Search

• 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]

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]

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]

• 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]

Diabetes mellitus and mental health disorders create an immense burden on society worldwide. Knowledge of the cellular and biochemical connections linking these two pathologies has broadened and the mechanism for diet-induced shifts in the microbiota has become more refined. However, there remains limited understanding of the mechanism wherein changes in the microbiota affect the development and severity of these diseases and their interconnectedness. This review examines current literature to highlight a potential mechanism that links specific changes in the microbiome to mental health disorders and diabetes mellitus. Novel data indicate that alterations in the abundance and concentration of bacterium in the gut result in an elevated risk for developing mental and metabolic disorders. Through the mechanisms and downstream effects of short-chain fatty acids and the tryptophan metabolizing pathway, the onset of diabetes is shown to directly affect the development of mental health disorders. This paper provides a possible physiological mechanism connecting these two disorders, which could inform future research and policy decisions limiting the global impact of these diseases. • Consistent alterations in gut microbiome homeostasis link diabetes mellitus and mental health disorders. • Dysbiosis impairs short-chain fatty acid synthesis and mediates diabetes and mood disorder pathology and symptoms. • Dysbiosis in diabetes and mental health disorders regulates the 5-hydroxyindole pathway and may worsen disease symptoms. • Supplementation with prebiotics and probiotics may alleviate disease symptoms via gut-mediated mechanisms. [ABSTRACT FROM AUTHOR]

• Research in BD has been hindered by the lack of a unifying disease model • We propose that dysregulated energy expenditure is a primary cause of BD • We review the evidence on the relevance of energy homeostasis for brain function • The behavioral and mechanistic correlates of energy dysregulation are discussed • We propose the phenotypes and longitudinal progression resulting from this process Advances in the understanding and management of bipolar disorder (BD) have been slow to emerge. Despite notable recent developments in neurosciences, our conceptualization of the nature of this mental disorder has not meaningfully progressed. One of the key reasons for this scenario is the continuing lack of a comprehensive disease model. Within the increasing complexity of modern research methods, there is a clear need for an overarching theoretical framework, in which findings are assimilated and predictions are generated. In this review and hypothesis article, we propose such a framework, one in which dysregulated energy expenditure is a primary, sufficient cause for BD. Our proposed model is centered on the disruption of the molecular and cellular network regulating energy production and expenditure, as well its potential secondary adaptations and compensatory mechanisms. We also focus on the putative longitudinal progression of this pathological process, considering its most likely periods for onset, such as critical periods that challenges energy homeostasis (e.g. neurodevelopment, social isolation), and the resulting short and long-term phenotypical manifestations. [ABSTRACT FROM AUTHOR]

• Neuropeptides have the ability to modulate monoaminergic (e.g. dopamine) signaling. • Neuropeptides action is modulated by degrading enzymes as oligopeptidases. • Neuropeptides modulate the response to antipsychotics. • Oligopeptidases are involved in neuronal migration and brain formation. • Oligopeptidases activity is altered in fist-episode psychosis, schizophrenia and bipolar. Schizophrenia (SCZ) is a complex psychiatric disorder with severe impact on patient's livelihood. In the last years, the importance of neuropeptides in SCZ and other CNS disorders has been recognized, mainly due to their ability to modulate the signaling of classical monoaminergic neurotransmitters as dopamine. In addition, a class of enzymes coined as oligopeptidases are able to cleave several of these neuropeptides, and their potential implication in SCZ was also demonstrated. Interestingly, these enzymes are able to play roles as modulators of neuropeptidergic systems, and they were also implicated in neurogenesis, neurite outgrowth, neuron migration, and therefore, in neurodevelopment and brain formation. Altered activity of oligopeptidases in SCZ was described only more recently, suggesting their possible utility as biomarkers for mental disorders diagnosis or treatment response. We provide here an updated and comprehensive review on neuropeptides and oligopeptidases involved in mental disorders, aiming to attract the attention of physicians to the potential of targeting this system for improving the therapy and for understanding the neurobiology underlying mental disorders as SCZ. [ABSTRACT FROM AUTHOR]

According to the “selfish brain” theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise “selfish” due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed. [ABSTRACT FROM AUTHOR]

Highlights: [•] Pathophysiological changes observed in BD converge on a model of premature aging. [•] Individuals with BD present high rates of age related medical illnesses. [•] Dysregulation in immune system and neurotrophins are present in both conditions. [•] Recognition of BD as an accelerated aging disease opens a new avenue of investigation. [Copyright &y& Elsevier]

Highlights: [•] Sleep architecture changes are found in most patients with schizophrenia. [•] These changes are considered an important part of the pathophysiology of the disorder. [•] Sleep changes negatively affect neocortical plasticity and cognition. [•] Sleep abnormalities and circadian misalignment are present on the early stages of schizophrenia. [•] These abnormalities can be explored as possible predictors of developing a psychotic disorder in at-risk populations. [Copyright &y& Elsevier]