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The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (µCAPs) and employed this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain µCAPs with specific activity patterns within the thalamus. Unlike conventional methods, µCAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the µCAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a µCAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was expressed significantly less frequently in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, activity within the auditory-visual cortex and their respective geniculate nuclei was expressed in two different µCAPs. One of these auditory-visual µCAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN + visuo-auditory-thalamus µCAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity, seen here as the specific hyper-occurrence of these circuits with the task-negative brain networks.
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Síndrome de DiGeorge , Trastornos Psicóticos , Esquizofrenia , Humanos , Imagen por Resonancia Magnética , Trastornos Psicóticos/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Tálamo/diagnóstico por imagenRESUMEN
OBJECTIVES: Bipolar disorder (BD) is a highly heritable disorder characterized by emotion dysregulation and recurrent oscillations between mood states. Despite the proven efficacy of early interventions, vulnerability markers in high-risk individuals are still lacking. BD patients present structural alterations of the hippocampus, a pivotal hub of emotion regulation networks composed of multiple subregions with different projections. However, the hippocampal dynamic functional connectivity (dFC) in BD remains unclear. We aim to investigate whether the dFC of hippocampal subdivisions differentiates BD patients, offspring of BD patients (BDoff), and healthy controls (HC); and whether it correlates with symptoms differently between these groups. METHODS: We studied for the first time the dFC of the hippocampus through a cutting-edge micro-co-activation patterns (µCAPs) analysis of resting-state functional MRI data of 97 subjects (26 BD, 18 BDoff, 53 HC). µCAPs allow a data-driven differentiation within the seed region. RESULTS: dFC between the hippocampal body and a somatomotor-µCAP was lower both in BD patients (p-valueFDR:0.00015) and in BDoff (p-valueFDR:0.020) than in HC. Inversely, dFC between the hippocampal head and a limbic-µCAP was higher in BD patients than in HC (p-valueFDR: 0.005). Furthermore, the correlations between a frontoparietal-µCAP and both depression and emotion dysregulation symptoms were significantly higher in BD than HC (p-valueFDR <0.02). CONCLUSION: Overall, we observed alterations of large-scale functional brain networks associated with decreased cognitive control flexibility and disrupted somatomotor, saliency, and emotion processing in BD. Interestingly, BDoff presented an intermediate phenotype between BD and HC, suggesting that dFC of hippocampal subregions might represent a marker of vulnerability to BD.
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Quantitative susceptibility mapping (QSM) is a powerful, non-invasive, magnetic resonance imaging (MRI) technique that relies on measurement of magnetic susceptibility. So far, QSM has been employed mostly to study neurological disorders characterized by iron accumulation, such as Parkinson's and Alzheimer's diseases. Nonetheless, QSM allows mapping key indicators of cardiac disease such as blood oxygenation and myocardial iron content. For this reason, the application of QSM offers an unprecedented opportunity to gain a better understanding of the pathophysiological changes associated with cardiovascular disease and to monitor their evolution and response to treatment. Recent studies on cardiovascular QSM have shown the feasibility of a non-invasive assessment of blood oxygenation, myocardial iron content and myocardial fibre orientation, as well as carotid plaque composition. Significant technical challenges remain, the most evident of which are related to cardiac and respiratory motion, blood flow, chemical shift effects and susceptibility artefacts. Significant work is ongoing to overcome these challenges and integrate the QSM technique into clinical practice in the cardiovascular field.
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Hierro , Imagen por Resonancia Magnética , Encéfalo , Corazón , Humanos , Imagen por Resonancia Magnética/métodos , Valor Predictivo de las PruebasRESUMEN
Chemotherapy with anthracycline-based regimens remains a cornerstone of treatment of many solid and blood tumors but is associated with a significant risk of cardiotoxicity, which can manifest as asymptomatic left ventricular dysfunction or overt heart failure. These effects are typically dose-dependent and cumulative and may require appropriate screening strategies and cardioprotective therapies in order to minimize changes to anticancer regimens or even their discontinuation. Our current understanding of cardiac damage by anthracyclines includes a central role of oxidative stress and inflammation. The identification of these processes through circulating biomarkers or imaging techniques might then be helpful for early diagnosis and risk stratification. Furthermore, therapeutic strategies relieving oxidative stress and inflammation hold promise to prevent heart failure development or at least to mitigate cardiac damage, although further evidence is needed on their efficacy, either alone or as part of combination therapies with neurohormonal antagonists, which are the current adopted standard.
