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The world is experiencing a moment of political polarization between liberal and conservative ideas, which has aggravated since the arrival of the Covid-19. Many countries (Brazil included) have been experiencing the generalized occurrence of people fighting over politics, in contexts including family, workplace, friendships, and romantic relationships. Over the past 2 years, it has been possible to observe an unexpected and overwhelming effect of the political climate on psychotherapy patients, some of whom have started to actively look for therapists who share their convictions. Brazil is experiencing a moment of severe sanitary, economic, social, and political crisis, which is directly affecting our patients. Nevertheless, the impact of the political climate on our population has not been systematically investigated. However, as the political environment is an inherent part of the social component of the psychosocial model, it is important that mental health professionals be prepared to have this conversation with their patients. This highlights the need to address these difficulties in supervision, rounds, and clinical discussions. [ABSTRACT FROM AUTHOR]

Objective To evaluate the development and implementation of clinical practice guidelines for the management of depression globally. Methods We conducted a systematic review of existing guidelines for the management of depression in adults with major depressive or bipolar disorder. For each identified guideline, we assessed compliance with measures of guideline development quality (such as transparency in guideline development processes and funding, multidisciplinary author group composition, systematic review of comparative efficacy research) and implementation (such as quality indicators). We compared guidelines from low- and middle-income countries with those from high-income countries. Findings We identified 82 national and 13 international clinical practice guidelines from 83 countries in 27 languages. Guideline development processes and funding sources were explicitly specified in a smaller proportion of guidelines from low- and middle-income countries (8/29; 28%) relative to high-income countries (35/58; 60%). Fewer guidelines (2/29; 7%) from low- and middle-income countries, relative to high-income countries (22/58; 38%), were authored by a multidisciplinary development group. A systematic review of comparative effectiveness was conducted in 31% (9/29) of low- and middle-income country guidelines versus 71% (41/58) of high-income country guidelines. Only 10% (3/29) of low- and middle-income country and 19% (11/58) of high-income country guidelines described plans to assess quality indicators or recommendation adherence. Conclusion Globally, guideline implementation is inadequately planned, reported and measured. Narrowing disparities in the development and implementation of guidelines in low- and middle-income countries is a priority. Future guidelines should present strategies to implement recommendations and measure feasibility, cost--effectiveness and impact on health outcomes. [ABSTRACT FROM AUTHOR]

Physical activity (PA) has been proposed as a determinant of cognitive function and is one component of energy balance (EB). EB is the difference between energy intake (EI) and the total daily energy expenditure (TDEE). TDEE is a combination of resting metabolic rate (RMR), thermic effect of food and PA. The potential role of each of these components on cognitive function has not yet been systemically investigated. We aim to evaluate the association between each component of EB on cognition, using baseline and longitudinal data from a clinical trial of caloric restriction (CR). This is a parallel-group, randomized clinical trial comparing two years of 25% CR with two years of ad libitum diet (AL), with 220 healthy volunteers of both sex, aged between 21 and 50 years and initial BMI ≥ 22 kg/m2 and <28 kg/m2. Body weight, fat mass (FM), fat-free mass (FFM), and bone mineral content were evaluated, as well as RMR, TDEE, cognitive performance and baseline energy intake. A 30 min/day of a moderate level on a minimum of 5 days/week was advised as PA measure. Longitudinal analysis demonstrated that the influence of CR in the improvement of cognitive performance was moderated by changes in RMR, suggesting that in individuals submitted to CR, the cognitive performance and the RMR improved proportionally, independently of changes in EI and body mass. EB and homeostasis are crucial to modulate the RMR. Moreover, RMR presents an important influence on cognitive function in individuals submitted to CR in a long term. [ABSTRACT FROM AUTHOR]

• Digital phenotyping is the continuous acquisition of data on human‐machine interactions and behaviors via smartphones/personal devices. • Using digital phenotypes for the assessment of mood disorders may help identify clinically meaningful inter/intra-individual variabilities. • Integration of digital phenotypes with other traditional biomarkers may increase the predictive power of critical outcomes in mood disorders. Major Depressive Disorder (MDD) and bipolar disorder (BD) are still under recognized and undertreated, especially in primary care settings. One of the challenges faced by clinicians is the remarkable inter-individual variability among patients with these conditions. In addition, each patient with MDD and BD experiences a unique pattern of longitudinal changes across time, i.e., intra-individual variability can also be problematic. The immense amount of data generated and collected through the use of smartphones or personal devices offers an opportunity to obtain continuous and reliable information on each individual's behavior, a less burdensome way to capture both intra and inter-individual variability over time. Digital phenotypes (DP) are a promising strategy to be integrated with other "Omics" platforms for prediction of relevant outcomes in mood disorders, including but not restricted to, relapse, recurrence, cognitive decline and functional impairment. Despite existing limitations and some skepticism, digital phenotyping represents a field in great expansion and might eventually constitute a feasible strategy in biomarkers research for mood disorders. [ABSTRACT FROM AUTHOR]

Highlights • Mood disorders could have metabolic manifestations as part of the psychiatric syndrome. • Diet interventions present a unique and potentially useful treatment avenue for mood disorders. • Preliminary data suggest a potential role for ketogenic diet in the treatment of mood disorders. Abstract Despite significant advances in pharmacological and non-pharmacological treatments, mood disorders remain a significant source of mental capital loss, with high rates of treatment resistance, requiring a coordinated effort in investigation and development of efficient, tolerable and accessible novel interventions. Ketogenic diet (KD) is a low-carb diet that substantially changes the energetic matrix of the body including the brain. It has been established as an effective anticonvulsant treatment, and more recently, the role of KD for mental disorders has been explored. Ketogenic diet has profound effects in multiple targets implicated in the pathophysiology of mood disorders, including but not limited to, glutamate/GABA transmission, monoamine levels, mitochondrial function and biogenesis, neurotrophism, oxidative stress, insulin dysfunction and inflammation. Preclinical studies, case reports and case series have demonstrated antidepressant and mood stabilizing effects of KD, however, to date, no clinical trials for depression or bipolar disorder have been conducted. Because of its potential pleiotropic benefits, KD should be considered as a promising intervention in research in mood disorder therapeutics, especially in treatment resistant presentations. [ABSTRACT FROM AUTHOR]

