, three dimensional (3D) cell cultures are widely used in the biological laboratories and several optical clearing approaches have been proposed to visualize individual cells in the deepest layers of cancer multicellular spheroids. However, defining the most appropriate clearing approach for the different cell lines is an open issue due to the lack of a gold standard quantitative metric. In this article, we describe and share a single-cell resolution 3D image dataset of human carcinoma spheroids imaged using a light-sheet fluorescence microscope. The dataset contains 90 multicellular cancer spheroids derived from 3 cell lines (i.e. T-47D, 5-8F, and Huh-7D12) and cleared with 5 different protocols, precisely ClearT, ClearT2, CUBIC, ScaleA2, and Sucrose. To evaluate image quality and light penetration depth of the cleared 3D samples, all the spheroids have been imaged under the same experimental conditions, labelling the nuclei with the DRAQ5 stain and using a Leica SP8 Digital LightSheet microscope. The clearing quality of this dataset was annotated by 10 independent experts and thus allows microscopy users to qualitatively compare the effects of different optical clearing protocols on different cell lines. It is also an optimal testbed to quantitatively assess different computational metrics evaluating the image quality in the deepest layers of the spheroids.

A quantitative metric for the comparative evaluation of optical clearing protocols for 3D multicellular spheroids.

3D multicellular spheroids quickly emerged as in vitro models because they represent the in vivo tumor environment better than standard 2D cell cultures. However, with current microscopy technologies, it is difficult to visualize individual cells in the deeper layers of 3D samples mainly because of limited light penetration and scattering. To overcome this problem several optical clearing methods have been proposed but defining the most appropriate clearing approach is an open issue due to the lack of a gold standard metric. Here, we propose a guideline for 3D light microscopy imaging to achieve single-cell resolution. The guideline includes a validation experiment focusing on five optical clearing protocols. We review and compare seven quality metrics which quantitatively characterize the imaging quality of spheroids. As a test environment, we have created and shared a large 3D dataset including approximately hundred fluorescently stained and optically cleared spheroids. Based on the results we introduce the use of a novel quality metric as a promising method to serve as a gold standard, applicable to compare optical clearing protocols, and decide on the most suitable one for a particular experiment.

Sympathetic arousal during the processing of dysphoric affect by youths at high and low familial risk for depression.

Youths at high risk for depression have been shown to have problems in repairing their own sad mood. Given that sympathetic arousal has been implicated both in the experience and regulation of affect, an atypical pattern of arousal may be one of the factors that contribute to mood repair problems. In the current study, we measured sympathetic arousal of never-depressed youths at high (n = 56) and low (n = 67) familial risk for depression during sad mood induction and instructed mood repair. Sympathetic arousal was indexed by skin conductance level (SCL) and cardiac pre-ejection period (PEP); mood repair outcome was indexed by self-rated affect. High-risk youths demonstrated increased SCL during sadness induction, which persisted during mood repair; low-risk youths evidenced increased SCL only during mood repair. Shortened PEP was evident only among high-risk youths and only during mood repair. Furthermore, shortened PEP during mood induction predicted less successful mood repair in the low-risk but not in the high-risk group. The findings suggest that: (a) depression-prone youths differ from control peers in patterns of sympathetic responses to emotional stimuli, which may impair their ability to relieve sadness, and (b) activation patterns differ across subsystems (SCL vs. PEP) of sympathetic activity, in conjunction with depression risk status.

3D-Cell-Annotator: an open-source active surface tool for single-cell segmentation in 3D microscopy images.

SUMMARY: Segmentation of single cells in microscopy images is one of the major challenges in computational biology. It is the first step of most bioimage analysis tasks, and essential to create training sets for more advanced deep learning approaches. Here, we propose 3D-Cell-Annotator to solve this task using 3D active surfaces together with shape descriptors as prior information in a semi-automated fashion. The software uses the convenient 3D interface of the widely used Medical Imaging Interaction Toolkit (MITK). Results on 3D biological structures (e.g. spheroids, organoids and embryos) show that the precision of the segmentation reaches the level of a human expert. AVAILABILITY AND IMPLEMENTATION: 3D-Cell-Annotator is implemented in CUDA/C++ as a patch for the segmentation module of MITK. The 3D-Cell-Annotator enabled MITK distribution can be downloaded at: www.3D-cell-annotator.org. It works under Windows 64-bit systems and recent Linux distributions even on a consumer level laptop with a CUDA-enabled video card using recent NVIDIA drivers. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Cardiac vagal control mediates the relation between past depression and blood pressure several years later among young adults.

Depression has been associated with high blood pressure (BP). However, the mechanisms of the relation between depression and high BP are unclear. We therefore examined whether impaired cardiac vagal control, indexed as low levels of resting respiratory sinus arrhythmia (RSA), serves as a route from depression to high BP. The sample included 125 subjects with histories of depression (probands), 123 never depressed siblings of probands (high-risk siblings), and 156 controls. Resting RSA was assessed at Time 1 (T1) along with BP when subjects were adolescents (Mage  = 16.3 years); systolic and diastolic BP (SBP and DBP) were measured again at Time 2 (T2) when subjects were young adults (Mage  = 22.3 years). Linear mixed-effects models were used to examine the group differences in resting RSA and T2 BP outcomes and to test for RSA mediation of the relation between depression (history or being at high risk) and BP. Resting RSA was lower among probands than controls but was similar among high-risk siblings and controls, while the subject groups did not differ in T2 SBP or DBP. Controlling for T1 BP, depression history indirectly affected T2 DBP (but not SBP) through resting RSA. The findings suggest that, although the direct detrimental effects of depression on BP are not yet evident in young adulthood, among those with depression histories, impaired cardiac vagal control appears to serve as a mechanism of elevated DBP.