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Antraciclinas , Cardiotoxicidad , Antraciclinas/efectos adversos , Antibióticos Antineoplásicos/efectos adversos , Humanos , Inflamación , Estrés OxidativoRESUMEN
Introduction: People with psychosis spectrum disorders (PSD) face an elevated risk of metabolic syndrome (MetS), which may reduce their life expectancy by nearly 20%. Pinpointing the shared and specific characteristics and clinical implications of MetS in PSD is crucial for designing interventions to reduce this risk, but an up-to-date review on MetS across the psychosis spectrum is lacking. Methods: This narrative review fills this gap by examining the clinical literature on characteristics and implications of MetS in both distinct PSD and transdiagnostically, i.e., across traditional categorical diagnoses, with a focus on psychiatric and cardio-metabolic management. Results: We discuss common and specific characteristics of MetS in PSD, as well as factors contributing to MetS development in PSD patients, including unhealthy lifestyle factors, genetic predisposition, pro-inflammatory state, drugs consumption, antipsychotic medication, and psychotic symptoms. We highlight the importance of early identification and management of cardio-metabolic risk in PSD patients, as well as the existing gaps in the literature, for instance in the screening for MetS in younger PSD patients. We compare hypotheses-generating clinical associations and characteristics of MetS in different PSD, concluding by reviewing the existing recommendations and challenges in screening, monitoring, and managing MetS in PSD. Conclusion: Early identification and management of MetS are crucial to mitigate the long-term cardio-metabolic toll in PSD patients. Interventions should focus on healthy lifestyle and appropriate pharmacological and behavioral interventions. Further translational and clinical research is needed to develop targeted interventions and personalized treatment approaches for this vulnerable population, aiming at improving physical health and overall well-being.
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Introduction: Moyamoya disease (MMD) is a life-threatening condition characterized by stenosis of intracranial arteries. Despite the frequency and the impact of psychiatric symptoms on the long-term prognosis and quality of life of MMD patients, no systematic review on this topic exists. Methods: This systematic review and meta-analysis included 41 studies (29 being case reports), from PubMed, Scopus, Embase until 27/3/2023, on MMD patients exhibiting psychiatric symptoms. Results: Despite a fair average quality of the articles, quantitative synthesis through logistic regression was possible only for case reports, due to heterogeneity between the other studies. Psychosis, the most frequent psychiatric symptom reported in case reports, was more frequent in MMD patients with left hemisphere involvement. Neurological symptoms occurrence increased the odds of MMD diagnosis preceding psychiatric symptoms. Psychiatric symptoms are highly prevalent in MMD patients and are relatively often the only presenting symptoms. Discussion: We discuss the diagnostic, therapeutic, and prognostic implications of recognizing and characterizing specific psychiatric symptoms in MMD, outlining preliminary guidelines for targeted pharmacological and psychotherapeutic interventions. Lastly, we outline future research and clinical perspectives, striving to enhance the oft-overlooked psychiatric care for MMD patients and to ameliorate their long-term outcome. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023406303.
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N-acetyl aspartate (NAA) is a marker of neuronal integrity and metabolism. Deficiency in neuronal plasticity and hypometabolism are implicated in Major Depressive Disorder (MDD) pathophysiology. To test if cerebral NAA concentrations decrease progressively over the MDD course, we conducted a pre-registered meta-analysis of Proton Magnetic Resonance Spectroscopy (1H-MRS) studies comparing NAA concentrations in chronic MDD (n = 1308) and first episode of depression (n = 242) patients to healthy controls (HC, n = 1242). Sixty-two studies were meta-analyzed using a random-effect model for each brain region. NAA concentrations were significantly reduced in chronic MDD compared to HC within the frontal lobe (Hedges' g = -0.330; p = 0.018), the occipital lobe (Hedges' g = -0.677; p = 0.007), thalamus (Hedges' g = -0.673; p = 0.016), and frontal (Hedges' g = -0.471; p = 0.034) and periventricular white matter (Hedges' g = -0.478; p = 0.047). We highlighted a gap of knowledge regarding NAA levels in first episode of depression patients. Sensitivity analyses indicated that antidepressant treatment may reverse NAA alterations in the frontal lobe. We highlighted field strength and correction for voxel grey matter as moderators of NAA levels detection. Future studies should assess NAA alterations in the early stages of the illness and their longitudinal progression.