Highlights • Numerous studies indicate that probiotics have anti-inflammatory effects. • Immune-inflammatory modulation may mediate the antidepressant effects of probiotics. • Probiotics may be more effective in depressed subgroups with elevated inflammation. • Future studies should parse out the heterogeneous effects of different probiotics. Abstract During the past decade, there has been renewed interest in the relationship between brain-based disorders, the gut microbiota, and the possible beneficial effects of probiotics. Emerging evidence suggests that modifying the composition of the gut microbiota via probiotic supplementation may be a viable adjuvant treatment option for individuals with major depressive disorder (MDD). Convergent evidence indicates that persistent low-grade inflammatory activation is associated with the diagnosis of MDD as well as the severity of depressive symptoms and probability of treatment response. The objectives of this review are to (1) evaluate the evidence supporting an anti-inflammatory effect of probiotics and (2) describe immune system modulation as a potential mechanism for the therapeutic effects of probiotics in populations with MDD. A narrative review of studies investigating the effects of probiotics on systemic inflammation was conducted. Studies were identified using PubMed/Medline, Google Scholar, and clinicaltrials.gov (from inception to November 2017) using the following search terms (and/or variants): probiotic , inflammation , gut microbiota , and depression. The available evidence suggests that probiotics should be considered a promising adjuvant treatment to reduce the inflammatory activation commonly found in MDD. Several controversial points remain to be addressed including the role of leaky gut, the role of stress exposure, and the role of blood-brain-barrier permeability. Taken together, the results of this review suggest that probiotics may be a potentially beneficial, but insufficiently studied, antidepressant treatment intervention. [ABSTRACT FROM AUTHOR]

The objective of this study was to compare the expression of genes involved in the reelin pathway, in the post-mortem brain of individuals with schizophrenia (SZ) and mood disorders (MD) with a healthy control (HC) group; and to investigate the role f body mass index (BMI) as a potential mediator. The “Gene Expression in Postmortem dlPFC and Hippocampus from Schizophrenia and Mood Disorders” study holds microarray data on individuals with SZ, MD and HCs (from whom 849 specimens are from the dlPFC and 579 from the hippocampus). mRNA data was obtained using HumanHT-12 v4 BeadChip arrays (Illumina). Multivariate analysis of covariance were used to investigate the main effects of group and relevant covariates on RELNm, NOTCH1, GRIN1m, GRIN3A, CAMK2Gm, CAMK2A, CAMK2Bm, CAMK2N2, GRIN2Bm, GRIN2A, CREBBPm, APOE, LDLR and DAB1 gene expression. In the dlPFC, individuals with SZ had higher expression, relative to HCs, of APOE. Individuals with MD had higher expression, relative to HCs, of CAMK2A, CAMK2N2, and GRIN2Bm. Moreover, individuals with MD had higher expression, relative to SZ patients, of CAMK2N2. There were significant group by BMI effects for expression of RELN, CAMK2A, CAMK2N2, and GRIN2A. In the hippocampus, individuals with MD had lower expression, relative to HCs, of APOE. The results of this study suggest that the expression of genes related to the reelin pathway could be different between individuals with SZ and MD and healthy controls, with a greater vulnerability associated with greater BMI. [ABSTRACT FROM AUTHOR]

Heterogeneity in response to conventional antidepressants is a well-recognized limitation of evidence-based pharmacological treatments of major depressive disorder (MDD). Abnormal activation of inflammatory pathways is postulated as one likely mechanism contributing to treatment resistance in MDD. In a subset of depressed patients, the balance between pro- and anti-inflammatory cytokines is thought to be altered, causing mood symptoms due to inflammation, as seen in co-morbid depression associated with inflammatory conditions (e.g. psoriasis, hepatitis C, inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis). The objectives of the current narrative review are to critically evaluate the literature about the effects of cytokine blockers on clinical outcomes in MDD and in the reduction of depressive symptom severity in individuals using these medications primarily to treat inflammatory conditions. A small number of clinical trials assessing the effects of cytokine blockers for depression and depressive symptoms have been completed. These trials suggest that in individuals with immune dysfunction (e.g. elevated pro-inflammatory cytokine levels), cytokine blockers may allow for improved clinical outcomes in MDD that would not be achievable with current conventional antidepressants alone. Additional well-designed clinical trials to assess the clinical utility of anti-inflammatory medications for the treatment of depression and depressive symptoms are merited. Further, the use of anti-inflammatories show promise for disease modifying effects that may alter illness trajectory, rather than solely ameliorating current mood symptoms. [ABSTRACT FROM AUTHOR]

The putative role of gluten in the pathophysiology of severe mental illnesses remains uncertain and there is doubt about the possible benefit of gluten-free diets for individuals affected by psychosis and mood disorders. The objective of this review was to summarize the findings linking gluten related conditions to pathophysiological substrates implicated in schizophrenia and mood disorders and review the evidences of potential benefits of glute-free diets in these populations. A literature search was conducted within PubMed and Scielo databases including references from inception until March 1st 2017. The strategy search was to use the key words “gluten”, “celiac disease”, “wheat”, “bipolar disorder”, “mood disorders”, “psychosis”, “schizophrenia”, “depression”. In the review about the potential efficacy of gluten-free diets in severe mental illnesses, we included only studies with original data, including cross sectional and longitudinal studies and clinical trials. Book chapters, review articles and meta-analysis and republished data were excluded. Although the current available evidences suggest that people with celiac disease or gluten allergy could have a slightly higher risk of schizophrenia and mood disorders compared to the general population, the literature review reveals significant inaccuracies in the data. There is insufficient evidence to recommend gluten-free diets for populations with psychosis and mood disorders. [ABSTRACT FROM AUTHOR]

Despite overwhelming evidence that lithium prevents episodes of bipolar disorder and suicide attempts and suicide, (Tondo et al. [8]) there has been a consistent decline in its use in the past decades, especially in North America. They concluded that lithium use in Spain is in line with the international guidelines and that the first reason not to prescribe lithium was related to adverse effects and not its practical use or effectiveness. [Extracted from the article]

Background: Bipolar disorder (BD) is associated with chronic low-grade inflammation, several medical comorbidities and a decreased life expectancy. Metabolic-inflammatory changes have been postulated as one of the main links between BD and medical comorbidity, although there are few studies exploring possible mechanisms underlying this relationship. Therefore, the aims of the current narrative review were 1) synthesize the evidence for metabolic-inflammatory changes that may facilitate the link between medical comorbidity and BD and 2) discuss therapeutic and preventive implications of these pathways.Methods: The PubMed and Google Scholar databases were searched for relevant studies.Results: Identified studies suggested that there is an increased risk of medical comorbidities, such as autoimmune disorders, obesity, diabetes and cardiovascular disease in patients with BD. The association between BD and general medical comorbidities seems to be bidirectional and potentially mediated by immune dysfunction. Targeting the metabolic-inflammatory-mood pathway may potential yield improved outcomes in BD; however, further study is needed to determine which specific interventions may be beneficial.Limitations: The majority of identified studies had cross-sectional designs, small sample sizes and limited measurements of inflammation.Conclusions: Treatment and prevention of general medical comorbidities in mood disorders should include preferential prescribing of metabolically neutral agents and adjunctive lifestyle modifications including increased physical activity, improved diet and decreased substance abuse. In addition, the use of anti-inflammatory agents could be a relevant therapeutic target in future research. [ABSTRACT FROM AUTHOR]

