Abstract Objective Social cognitive deficits can contribute to risk for depression and to psychosocial impairment during depression. However, available evidence suggests that emotion recognition is ...only marginally impaired in major depressive disorder (MDD). Recent studies have investigated theory of mind (ToM) abilities, a cognitively more demanding aspect of social cognition. Methods We conducted a meta-analysis of studies comparing ToM abilities in MDD and healthy controls. 18 studies comparing 613 patients with MDD and 529 healthy controls were included. Results MDD patients significantly underperformed healthy controls in ToM ( d =0.51–0.58). ToM impairment in MDD was evident in response to different types of ToM tasks (verbal/visual and cognitive/affective and reasoning/decoding). ToM impairment was significantly related to severity of depressive symptoms. Conclusion Theory of mind abilities are impaired during depression and can potentially contribute to psychosocial difficulties during depression. There is a need to investigate ToM abilities in different subtypes and stages of depression, especially in remitted patients.
Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses ...include bipolar disorder, multiple sclerosis, Parkinson's disease, schizophrenia, depression, autism, and chronic fatigue syndrome.
While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson's disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.
This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mental illness, including depression, anxiety and bipolar disorder, accounts for a significant proportion of global disability and poses a substantial social, economic and heath burden. Treatment is ...presently dominated by pharmacotherapy, such as antidepressants, and psychotherapy, such as cognitive behavioural therapy; however, such treatments avert less than half of the disease burden, suggesting that additional strategies are needed to prevent and treat mental disorders. There are now consistent mechanistic, observational and interventional data to suggest diet quality may be a modifiable risk factor for mental illness. This review provides an overview of the nutritional psychiatry field. It includes a discussion of the neurobiological mechanisms likely modulated by diet, the use of dietary and nutraceutical interventions in mental disorders, and recommendations for further research. Potential biological pathways related to mental disorders include inflammation, oxidative stress, the gut microbiome, epigenetic modifications and neuroplasticity. Consistent epidemiological evidence, particularly for depression, suggests an association between measures of diet quality and mental health, across multiple populations and age groups; these do not appear to be explained by other demographic, lifestyle factors or reverse causality. Our recently published intervention trial provides preliminary clinical evidence that dietary interventions in clinically diagnosed populations are feasible and can provide significant clinical benefit. Furthermore, nutraceuticals including n-3 fatty acids, folate, S-adenosylmethionine, N-acetyl cysteine and probiotics, among others, are promising avenues for future research. Continued research is now required to investigate the efficacy of intervention studies in large cohorts and within clinically relevant populations, particularly in patients with schizophrenia, bipolar and anxiety disorders.
Summary Bipolar disorder is a recurrent chronic disorder characterised by fluctuations in mood state and energy. It affects more than 1% of the world's population irrespective of nationality, ethnic ...origin, or socioeconomic status. Bipolar disorder is one of the main causes of disability among young people, leading to cognitive and functional impairment and raised mortality, particularly death by suicide. A high prevalence of psychiatric and medical comorbidities is typical in affected individuals. Accurate diagnosis of bipolar disorder is difficult in clinical practice because onset is most commonly a depressive episode and looks similar to unipolar depression. Moreover, there are currently no valid biomarkers for the disorder. Therefore, the role of clinical assessment remains key. Detection of hypomanic periods and longitudinal assessment are crucial to differentiate bipolar disorder from other conditions. Current knowledge of the evolving pharmacological and psychological strategies in bipolar disorder is of utmost importance.
Mitochondria play a critical role in regulating cellular functions including bioenergetics, calcium homeostasis, redox signalling, and apoptotic cell death. Mitochondria are also essential to many ...aspects of neurodevelopment and neuronal functions. However, mitochondrial impairment may affect bioenergetics in the developing brain and alter critical neuronal processes leading to neurodevelopmental abnormalities. Schizophrenia is a chronic and severe neuropsychiatric disorder of neurodevelopmental origin. Immuno-inflammatory pathway is one of the widely appreciated mechanisms that has consistently been implicated in the neurodevelopmental origin of schizophrenia. However, the source of inflammation and the underlying neurobiological mechanisms leading to schizophrenia are yet to be fully ascertained. Recent understanding reveals that perturbation of mitochondrial network dynamics might lead to various nervous system disorders with inflammatory pathologies. Mitochondrial deficit, altered redox balance and chronic low-grade inflammation are evident in schizophrenia. It is hypothesized that oxidative/nitrosative stress responses due to mitochondrial dysfunctions might activate immuno-inflammatory pathways and subsequently lead to neuroprogressive changes in schizophrenia. Herein, we summarise the current understanding of molecular links between mitochondrial dysfunctions and pathogenesis of schizophrenia based on evidence from genomics, proteomics and imaging studies, which together support a role for mitochondrial impairment in the pathogenetic pathways of schizophrenia.