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Ácido Aspártico , Trastorno Depresivo Mayor , Espectroscopía de Protones por Resonancia Magnética , Humanos , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Lóbulo Occipital/metabolismo , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Frontal/metabolismo , Lóbulo Frontal/diagnóstico por imagen , Enfermedad Crónica , Tálamo/metabolismo , Tálamo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismoRESUMEN
BACKGROUND: Emotion dysregulation (ED), the difficulty in modulating which emotions are felt, and when and how they are expressed or experienced, has been implicated in an array of psychological disorders. Despite potentially different manifestations depending on the disorder, this symptom is emerging as a transdiagnostic construct that can and should be targeted early, given the associations with various maladaptive behaviors as early as childhood and adolescence. As such, our goal was to investigate the psychotherapeutic interventions used to address ED and gauge their effectiveness, safety, and potential mechanisms across various populations. METHODS: This umbrella systematic review, pre-registered under PROSPERO (registration: CRD42023411452), consolidates evidence from systematic reviews and meta-analyses on psychotherapeutic interventions targeting ED, in accordance with PRISMA guidelines. RESULTS: Our synthesis of quantitative and qualitative evidence from 21 systematic reviews (including 11 meta-analyses) points-with moderate overall risk of bias-to the effectiveness of Dialectical Behavior Therapy and Cognitive Behavioral Therapy in reducing ED in a wide range of adult transdiagnostic psychiatric patients and healthy participants. Similar results have emerged in other less extensively researched methods as well. However, results on adolescents and children are sparse, highlighting the need for additional research to tailor these interventions to the unique challenges of ED in younger populations with diverse externalizing and internalizing disorders. CONCLUSIONS: These demonstrated transdiagnostic advantages of psychotherapy for ED underscore the potential for specifically designed interventions that address this issue directly, particularly for high-risk individuals. In these individuals, early interventions targeting transdiagnostic core dimensions may mitigate the emergence of full-blown disorders. Future research on the mediating factors, the durability of intervention effects, and the exploration of understudied interventions and populations may enhance prevention and treatment efficiency, enhancing the quality of life for those affected by varied manifestations of ED.
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Regulación Emocional , Humanos , Regulación Emocional/fisiología , Terapia Cognitivo-Conductual/métodos , Síntomas Afectivos/terapia , Síntomas Afectivos/etiología , Terapia Conductual Dialéctica , Psicoterapia/métodosRESUMEN
Objectives: Approximately one-third of bariatric surgery patients experience weight regain or suboptimal weight loss within five years post-surgery. Pathological eating styles and psychopathological traits (e.g., emotion dysregulation) are recognized as potential hindrances to sustain weight loss efforts and are implicated in obesity development. A comprehensive understanding of these variables and their interplays is still lacking, despite their potential significance in developing more effective clinical interventions for bariatric patients. We investigate the prevalence of and interactions between pathological eating styles and psychopathological traits in this population. Materials and methods: 110 bariatric surgery candidates were characterized using the Binge Eating Scale (BES), Hamilton Depression/Anxiety Scales (HAM-D/A), Barratt Impulsiveness Scale (BIS-11), Experiences in Close Relationships (ECR), Difficulties in Emotion Regulation Scale (DERS). We analyzed these variables with multiple logistic regression analyses and network analysis. Results: Patients with pathological eating styles showed more pronounced anxiety/depressive symptoms and emotion dysregulation. Network analysis revealed strong connections between BES and DERS, with DERS also displaying robust connections with HAM-A/D and ECR scales. DERS and attention impulsivity (BIS-11-A) emerged as the strongest nodes in the network. Discussion: Our findings demonstrate the mediating role of emotion dysregulation between pathological eating styles and psychopathological traits, supporting existing literature on the association between psychopathological traits, insecure attachment styles, and pathological eating behaviors. This research emphasizes the significance of emotion regulation in the complex network of variables contributing to obesity, and its potential impact on bariatric surgery outcomes. Interventions focusing on emotion regulation may thus lead to improved clinical outcomes for bariatric patients.