Lipidomics or lipid-profiling is a lipid-targeted metabolomics approach aiming at comprehensive analysis of lipids in biological systems. The extent of information in the genomic and proteomic fields is greater than that in the lipidomics field, because of the complex nature of lipids and the limitations of tools for analysis. Modern technological advances in mass spectrometry and chromatography have greatly improved the developments and applications of metabolic profiling of diverse lipids in complex biological samples. Lipidomics will not only provide insights into the specific functions of lipid species in health and disease, but will also identify potential biomarkers for establishing preventive or therapeutic programs for human diseases. In this review, emphasis is given to the current advances in lipidomics technologies and their applications in disease biomarker discovery, and its clinical application. The application of lipidomics in clinical studies may provide new insights into lipid profiling and pathophysiological mechanisms. We also discuss the lipidomics for the future perspectives and their potential problems. [ABSTRACT FROM AUTHOR]

Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) has been associated with cognitive impairment during depressed, manic and euthymic periods. Inflammation has been shown to be involved in the pathophysiology of BD and cognitive impairment.Methods: For this systematic review, the MEDLINE/PubMed, Embase, Google Scholar and ClinicalTrials.gov databases were searched for relevant articles assessing the association between cognitive function and inflammatory markers in BD subjects. A discussion of potential mechanisms and therapeutic implications is also included to provide further context to the subject matter.Results: Eight studies, including a total of 555 BD subjects, assessing the association between cognitive function and inflammatory markers were identified. Cognitive dysfunction was associated with elevated levels of pro-inflammatory markers YKL40, IL-6, sCD40L, IL-1Ra, hsCRP and TNF-α. Mechanistically, elevation in inflammatory cytokines alters monoamine levels leading to cognitive and affective dysfunction. Neuro-inflammation, manifesting as microglial activation, leads to increased oxidative stress, pathologic synaptic pruning and impaired neuroplasticity in key brain regions sub-serving mood and cognition. Immune dysfunction also activates the hypothalamic-pituitary-adrenal (HPA) axis leading to hypercortisolemia and metabolic dysfunction, further promoting neuronal dysfunction. Anti-inflammatory agents are therefore currently being investigated in the treatment of BD and appear to exert an antidepressant effect; however, cognitive outcomes have yet to be reported.Conclusion: Several studies suggest that immune dysfunction is associated with cognitive impairment in BD. Several neurobiological pathways have been identified whereby immune dysfunction may promote cognitive impairment in BD. Future investigations of anti-inflammatory agents targeting cognitive function as a treatment outcome are merited. [ABSTRACT FROM AUTHOR]

Obesity and mood disorders are highly prevalent and co-morbid. Epidemiological studies have highlighted the public health relevance of this association, insofar as both conditions and its co-occurrence are associated with a staggering illness-associated burden. Accumulating evidence indicates that obesity and mood disorders are intrinsically linked and share a series of clinical, neurobiological, genetic and environmental factors. The relationship of these conditions has been described as convergent and bidirectional; and some authors have attempted to describe a specific subtype of mood disorders characterized by a higher incidence of obesity and metabolic problems. However, the nature of this association remains poorly understood. There are significant inconsistencies in the studies evaluating metabolic and mood disorders; and, as a result, several questions persist about the validity and the generalizability of the findings. An important limitation in this area of research is the noteworthy phenotypic and pathophysiological heterogeneity of metabolic and mood disorders. Although clinically useful, categorical classifications in both conditions have limited heuristic value and its use hinders a more comprehensive understanding of the association between metabolic and mood disorders. A recent trend in psychiatry is to move toward a domain specific approach, wherein psychopathology constructs are agnostic to DSM-defined diagnostic categories and, instead, there is an effort to categorize domains based on pathogenic substrates, as proposed by the National Institute of Mental Health (NIMH) Research Domain Criteria Project (RDoC). Moreover, the substrates subserving psychopathology seems to be unspecific and extend into other medical illnesses that share in common brain consequences, which includes metabolic disorders. Overall, accumulating evidence indicates that there is a consistent association of multiple abnormalities in neuropsychological constructs, as well as correspondent brain abnormalities, with broad-based metabolic dysfunction, suggesting, therefore, that the existence of a “metabolic-mood syndrome” is possible. Nonetheless, empirical evidence is necessary to support and develop this concept. Future research should focus on dimensional constructs and employ integrative, multidisciplinary and multimodal approaches. [ABSTRACT FROM AUTHOR]

Objective: Advances in our knowledge of mental disorder (MD) genetics have contributed to a better understanding of their pathophysiology. Nonetheless, several questions and doubts persist. Recent studies have focused on environmental influences in the development of MDs, and the advent of neuroscientific methodologies has provided new perspectives. Early life events, such as childhood stress, may affect neurodevelopment through mechanisms such as gene-environment interactions and epigenetic regulation, thus leading to diseases in adulthood. The aim of this paper is to review the evidence regarding the role of the environment, particularly childhood stress, in the pathophysiology of MD. Methodology- We reviewed articles that evaluated environmental influences, with a particular focus on childhood trauma, brain morphology, cognitive functions, and the development of psychopathology and MD. Results and Conclusion: MRI studies have shown that exposure to trauma at an early age can result in several neurostructural changes, such as the reduction of the hippocampus and corpus callosum. Cognitive performance and functioning are also altered in this population. Finally, childhood stress is related to an increased risk of developing MD such as depression, bipolar disorder, schizophrenia and substance abuse. We conclude that there is robust evidence of the role of the environment, specifically adverse childhood experiences, in various aspects of MD. [ABSTRACT FROM AUTHOR]

Background: Theory of mind (ToM) is a field of social cognition that deals with the individual's cognitive ability to interpret or infer the mental states of others based on previous knowledge. Recently, research has shown that this ability is compromised in patients with some psychopathologies, e.g., schizophrenia and autistic disorder. Investigators have also shown that deficits in ToM have impacts on social functioning and, consequently, on quality of life. Even though ToM studies have recently grown in number, some problems still remain (e.g., the difficulty of standardized tools to assess ToM in different languages). Objectives: To describe the translation and adaptation into Brazilian Portuguese of two of the most important and widely used ToM tasks, namely, the Theory of Mind Stories and the Hinting Task. Method: The process included the following steps: 1) translation; 2) production of a single translated version and review by specialists; 3) back-translation into English; 4) review by an English-speaking specialist; 5) adaptation of marked corrections; and 6) pilot application in a group representative of the target population (people with schizophrenia). Results: A final translated version was obtained for each of the tasks. Both instruments were well understood by participants and can now be used in the Brazilian experimental setting. Conclusion: The availability of two major ToM tasks in Brazilian Portuguese facilitates the conduction of research on the topic in Brazil. In the future, this could help design clinical interventions aimed at people with social and cognitive difficulties. [ABSTRACT FROM AUTHOR]