There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N -acetylcysteine (NAC) is emerging as a useful agent in the ...treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N -acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.
N-acetylcysteine (NAC) has been in clinical practice for several decades. It has been used as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication, ...doxorubicin cardiotoxicity, ischemia–reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/AIDS, heavy metal toxicity and psychiatric disorders.
The mechanisms underlying the therapeutic and clinical applications of NAC are complex and still unclear. The present review is focused on the chemistry of NAC and its interactions and functions at the organ, tissue and cellular levels in an attempt to bridge the gap between its recognized biological activities and chemistry.
The antioxidative activity of NAC as of other thiols can be attributed to its fast reactions with OH, NO2, CO3− and thiyl radicals as well as to restitution of impaired targets in vital cellular components. NAC reacts relatively slowly with superoxide, hydrogen-peroxide and peroxynitrite, which cast some doubt on the importance of these reactions under physiological conditions. The uniqueness of NAC is most probably due to efficient reduction of disulfide bonds in proteins thus altering their structures and disrupting their ligand bonding, competition with larger reducing molecules in sterically less accessible spaces, and serving as a precursor of cysteine for GSH synthesis.
The outlined reactions only partially explain the diverse biological effects of NAC, and further studies are required for determining its ability to cross the cell membrane and the blood–brain barrier as well as elucidating its reactions with components of cell signaling pathways.
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•The chemistry of N-acetylcysteine (NAC) is reviewed.•NAC can detoxify oxidizing radicals and bind redox-active metal ions.•NAC is a precursor of cysteine thus maintaining GSH intracellular levels.•NAC can efficiently reduce disulfide bonds in proteins thus altering their structures.•Not all mechanisms underlying the biological activities of NAC are already clear.
It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma ...and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and ...the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.
Multiple lines of evidence demonstrate a positive association between the degree of peripheral immune activation, inflammation and oxidative stress, gray matter atrophy, glucose hypometabolism and cerebral hypoperfusion in illness, such as multiple sclerosis, Parkinson's disease and chronic fatigue syndrome. Most, if not all, of these abnormalities can be explained by a reduction in the numbers and function of astrocytes secondary to peripheral immune activation and inflammation. This is also true of the widespread mitochondrial dysfunction seen in otherwise normal tissue in neuroinflammatory, neurodegenerative and autoimmune diseases and in many patients with disabling, apparently idiopathic, fatigue. Given the strong association between peripheral immune activation and neuroinflammation with the genesis of fatigue the latter group of patients should be examined using FLAIR magnetic resonance imaging (MRI) and tested for the presence of peripheral immune activation.
It is concluded that peripheral inflammation and immune activation, together with the subsequent activation of glial cells and mitochondrial damage, likely account for the severe levels of intractable fatigue and disability seen in many patients with neuroimmune and autoimmune diseases.This would also appear to be the case for many patients afforded a diagnosis of Chronic Fatigue Syndrome.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As more and more researchers are turning to big data for new opportunities of biomedical discoveries, machine learning models, as the backbone of big data analysis, are mentioned more often in ...biomedical journals. However, owing to the inherent complexity of machine learning methods, they are prone to misuse. Because of the flexibility in specifying machine learning models, the results are often insufficiently reported in research articles, hindering reliable assessment of model validity and consistent interpretation of model outputs.
To attain a set of guidelines on the use of machine learning predictive models within clinical settings to make sure the models are correctly applied and sufficiently reported so that true discoveries can be distinguished from random coincidence.
A multidisciplinary panel of machine learning experts, clinicians, and traditional statisticians were interviewed, using an iterative process in accordance with the Delphi method.
The process produced a set of guidelines that consists of (1) a list of reporting items to be included in a research article and (2) a set of practical sequential steps for developing predictive models.
A set of guidelines was generated to enable correct application of machine learning models and consistent reporting of model specifications and results in biomedical research. We believe that such guidelines will accelerate the adoption of big data analysis, particularly with machine learning methods, in the biomedical research community.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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