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Psychotic symptoms are among the most debilitating and challenging presentations of severe psychiatric diseases, such as schizophrenia, schizoaffective, and bipolar disorder. A pathophysiological understanding of intrinsic brain activity underlying psychosis is crucial to improve diagnosis and treatment. While a potential continuum along the psychotic spectrum has been recently described in neuroimaging studies, especially for what concerns absolute and relative amplitude of low-frequency fluctuations (ALFF and fALFF), these efforts have given heterogeneous results. A transdiagnostic meta-analysis of ALFF/fALFF in patients with psychosis compared to healthy controls is currently lacking. Therefore, in this pre-registered systematic review and meta-analysis PubMed, Scopus, and Embase were searched for articles comparing ALFF/fALFF between psychotic patients and healthy controls. A quantitative synthesis of differences in (f)ALFF between patients along the psychotic spectrum and healthy controls was performed with Seed-based d Mapping, adjusting for age, sex, duration of illness, clinical severity. All results were corrected for multiple comparisons by Family-Wise Error rates. While lower ALFF and fALFF were detected in patients with psychosis in comparison to controls, no specific finding survived correction for multiple comparisons. Lack of this correction might explain the discordant findings highlighted in previous literature. Other potential explanations include methodological issues, such as the lack of standardization in pre-processing or analytical procedures among studies. Future research on ALFF/fALFF differences for patients with psychosis should prioritize the replicability of individual studies. Systematic review registration: https://osf.io/, identifier (ycqpz).
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BACKGROUND: Bipolar disorder (BD) is a common affective disorder characterized by recurrent oscillations between mood states and associated with inflammatory diseases and chronic inflammation. However, data on MRI abnormalities in BD and their relationship with inflammation are heterogeneous and no review has recapitulated them. METHODS: In this pre-registered (PROSPERO: CRD42022308461) systematic review we searched Web of Science Core Collection and PubMed for articles correlating functional or structural MRI measures with immune-related markers in BD. RESULTS: We included 23 studies (6 on functional, 16 on structural MRI findings, 1 on both, including 1'233 BD patients). Overall, the quality of the studies included was fair, with a low risk of bias. LIMITATIONS: Heterogeneity in the methods and results of the studies and small sample sizes limit the generalizability of the conclusions. CONCLUSIONS: A qualitative synthesis suggests that the links between immune traits and functional or structural MRI alterations point toward brain areas involved in affective and somatomotor processing, with a trend toward a negative correlation between peripheral inflammatory markers and brain regions volume. We discuss how disentangling the complex relationship between the immune system and MRI alterations in BD may unveil mechanisms underlying symptoms pathophysiology, potentially with quickly translatable diagnostic, prognostic, and therapeutic implications.
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Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastornos del Humor , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Inflamación/diagnóstico por imagen , BiomarcadoresRESUMEN
OBJECTIVES: Bipolar disorder (BD) is a severe, chronic, affective disorder characterized by recurrent switching between mood states, psychomotor and cognitive symptoms, which can linger in euthymic states as residual symptoms. Hippocampal alterations may play a key role in the neural processing of BD symptoms. However, its dynamic functional connectivity (dFC) remains unclear. Therefore, the present study explores hippocampal dFC in relation to BD symptoms. METHODS: We assessed hippocampus-based dFC coactivation patterns (CAPs) on resting-state fMRI data of 25 euthymic BD patients and 25 age- and sex-matched healthy controls (HC). RESULTS: Bilateral hippocampal dFC with somatomotor networks (SMN) was reduced in BD, compared to HC, while at the same time dFC between the left hippocampus and midcingulo-insular salience system (SN) was higher in BD. Correlational analysis between CAPs and clinical scores revealed that dFC between the bilateral hippocampus and the default-like network (DMN) correlated with depression scores in BD. Furthermore, pathological hyperconnectivity between the default mode network (DMN) and SMN and the frontoparietal network (FPN) was modulated by the same depression scores in BD. CONCLUSIONS: Overall, we observed alterations of large-scale functional brain networks associated with decreased flexibility in cognitive control, salience detection, and emotion processing in BD. Additionally, the present study provides new insights on the neural architecture underlying a self-centered perspective on the environment in BD patients. dFC markers may improve detection, treatment, and follow-up of BD patients and of disabling residual depressive symptoms in particular.
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Trastorno Bipolar , Humanos , Depresión/diagnóstico por imagen , Mapeo Encefálico , Encéfalo , Hipocampo/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Psychiatric diseases exact a heavy socioeconomic toll, and it is particularly difficult to identify their risk factors and causative mechanisms due to their multifactorial nature, the limited physiopathological insight, the many confounding factors, and the potential reverse causality between the risk factors and psychiatric diseases. These characteristics make Mendelian randomization (MR) a precious tool for studying these disorders. MR is an analytical method that employs genetic variants linked to a certain risk factor, to assess if an observational association between that risk factor and a health outcome is compatible with a causal relationship. We report the first systematic review of all existing applications and findings of MR in psychiatric disorders, aiming at facilitating the identification of risk factors that may be common to different psychiatric diseases, and paving the way to transdiagnostic MR studies in psychiatry, which are currently lacking. We searched Web of Knowledge, Scopus, and Pubmed databases (until 3 May 2022) for articles on MR in psychiatry. The protocol was preregistered in PROSPERO (CRD42021285647). We included methodological details and results from 50 articles, mainly on schizophrenia, major depression, autism spectrum disorders, and bipolar disorder. While this review shows how MR can offer unique opportunities for unraveling causal links in risk factors and etiological elements of specific psychiatric diseases and transdiagnostically, some methodological flaws in the existing literature limit reliability of results and probably underlie their heterogeneity. We highlight perspectives and recommendations for future works on MR in psychiatry.