Abstract: Background: The staggering illness burden associated with Bipolar Disorder (BD) invites the need for primary prevention strategies. Before preventative strategies can be considered in individuals during a pre-symptomatic period (i.e., at risk), unraveling the mechanistic steps wherein external stress is transduced and interacts with genetic vulnerability in the early stages of BD will be a critical conceptual necessity. Methods: Herein we comprehensively review extant studies reporting on stress and bipolar disorder. The overarching aim is to propose a conceptual framework to inform research about the role of stress in the pathophysiology of BD. Computerized databases i.e. PubMed, PsychInfo, Cochrane Library and Scielo were searched using the following terms: “bipolar disorder” cross-referenced with “stress”, “general reaction to stress”, “resilience”, “resistance”, “recovery” “stress–diathesis”, “allostasis”, and “hormesis”. Results: Data from literature indicate the existence of some theoretical models to understand the influence of stress in the pathophysiology of BD, including classical stress–diathesis model and new models such as allostasis and hormesis. In addition, molecular mechanisms involved in stress adaptation (resistance, resilience and recovery) can also be translated in research strategies to investigate the impact of stress in the pathophysiology of BD. Limitations: Most studies are retrospective and/or cross sectional, do not consider the period of development, assess brain function with only one or few methodologies, and use animal models which are not always similar to human phenotypes. Conclusion: The interaction between stress and brain development is dynamic and complex. In this article we proposed a theoretical model for investigation about the role of stress in the pathophysiology of BD, based on the different kinds of stress adaptation response and their putative neurobiological underpinnings. [Copyright &y& Elsevier]

Abstract: Background: The high prevalence, recurrence rate, chronicity, and illness burden in bipolar disorder (BD) are well documented. Moreover, insufficient response with conventional pharmacological and manual-based psychosocial interventions, as well as evidence of illness progression and acceleration, invite the need for early detection and primary prevention. Methods: Herein we comprehensively review extant studies reporting on a bipolar prodrome. The overarching aim is to propose a predictive algorithm (i.e. prediction of BD in at-risk populations) integrating genetic (i.e. family history), environmental (e.g. childhood maltreatment) and biological markers (i.e. BDNF, inflammatory and oxidative stress markers). Computerized databases i.e. Pubmed, PsychInfo, Cochrane Library and Scielo were searched using the followed terms: bipolar disorder cross-referenced with prodromal, preclinical, at risk mental states, clinical high risk, ultra high risk, biomarkers, brain-derived neurotrophic factor, inflammation, cytokines, oxidative stress, prediction and predictive model. Results: Available evidence indicates that a prodrome to bipolar disorder exists. Commonly encountered features preceding the onset of a manic episode are affective lability, irritability, anger, depression, anxiety, substance use disorders, sleep disorders, as well as disturbances in attention and cognition. Non-specificity and insufficient sensitivity have hampered the development of an adequate prediction algorithm. Limitations: Limitations include biases associated with retrospective studies, poor characterization of clinical high risk, inadequacy of prospective studies regarding sample selection and absence of specificity of risk states. Conclusion: We propose a hypothetical prediction algorithm that is combinatorial in approach that attempts to integrate family history, early adversity, and selected biomarkers. [Copyright &y& Elsevier]

Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses. [ABSTRACT FROM AUTHOR]

Objective: This article aims to review Latin America’s early intervention services in psychosis and to shed light into their challenges and particularities. Method: An internet-based search comprising medical societies’ websites, published articles, and major universities’ websites was conducted and the results were critically discussed. Results: Latin American countries are profoundly deficient in specialized early intervention services. Our search found seven target services, four of which are based in urban areas of Brazil, inside tertiary hospitals or universities. Among the initiatives advanced by these centers, there are partnerships with the public educational system and other community-based efforts toward knowledge transfer. On the other hand, several challenges remain to be overcome, especially in relation to their expansion, which is necessary to match the existing demand. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To report on the presence of current and lifetime eating disorders (ED) in a well-defined sample of 137 female individuals with bipolar disorder type I. Methods: Trained psychiatrists interviewed the patients, and the diagnoses of BD and comorbidities were confirmed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Axis I Disorders. Clinical and demographic characteristics of both groups (group with ED vs. group without ED) were compared. Results: Female patients with ED had an earlier onset of BD and an increased number of mood episodes, predominantly depressive. Women in the ED group also had higher rates of comorbidity with substance use disorders and anxiety disorders and reported a history of suicide attempts more frequently than women without ED. Conclusion: The presence of ED is a correlate of severity of BD type I, and interventions should be developed to minimize distress and suicide risk and to improve treatment outcome. [Copyright &y& Elsevier]

de Macedo-Soares MB, Brietzke E, da Silva Dias R, Mendonca T, Moreira C, Lafer B. A comparison of the symptomatic profile between two consecutive depressive episodes in patients with bipolar disorder type I. To compare the variability of patterns of depressive symptoms between two consecutive depressive episodes in patients with bipolar disorder type I. Review of prospectively collected data from 136 subjects of an out-patient bipolar unit from 1997 to 2007. Binomial statistics was used for the analysis of Hamilton Depression Rating Scale (HDRS)-31 items of the first and second episodes, and the correlation of the HDRS-31 item scores of both episodes was determined using the Spearman coefficient. Ten depressive symptoms showed a significant correlation between index and subsequent episodes: psychological anxiety, somatic anxiety, somatic symptoms, diurnal variation, paranoid symptoms, obsessive and compulsive symptoms, hypersomnia, loss of appetite and helplessness. Only four symptoms were stable in both statistical tests: paranoid symptoms, obsessive-compulsive symptoms, loss of appetite and hypersomnia. Paranoid and obsessive-compulsive symptoms, loss of appetite and hypersomnia tended to be found in successive episodes. However, the moderate correlations of the symptoms across two depressive recurrences suggested that clinical presentations in bipolar depression may not be predicted by symptom profiles presented in previous episodes. [ABSTRACT FROM AUTHOR]

Abstract: The pathophysiology of bipolar disorder (BD) includes, among other processes, changes in the neuroplasticity and regulation of apoptosis, which could potentially be influenced by inflammatory mediators such as chemokines. The objectives of this study were to investigate serum chemokine levels in patients with BD and to compare results with those obtained with healthy subjects. Here, serum chemokine levels of 30 euthymic patients with BD type I and 30 healthy volunteers were investigated and compared. The chemokines assessed were CCL2, CCL3, CCL8, CCL 9, CCL10, CCL11, and CCL24. Patients with BD showed significant differences in chemokine levels when compared with healthy subjects. While serum levels of CXCL10 were increased (p =.018), CCL24 levels were lower in bipolar patients (p =.025) when compared with controls. There was no statistical difference in the serum levels of CCL2, CCL3, CCL24, CXCL9, and CXCL11 between patients and controls. The presence of chemokine abnormalities in patients with BD during euthymia suggests that these inflammatory mediators should be further investigated with regard to their potential role as longstanding markers of the disorder. [Copyright &y& Elsevier]