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Trastorno Depresivo Mayor , Psiquiatría , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Reproducibilidad de los Resultados , CausalidadRESUMEN
Acute myocardial infarction and ischemic stroke are leading causes of morbidity and mortality worldwide. Although reperfusion therapies have greatly improved the outcomes of patients with these conditions, many patients die or are severely disabled despite complete reperfusion. It is therefore important to identify interventions that can prevent progression to ischemic necrosis and limit ischemia-reperfusion injury. A possible strategy is ischemic conditioning, which consists of inducing ischemia - either in the ischemic organ or in another body site [i.e., remote ischemic conditioning (RIC), e.g., by inflating a cuff around the patient's arm or leg]. The effects of ischemic conditioning have been studied, alone or in combination with revascularization techniques. Based on the timing (before, during, or after ischemia), RIC is classified as pre-, per-/peri-, or post-conditioning, respectively. In this review, we first highlight some pathophysiological and clinical similarities and differences between cardiac and cerebral ischemia. We report evidence that RIC reduces circulating biomarkers of myocardial necrosis, infarct size, and edema, although this effect appears not to translate into a better prognosis. We then review cutting-edge applications of RIC for the treatment of ischemic stroke. We also highlight that, although RIC is a safe procedure that can easily be implemented in hospital and pre-hospital settings, its efficacy in patients with ischemic stroke remains to be proven. We then discuss possible methodological issues of previous studies. We finish by highlighting some perspectives for future research, aimed at increasing the efficacy of ischemic conditioning for improving tissue protection and clinical outcomes, and stratifying myocardial infarction and brain ischemia patients to enhance treatment feasibility.
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Attention-deficit/hyperactivity disorder (ADHD) is a prevalent and serious neurodevelopmental disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Chronic and childhood stress is involved in ADHD development, and ADHD is highly comorbid with anxiety. Similarly, inflammatory diseases and a pro-inflammatory state have been associated with ADHD. However, while several works have studied the relationship between peripheral inflammation and stress in affective disorders such as depression or bipolar disorder, fewer have explored this association in ADHD. In this narrative review we synthetize evidence showing an interplay between stress, anxiety, and immune dysregulation in ADHD, and we discuss the implications of a potential disrupted neuroendocrine stress response in ADHD. Moreover, we highlight confounding factors and limitations of existing studies on this topic and critically debate multidirectional hypotheses that either suggest inflammation, stress, or anxiety as a cause in ADHD pathophysiology or inflammation as a consequence of this disease. Untangling these relationships will have diagnostic, therapeutic and prognostic implications for ADHD patients.
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BACKGROUND: Bias-prone psychiatric interviews remain the mainstay of bipolar disorder (BD) assessment. The development of digital phenotyping promises to improve BD management. We present a systematic review of the evidence about the use of portable digital devices for the identification of BD, BD types and BD mood states and for symptom assessment. METHODS: We searched Web of KnowledgeSM, Scopus ®, IEEE Xplore, and ACM Digital Library databases (until 5/1/2021) for articles evaluating the use of portable/wearable digital devices, such as smartphone apps, wearable sensors, audio and/or visual recordings, and multimodal tools. The protocol is registered in PROSPERO (CRD42020200086). RESULTS: We included 62 studies (2325 BD; 724 healthy controls, HC): 27 using smartphone apps, either for recording self-assessments (n = 10) or for passively gathering metadata (n = 7) or both (n = 10); 15 using wearable sensors for physiological parameters; 17 analysing audio and/or video recordings; 3 using multiple technologies. Two thirds of the included studies applied artificial intelligence (AI)-based approaches. They achieved fair to excellent classification performances. LIMITATIONS: The included studies had small sample sizes and marked heterogeneity. Evidence of overfitting emerged, limiting generalizability. The absence of clear guidelines about reporting classification performances, with no shared standard metrics, makes results hardly interpretable and comparable. CONCLUSIONS: New technologies offer a noteworthy opportunity to BD digital phenotyping with objectivity and high granularity. AI-based models could deliver important support in clinical decision-making. Further research and cooperation between different stakeholders are needed for addressing methodological, ethical and socio-economic considerations.