Abstract: Background: The neurobiology of bipolar disorder is not completely understood. Cytokines have received increasing attention as potential mediators of the interaction with immune, neuroendocrine system and specific pathways involved in mood, energy, and activity control. Previous reports have suggested the association of mania and bipolar depression with a proinflammatory state. However, they did not compare cytokine levels in all phases of bipolar disorder. Methods: Sixty-one bipolar patients were recruited for assessment of serum cytokine levels. Of these, 14 were in euthymic state, 23 and 24 were in manic and depressive episodes, respectively. A healthy comparison group included 25 healthy volunteers. Cytokines involved in Th1/Th2 balance, such as TNF-α, IL-2, IL-4, IL-6, IL-10, IFN-γ, were examined by flow cytometry. Results: During mania, proinflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4. Mood symptoms showed a positive correlation with IL-6 and IL-2. Discussion: These findings suggest that mania, and to a less extent, depression are associated with a proinflammatory state. These changes seem to be related to mood state, as changes in cytokine profile were more pronounced during acute episodes than in euthymia. This study provides further support to investigate the immune system as a target for future treatment development. [Copyright &y& Elsevier]

Aim: Several lines of evidence suggest that major depressive disorder is associated with an inflammatory status. Tumor necrosis factor-α has been investigated as a potential molecular target in mood disorders. Tumor necrosis factor-α exerts its activity through binding to specific cell membrane receptors named as TNFR1 and TNFR2. The aim of the present study was to investigate soluble plasma TNFR1 (sTNFR1) and TNFR2 levels (sTNFR2) in major depressive disorder patients. Methods: Female outpatients with major depressive disorder ( n = 30) were compared with a healthy control group ( n = 19). Severity of depressive symptoms was evaluated on Beck Depression Inventory; post-traumatic stress disorder (PTSD) symptoms were evaluated on PTSD Checklist–Civilian Version; and childhood abuse and neglect on the Childhood Trauma Questionnaire. Plasma tumor necrosis factor-α and its soluble receptors were measured by ELISA. Results: Patients had no changes in tumor necrosis factor-α concentrations but did have increased sTNFR1 ( P < 0.001) and sTNFR2 ( P < 0.001) levels compared to controls. Plasma level of sTNFR1 was positively predicted by age (B = 0.25, P = 0.05) and PTSD-like symptoms (B = 0.41, P = 0.002) and plasma levels of sTNFR2 by depression severity (B = 0.67, P < 0.001). Conclusions: Soluble tumor necrosis factor-α receptors could be reliable markers of inflammatory activity in major depression. [ABSTRACT FROM AUTHOR]

Abstract: The pathophysiology of bipolar disorder (BD) is poorly understood. An emerging body of evidence points to impairments in neuroplasticity, cell resilience and neuronal survival as the main neuropathological correlates of BD. It has been suggested that inflammatory cytokines, particularly TNF-α may play a critical role in this process. In the present review we examine the evidence suggesting that TNF-α regulates apoptotic cascades which may be related to neuronal and glial loss in BD. Current evidence suggests that an increase in serum levels of TNF-α takes place during manic and depressive episodes. The present article reviews the therapeutic implications of TNF-α signaling pathways involvement in the pathophysiology of BD. [Copyright &y& Elsevier]

Objective: The purpose of this trial is to investigate the relationship between dietary calcium content and incidence of preeclampsia, comparing diet calcium content in normotensive and preeclampsia patients. Dietary calcium was measured by a dietary interview conducted at the day after delivery. Methods: This is a prospective cross-sectional study involving 1092 patients who delivered at Hospital de Clínicas de Porto Alegre – Brazil. Results: The average diet calcium content in the studied population was 1038 mg. The average calcium intake in the normotensive group was 1057 mg, in chronic hypertension group was 962 mg, in transient hypertension group was 963 mg, in mild preeclampsia was 902 mg and in severe preeclampsia group was 755 mg. The results of this study show that pregnant women who develop severe preeclampsia have a significant lower diet calcium intake when compared to normotensive women (P = 0.018). Conclusion: The results of the present study can provide the foundations for prospective trials, including randomised clinical trials involving only patients with a low content of calcium in their diet. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Neuroendocrine Markers of High Risk of Psychosis: Salivary Testosterone in Adolescent Boys With Prodromal Symptoms," by S. van Rijn et al. in a 2011 issue.

Epidemiological and mechanistic studies support the association between Diabetes Mellitus and mood disorders, such as Major Depressive Disorder and Bipolar Disorder. This association is especially relevant in specific domains of depressive psychopathology, such as disturbances in reward systems and cognitive functions. Several anti-hyperglycemic agents have demonstrated effects on depressive symptoms and cognitive decline and this efficacy is probably the result of an action in shared brain targets between these two groups of conditions. These medications include subcutaneous insulin, intranasal insulin, metformin, and liraglutide. The study of the mechanisms involved in the relationship between Diabetes Mellitus and mood disorders offers a new avenue of investigation, and this understanding can be applied when examining whether antidiabetic agents can be repurposed as antidepressants and mood stabilizers. The objective of this narrative review is to critically appraise the literature surrounding drugs commonly used as anti-hyperglycemic agents and their effects on the brain, while discussing their potential as a new treatment for mental illnesses, and specifically, mood disorders. • Findings on metabolism opened new avenues for repurposing drugs used for the treatment of general illnesses. • Depression and bipolar disorder are associated with the risk of subsequent development of diabetes. • The association between mental illnesses and diabetes opened a new avenue of treatment. [ABSTRACT FROM AUTHOR]

Objective: To compare the mortality risk due to covid-19 with death due to overdose in British Columbia, Canada. The opioid epidemic was declared a public health emergency in 2016.Methods: Mortality risk was calculated in micromorts with covid-19 data for January-October 2020, derived from the BC center for Disease Control, and illicit drug toxicity deaths for January 2010-September 2020, derived from the BC Coroners Service. Age-stratified covid-19 incidence and deaths per 100,000 population and age-stratified illicit drug toxicity death rates per 100,000 population were calculated. A micromort is a unit of risk equivalent to a one-in-a-million chance of death.Results: During the covid-19 pandemic, illicit drug toxicity deaths reached 1.0 micromorts per day, representing an increase of 0.5 micromorts per day relative to 2019 rates. In comparison, covid-19 mortality risk was 0.05 micromorts per day among individuals from the general population living in British Columbia and 21.1 micromorts per day among those infected with covid-19. Covid-related mortality risk was significantly lower among individuals aged <60 years, relative to older adults, whereas drug toxicity-related mortality was highest for individuals aged 30-59 years.Conclusions: The mortality associated with covid-19 is apparent and distributed unevenly across subpopulations. The mortality due to overdose has increased during covid-19 and exceeds mortality due to covid-19. Our results instantiate the triple threat caused by covid-19 (i.e., public health crisis, economic crisis and mental health crisis) and quantitatively highlight the externality of increased mortality due to deaths of despair in response to public health efforts to reduce covid-related mortality. [ABSTRACT FROM AUTHOR]

The article discusses how inequalities in healthcare impact mortality risk of individuals with acute mental ill-health. Side effects of psychotropic medications can also be managed effectively through a combination of behavioral and pharmacological interventions. Wealth, socioeconomic status, access to healthcare, mental illness, and health outcomes are all inextricably linked.

Suicide accounts for approximately 800,000 deaths per year globally. Previous research has shown that intranasal esketamine and intravenous ketamine can rapidly decrease the severity of depressive symptoms and suicidal ideation. However, the majority of clinical trials excluded individuals with moderate to high baseline suicidality scores (e.g., suicidal ideation with plan/intent at the time of recruitment). The current review aims to evaluate the effect of esketamine and ketamine in patients with suicidal ideation at baseline. A systematic search was conducted on EMBASE, PsychInfo and PubMed from inception to July 2020 following the PRISMA guidelines. 15 studies met inclusion criteria. Results from esketamine trials did not demonstrate antisuicidal effects, as between-group differences were not found. Intravenous ketamine appeared to rapidly decrease the severity of suicidal ideation and depressive symptoms in individuals with baseline suicidal ideation, though retrospective studies suggest that these effects may be short-lasting. During the double-blind treatment phases, 2.4% of patients from the treatment groups and 1.5% of patients from control groups attempted suicide, with zero deaths by suicide in both the treatment and control groups during this phase. Based on the overall pooled samples, studies were assessed to be relatively safe, and the continual inclusion of this study population in future clinical trials is encouraged. Future research should aim to assess the longitudinal efficacy of ketamine in patients with baseline suicidality. • IV ketamine is associated with rapid & robust decreases in suicidal ideations. • Esketamine has antidepressant effects in patients with baseline suicidality. • The proportion of suicide attempts and death by suicide during these trials was low. • Future trials should consider including patients with baseline suicidality. [ABSTRACT FROM AUTHOR]

Introduction: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. Materials and Methods: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. Results: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. Discussion: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition. [ABSTRACT FROM AUTHOR]

Introduction: Although the recreational cannabis use is expressive worldwide, the literature about medical potential of cannabis extracts, including its anti-inflammatory properties, remains inconclusive. Methods: We screened all articles, published on the PubMed database, on inflammatory mediators and any information about cannabis use from 1980 to March 2019. Results: Six studies were included, and the main findings were as follows: (i) among healthy volunteers and cannabis users, cannabinoids seemed to decrease the inflammatory response, thus decreasing the immune response, which led to a higher risk of infections; (ii) among patients with multiple sclerosis, cannabinoids seemed to have little impact on the inflammatory markers' levels. Discussion: Although cannabis use can produce immune inflammatory suppression in healthy people, this effect is not robust enough to change inflammatory mediators' levels in situations of highly dysfunctional inflammatory activation. Nevertheless, the impact of cannabinoids in clinical outcomes of these conditions remains to be determined. [ABSTRACT FROM AUTHOR]

Bipolar disorders are a complex group of severe and chronic disorders that includes bipolar I disorder, defined by the presence of a syndromal, manic episode, and bipolar II disorder, defined by the presence of a syndromal, hypomanic episode and a major depressive episode. Bipolar disorders substantially reduce psychosocial functioning and are associated with a loss of approximately 10-20 potential years of life. The mortality gap between populations with bipolar disorders and the general population is principally a result of excess deaths from cardiovascular disease and suicide. Bipolar disorder has a high heritability (approximately 70%). Bipolar disorders share genetic risk alleles with other mental and medical disorders. Bipolar I has a closer genetic association with schizophrenia relative to bipolar II, which has a closer genetic association with major depressive disorder. Although the pathogenesis of bipolar disorders is unknown, implicated processes include disturbances in neuronal-glial plasticity, monoaminergic signalling, inflammatory homoeostasis, cellular metabolic pathways, and mitochondrial function. The high prevalence of childhood maltreatment in people with bipolar disorders and the association between childhood maltreatment and a more complex presentation of bipolar disorder (eg, one including suicidality) highlight the role of adverse environmental exposures on the presentation of bipolar disorders. Although mania defines bipolar I disorder, depressive episodes and symptoms dominate the longitudinal course of, and disproportionately account for morbidity and mortality in, bipolar disorders. Lithium is the gold standard mood-stabilising agent for the treatment of people with bipolar disorders, and has antimanic, antidepressant, and anti-suicide effects. Although antipsychotics are effective in treating mania, few antipsychotics have proven to be effective in bipolar depression. Divalproex and carbamazepine are effective in the treatment of acute mania and lamotrigine is effective at treating and preventing bipolar depression. Antidepressants are widely prescribed for bipolar disorders despite a paucity of compelling evidence for their short-term or long-term efficacy. Moreover, antidepressant prescription in bipolar disorder is associated, in many cases, with mood destabilisation, especially during maintenance treatment. Unfortunately, effective pharmacological treatments for bipolar disorders are not universally available, particularly in low-income and middle-income countries. Targeting medical and psychiatric comorbidity, integrating adjunctive psychosocial treatments, and involving caregivers have been shown to improve health outcomes for people with bipolar disorders. The aim of this Seminar, which is intended mainly for primary care physicians, is to provide an overview of diagnostic, pathogenetic, and treatment considerations in bipolar disorders. Towards the foregoing aim, we review and synthesise evidence on the epidemiology, mechanisms, screening, and treatment of bipolar disorders. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis and management of bipolar disorder (BD) are limited by the absence of available biomarkers. Allostatic load (AL) represents the strain that stress, including the effects of acute phases and inter‐episode chronic mood instability, exerts on interconnected biological systems. This study aimed to operationalize an AL index and explore whether it could be relevant to better characterize BD patients with and without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic dysregulation and functional impairment. Methods: Levels of biomarkers of chronic inflammation (hsCRP and albumin), cardiovascular (systolic/diastolic blood pressure) and metabolic functions (fasting glucose, glycosylated hemoglobin, total cholesterol, LDL, HDL, and triglycerides) were measured in 1072 adult BD outpatients. Patients were classified in two groups (with/without emotional hyper‐reactivity) assessed by the Multidimensional Assessment of Thymic States scale. An Allostatic Load Index for BD (BALLI), comprising six biomarkers, was constructed using data‐driven biomarker selection. Results: BALLI showed 81.1% accuracy with good sensitivity (81%) and specificity (81.2%) for characterizing BD patients presenting emotional hyper‐reactivity, elevated risk of inflammation (increased hsCRP, hypoalbuminemia) and cardiometabolic disturbances (hypertension, hyperglycemia, and hypertriglyceridemia). Patients classified by the BALLI as presenting emotional hyper‐reactivity had significantly lower global and cognitive functioning than those without emotional hyper‐reactivity (P <.0001). Conclusions: A multidimensional approach based on a simple AL score (eg, BALLI) and dimensions of behavior (eg, emotional hyper‐reactivity) alongside mood is clinically relevant. AL index could be a useful tool to detect multisystemic physiological dysregulations in BD patients with/without emotional hyper‐reactivity particularly those at higher risk of immune‐cardiometabolic disturbances and functional impairment. [ABSTRACT FROM AUTHOR]