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Trastorno Bipolar , Dispositivos Electrónicos Vestibles , Inteligencia Artificial , Trastorno Bipolar/diagnóstico , Humanos , Autoevaluación (Psicología)RESUMEN
Inflammation plays an important role in atherosclerosis. Acute coronary syndromes (ACS), and particularly myocardial infarction (MI), are associated with a systemic inflammatory response that may accelerate coronary atherosclerotic processes, leading to plaque destabilization and increased risk of further cardiovascular events. These considerations provide a conceptual framework for the use of anti-inflammatory therapies in patients with chronic coronary syndrome or ACS. Following the diverging results of trials on canakinumab and methotrexate, the Colchicine Cardiovascular Outcomes Trial (COLCOT) and the Low-Dose Colchicine trial-2 (LoDoCo2) have sparked new interest in the perspective of an anti-inflammatory therapy for CAD by showing that colchicine confers a prognostic benefit in patients with a recent MI or CCS, respectively. Colchicine blocks multiple steps of the inflammatory cascade and modulates also platelet function and endothelial activation. It has a better safety profile than canakinumab and is a very inexpensive drug throughout the world. We deemed it useful to reappraise the available literature on colchicine and coronary artery disease to assess the likelihood that it might become part of the therapeutic armamentarium of this condition.
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Síndrome Coronario Agudo , Aterosclerosis , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Aterosclerosis/tratamiento farmacológico , Colchicina , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Humanos , Infarto del Miocardio/tratamiento farmacológicoRESUMEN
Background and Purpose: Ischemic stroke is one of the most common causes of morbidity and mortality and has numerous clinical mimics. Previous studies have suggested a potential role of the tryptophan-serotonin (5-HT)-kynurenine (TSK) axis in ischemic stroke. Studies assessing this axis in the hyperacute phase of ischemic stroke (<4.5 h) are lacking. This prospective study thus evaluates the TSK axis in transient ischemic attack (TIA) and hyperacute ischemic stroke (AIS) patients. Methods: This study included 28 patients (24 AIS and 4 TIA) and 29 controls. The blood and urine samples of patient were collected within 4.5 h of symptoms onset (day 0, D0), then at 24 h and 3 months. Control blood and urine samples were collected once (D0). The TSK axis markers measured were platelet serotonin transporter (SERT) and 5-HT2A receptor (5-HT2AR) densities and platelet, plasma, and urinary 5-HT, plasma and urinary 5-hydroxyindole acetic acid (5-HIAA), and plasma kynurenine and tryptophan (TRP) levels. Results: At D0, patients exhibited a lower (p = 10-5) platelet SERT density, higher (p < 10-6) platelet 5-HT2AR density, higher (p = 10-5) plasma kynurenine/tryptophan (K/T) ratio, and higher urinary 5-HT (p = 0.011) and 5-HIAA (p = 0.003) levels than controls. Conclusions: We observed, for the first time, a hyperacute dysregulation of the serotonergic axis, and hyperacute and long-lasting activation of the tryptophan-kynurenine pathway in brain ischemia.
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Both oxidative stress and inflammation are enhanced in chronic heart failure. Dysfunction of cardiac mitochondria is a hallmark of heart failure and a leading cause of oxidative stress, which in turn exerts detrimental effects on cellular components, including mitochondria themselves, thus generating a vicious circle. Oxidative stress also causes myocardial tissue damage and inflammation, contributing to heart failure progression. Furthermore, a subclinical inflammatory state may be caused by heart failure comorbidities such as obesity, diabetes mellitus or sleep apnoeas. Some markers of both oxidative stress and inflammation are enhanced in chronic heart failure and hold prognostic significance. For all these reasons, antioxidants or anti-inflammatory drugs may represent interesting additional therapies for subjects either at high risk or with established heart failure. Nonetheless, only a few clinical trials on antioxidants have been carried out so far, with several disappointing results except for vitamin C, elamipretide and coenzyme Q10. With regard to anti-inflammatory drugs, only preliminary data on the interleukin-1 antagonist anakinra are currently available. Therefore, a comprehensive, deep understanding of our current knowledge on oxidative stress and inflammation in chronic heart failure is key to providing some suggestions for future research on this topic.