• 60 adults with bipolar depression and baseline inflammatory activation were included. • Infliximab, relative to placebo, significantly reduced anhedonic symptoms. • Anti-anhedonic efficacy of infliximab was robust at week 6 and not sustained at week 12. • Baseline plasma concentrations of TNF-a and sTNFR1 moderated anti-anhedonic efficacy. We investigated the efficacy of tumour necrosis factor (TNF)- α antagonist infliximab on a measure of anhedonia amongst individuals with bipolar I/II depression (ClinicalTrials.gov identifier NCT02363738). Adults (ages 18–65) with bipolar I/II disorder currently experiencing a major depressive episode with a higher probability of inflammatory activity (i.e., meeting one or more of the following inflammatory/metabolic criteria: obesity and dyslipidemia/hypertension, daily cigarette smoking, diabetes mellitus, migraine, inflammatory bowel disease, and/or C-reactive protein level of ⩾ 5 mg/L) were enrolled in a double-blind, 12-week clinical trial of adjunctive infliximab (5 mg/kg) and saline control, which were administered at weeks 0, 2, and 6. The primary outcome measure for the present secondary analysis was change in the Snaith-Hamilton Pleasure Scale (SHAPS) total score between placebo- and infliximab-treated subjects from baseline to weeks 6 and 12. Plasma concentrations of TNF- α and soluble TNF receptors (sTNFR) 1 and 2 were assessed at weeks 0, 2, 6, and 12. Sixty eligible adults received treatment with infliximab (n = 29) or placebo (n = 31); 47 subjects completed the study (infliximab: n = 21 , placebo: n = 26). Overall, infliximab-randomized subjects exhibited significantly larger increases in SHAPS total score, denoting greater reductions in anhedonic symptoms, when compared to placebo-randomized subjects (treatment × time interaction effect: χ 2 = 7.15 , df = 2 , p = 0.03). Anti-anhedonic efficacy was moderated by baseline plasma levels of TNF- α and sTNFR1, but not by changes in TNF- α or sTNFR1 concentrations. Baseline and changes in sTNFR2 concentrations did not moderate anti-anhedonic efficacy. Infliximab significantly improved a measure of anhedonia relative to placebo in adults with bipolar I/II depression at week 6; intervention efficacy was not sustained 6 weeks after the final infusion. [ABSTRACT FROM AUTHOR]

Objective: To investigate the prevalence rates of suicidal ideation (SI) and suicide attempts (SA) and their association with substance use in a nationally representative sample of Brazilians. Methods: The Second Brazilian National Alcohol and Drug Survey (II BNADS) is a household crosssectional survey that investigated the consumption of psychotropic drugs and associated risk factors. This national probability sample survey used a multistage cluster design to select 4,607 participants aged 14 or older and had a total response rate of 77%. Illegal drug use, SI and SA were obtained by confidential self-report assessment. Results: SI and SA were reported by 9.9 and 5.4% of the sample, respectively. This prevalence was 20.8 and 12.4% among individuals with alcohol use disorders (AUD), 31.5 and 16.5% among cannabis users and 40.0 and 20.8% among cocaine users. After adjusting for demographic characteristics, tobacco use, family history of suicide and depression, both SI and SA were positively associated with AUD, cannabis and cocaine use. Conclusion: AUD, cannabis and cocaine use were significantly associated with SI and SA, even after the adjustments. Public health initiatives targeting suicide prevention should consider including assessment and management of substance misuse, and therapeutic approaches to substance misuse should include assessment of suicidality. [ABSTRACT FROM AUTHOR]

Objective: There is limited data about the impact of mood disorders treatment guidelines on clinical outcomes. The objective of this study was to investigate the impact of prescribers' adherence to the 2018 Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) treatment guidelines recommendations on the readmission rates of patients hospitalized for mania. Method: A retrospective cohort of all individuals admitted due to acute mania to Kingston General Hospital, Kingston, ON, from January 2018 to July 2021 was included in this study. Patient variables and data regarding index admission and subsequent hospitalizations were extracted from medical records up to December 31, 2021. Treatment regimens were classified as first-line, second-line, noncompliant, or no treatment. We explored the associations between treatment regimens and the risk of readmissions using univariate, multivariate, and survival analysis. Results: We identified 211 hospitalizations related to 165 patients. The mean time-to-readmission was 211.8 days (standard deviation [SD] = 247.1); the 30-day rehospitalization rate was 13.7%, and any rehospitalization rate was 40.3%. Compared to no treatment, only first-line treatments were associated with a statistically significant decreased risk of 30-day readmission (odds ratio [OR] = 0.209; 95% CI, 0.058 to 0.670). The risk of any readmission was reduced by first-line (OR = 0.387; 95% CI, 0.173 to 0.848) and noncompliant regimens (OR = 0.414; 95% CI, 0.174 to 0.982) compared to no treatment. On survival analysis, no treatment group was associated with shorter time-to-readmission (log-rank test, p = 0.014) and increased risk of readmission (hazard ratio = 2.27; 95% CI, 1.30 to 3.96) when compared to first-line medications. Conclusions: Treatment with first-line medications was associated with lower 30-day rehospitalization rates and longer time-to-readmission. Physicians' adherence to treatments with higher-ranked evidence for efficacy, safety, and tolerability may improve bipolar disorder outcomes. [ABSTRACT FROM AUTHOR]

Lithium remains the gold-standard medication for acute and prophylactic treatment of bipolar disorder. Understanding clinicians' practices and patients' experiences, knowledge and attitudes about lithium may improve its clinical use. Online anonymous surveys collected information about clinician's practices and level of confidence in managing lithium and patients' experiences with lithium treatment and information received about benefits and side effects. Knowledge and attitudes regarding lithium were assessed with the Lithium Knowledge Test (LKT) and the Lithium Attitudes Questionnaire (LAQ). Among 201 clinicians, 64.2% endorsed often treating patients with lithium and reported high levels of confidence in assessing and managing lithium. Practices concerning clinical indications, drug titration, and serum levels were guideline-concordant, but compliance with monitoring recommendations was less frequent. Practitioners were interested in receiving more education about lithium. The patients' survey recruited 219 participants with 70.3% being current lithium users. Most patients (68%) found lithium helpful and 71% reported experiencing any kind of side effect. Most responders did not receive information about side effects or other benefits of lithium. Patients with higher scores on the LKT were more likely to have positive attitudes about lithium. Cross-sectional design with predominantly English-speaking participants from Brazil and North America. There is a discrepancy between guidelines, clinician confidence and knowledge of lithium use and practice. A deeper understanding of how to monitor, prevent and manage long-term side effects and which patients are most likely to benefit from lithium may narrow the gap between knowledge and use. • Despite being the gold-standard treatment for bipolar disorder, lithium is still underused. • Clinicians reported good confidence in managing lithium but may not comply with monitoring practices. • Most patients found lithium useful but did not receive enough information about the treatment. • Clinicians and patients are receptive about improving their lithium literacy. [ABSTRACT FROM AUTHOR]

• Childhood maltreatment is an important stressor associated with stress & depression. • Stress- and depression-associated changes were mostly found in NRC31 and SLCA4. • Epigenetic changes occurring at different loci may have variable downstream effects. • Most studies measured epigenetic changes using peripheral tissue samples. • Future studies should evaluate epigenetic effects of psychotropic medication use. Environmental stressors, such as childhood maltreatment, have been recognized to contribute to the development of depression. Growing evidence suggests that epigenetic changes are a key mechanism by which stressors interact with the genome leading to stable changes in DNA structure, gene expression, and behaviour. The current review aimed to evaluate the relationship between stress-associated epigenetic changes and depression. Human studies were identified via systematic searching of PubMed/Medline from inception to February 2018. Seventeen articles were identified. Stress-associated epigenetic changes in the following genes were correlated with depression: NRC31, SLCA4, BDNF, FKBP5, SKA2, OXTR , LINGO3, POU3F1 and ITGB1. Epigenetic changes in glucocorticoid signaling (e.g., NR3C1, FKBP5), serotonergic signaling (e.g. SLC6A4), and neurotrophin (e.g., BDNF) genes appear to be the most promising therapeutic targets for future research. However, continued research is warranted due to inconsistent findings regarding the directionality of epigenetic modification. Future studies should also aim to control for the use of psychotropic agents due to their widespread use in depressed populations and established effects on DNA methylation. [ABSTRACT FROM AUTHOR]

Aim: We sought to compare alterations in serum bioenergetic markers within a well‐characterized sample of adults with schizophrenia at baseline and after 8 weeks of pharmacological treatment with the hypothesis that treatment would be associated with significant changes in bioenergetic markers given the role of bioenergetic dysfunction in schizophrenia. Methods: We recruited adults with schizophrenia (n = 122) who had not received pharmacological treatment for at least 1 month prior to enrollment, including drug‐naïve (i.e., first‐episode) participants and treatment non‐adherent participants. Pre‐ and post‐treatment serum samples were analyzed using liquid chromatography–tandem mass spectrometry. Results: Metabolites with the greatest change, when comparing pre‐ and post‐treatment levels, were identified revealing 14 water‐soluble metabolites of interest. The composition of these metabolites was: amino acids (n = 6), carnitines (n = 4), polar lipids (n = 3), and organic acid (n = 1). All amino acids and lysophosphatidylcholines (LysoPC) were increased, while the four carnitines – oleoylcarnitine, L‐palmitoylcarnitine, linoleyl carnitine, and L‐acetylcarnitine – were decreased post‐treatment. Of these metabolite biomarkers, six – oleoylcarnitine, linoleyl carnitine, L‐acetylcarnitine, LysoPC(15:0), D‐glutamic acid, and L‐arginine – were identified as having most consistently and predictably changed after 8 weeks of treatment. Conclusion: The current study identified several bioenergetic markers that consistently change with pharmacological treatment. These bioenergetic changes may provide further insights into the pathophysiology of schizophrenia along with furthering our understanding of the mechanisms subserving both the effects (e.g., antipsychotic effects) and side‐effects (e.g., metabolic syndrome) of antipsychotics. [ABSTRACT FROM AUTHOR]

Highlights • Based on the HILIC LC-MS platform, our pilot study analyzed the association between the levels of five N -acetyl derivatives and schizophrenia. • Higher levels of N -acetyl-glutamine were found in first-episode patients with schizophrenia compared to HC in our study. • Decreased N6 -acetyl- L -lysine in first-episode patients with schizophrenia were found compared to HC. • The findings may prove useful in identifying novel disease markers and/or drug target molecules in schizophrenia. Abstract N- acetyl group metabolites are a general class of endogenous compounds characterized by a conjugated system consisting of an acetyl group and nitrogen moiety. The aim of our exploratory pilot case-control study is to compare the levels of five N- acetyl derivatives (i.e., N- acetyl-glutamine, N- acetyl-ornithine, N 6-acetyl- L -lysine, N- acetyl-putrescine, and N- acetyl-galactosamine) in serum samples between individuals with first-episode schizophrenia and healthy controls (HC). A 1:2 age- and sex- matched pilot case-control study was performed, involving 30 cases of first-episode schizophrenia and 60 HC aged between 18 and 40 years old. The serum samples containing these N- acetyl derivatives from (first-episode patients with schizophrenia and HC were measured using liquid chromatography-tandem mass spectrometry (LC-MS). Results indicated that higher levels of N- acetyl-glutamine and lower levels of N 6-acetyl- L -lysine may have a significant association with schizophrenia after adjusting for age, sex and BMI. N- acetyl-putrescine was elevated among subjects with first-episode schizophrenia when compared to HC, suggesting it as a predictor for schizophrenia onset. Further exploration of the mechanisms of N- acetyl group metabolites with respect to schizophrenia is warranted and may be useful for identifying novel disease markers and/or drug target molecules in schizophrenia. [ABSTRACT FROM AUTHOR]

Background Despite the widespread use of antidepressants in clinical practice, the current trial-and-error approach to medication selection contributes to treatment failure and underscores the need to identify reliable predictors of antidepressant response. Since changes in measures of cognition have been reported to occur early in treatment and prior to improvements in overall mood symptoms, the present review aims to determine whether early changes in measures of cognition can predict response in individuals with MDD. Methods A systematic review of studies evaluating early cognitive change as a predictor of later treatment response in MDD was conducted using PubMed/Medline, Embase and PsychINFO. Results A total of seven articles were identified. The available evidence suggests the early changes in cognition may predict treatment response in individuals with MDD. This was shown across antidepressant classes (i.e., SSRIs, SNRIs, NRIs, melatonergic antidepressants) and forms of therapy (i.e., pharmacotherapy, rTMS). The results depict an emerging trend towards early changes in facial emotion recognition (i.e., a hot cognitive process) as a predictor of treatment outcome. Limitations Our qualitative analysis reflects a very limited number of studies. Moreover, there was significant heterogeneity in the evaluation of cognition across studies. Future research should aim to parse out this heterogeneity by evaluating the relative predictive value of different measures of cognition. Conclusion The identification of reliable early treatment predictors of antidepressant response would be clinically significant, enabling clinicians to more accurately evaluate the efficacy of selected treatment avenues. [ABSTRACT FROM AUTHOR]