This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.
- MeSH
- Depressive Disorder, Major pathology diagnostic imaging MeSH
- Adult MeSH
- Connectome * MeSH
- Humans MeSH
- Magnetic Resonance Imaging * MeSH
- Young Adult MeSH
- Cerebral Cortex * diagnostic imaging anatomy & histology MeSH
- Nerve Net * diagnostic imaging anatomy & histology MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Major depressive disorder, particularly its treatment-resistant form (TRD), poses significant treatment challenges. Ketamine, an N-methyl-d-aspartate receptor antagonist, has shown promise in rapidly alleviating depressive symptoms by influencing neuroplasticity and glutamatergic modulation, which are thought to influence brain activity complexity. In this placebo-controlled study, we examined the effects of subanesthetic doses of intravenous ketamine on EEG signal complexity in 24 MDD patients, 21 of whom had TRD. Treatment response was defined by a ≥ 33 % reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) after ketamine administration. Patients underwent eyes-closed resting state EEG recording pre-, start-, end- and 24 h post-infusion, analyzed for temporospatial and spatiotemporal Lempel-Ziv complexity (LZCT and LZCS). Results indicated that ketamine significantly increased whole-brain LZCT during infusion compared to placebo (sodium chloride 0.9 %) (16.90 % vs. -4.84 %, 95 % CI 4.29 to 39.18, p = 0.017). Elevated LZCT at end-pre was associated with less short-term symptom improvement the following day. Conversely, lower pretreatment occipital LZCT (0.33 vs. 0.46, 95 % CI 0.007 to 0.26, p = 0.040) predicted a favorable response to ketamine, supported by a logistic regression model with an ROC area of 0.75. No significant changes were observed in LZCS, suggesting limited utility as a biomarker. In conclusion, occipital LZCT could serve as an effective predictive biomarker for ketamine's therapeutic effects in MDD, with implications for patients with TRD. This underscores the potential of EEG complexity measures in stratifying treatment and enhancing our understanding of the neural impacts of ketamine in depressive disorders.
- MeSH
- Excitatory Amino Acid Antagonists * administration & dosage pharmacology MeSH
- Depressive Disorder, Treatment-Resistant * drug therapy physiopathology MeSH
- Depressive Disorder, Major * drug therapy physiopathology MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Electroencephalography * drug effects MeSH
- Ketamine * administration & dosage pharmacology therapeutic use MeSH
- Middle Aged MeSH
- Humans MeSH
- Brain * drug effects physiopathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Controlled Clinical Trial MeSH
Depresivní a úzkostné poruchy představují významnou zátěž pro primární péči, přičemž poptávka po účinné a dobře tolerované léčbě stále roste. Souhrnný článek shrnuje současné poznatky o trazodonu - multifunkčním antidepresivu ze skupiny SARI, které kombinuje inhibici zpětného vychytávání serotoninu s antagonismem receptoru 5 HT2A. Přehled se zaměřuje na farmakodynamiku a farmakokinetiku léčiva, jeho antidepresivní, anxiolytické a sedativní vlastnosti i potenciální neuroprotektivní účinky. Klinická data dokládají srovnatelnou účinnost s SSRI/SNRI v léčbě velké depresivní poruchy a prokazují přínos u generalizované úzkostné poruchy, insomnie a chronické neuropatické bolesti. Nízké dávky (25-100 mg) se využívají ke zlepšení spánku, zatímco antidepresivní účinek vyžaduje titraci na 150-300 mg denně. Díky relativně příznivému profilu sexuálních nežádoucích účinků a nízké anticholinergní aktivitě je trazodon vhodný i pro starší polymorbidní pacienty. Článek diskutuje praktické aspekty preskripce v ordinaci praktického lékaře, možnosti kombinace s dalšími psychofarmaky a upozorňuje na klíčová bezpečnostní rizika, zejména ortostatickou hypotenzi, prodloužení QT intervalu a vzácný priapismus. Správná volba dávky, postupná titrace a edukace pacienta jsou nezbytné pro maximalizaci terapeutického přínosu a minimalizaci rizik této léčby.
Depressive and anxiety disorders represent a significant burden on primary care, and demand for effective and well-tolerated treatments continues to grow. This article summarises current knowledge of trazodone, a multifunctional antidepressant from the SARI group that combines serotonin reuptake inhibition with HT2A receptor 5 antagonism. This review focuses on the pharmacodynamics and pharmacokinetics of the drug, its antidepressant, anxiolytic, and sedative properties as well as its potential neuroprotective effects. Clinical data demonstrate comparable efficacy to SSRI/SNRIs in the treatment of major depressive disorder and demonstrate benefit in generalized anxiety disorder, insomnia, and chronic neuropathic pain. Low doses (25-100 mg) are used to improve sleep, while the antidepressant effect requires titration to 150-300 mg daily. The relatively favourable sexual side effect profile and low anticholinergic activity make trazodone suitable for elderly polymorbid patients. The article discusses the practicalities of prescribing in the general practitioner's office and options for combination with other psychopharmaceuticals. It also highlights key safety risks, particularly orthostatic hypotension, QT interval prolongation, and rare priapism. Proper dose selection, gradual titration, and patient education are essential to maximize the therapeutic benefit and minimize the risks of this treatment.
BACKGROUND: The European Medicines Agency has recommended a series of restrictions on the use of sodium valproate (valproate) following research linking its exposure in utero to adverse congenital and neurodevelopmental effects in offspring. Recent research has highlighted a potential increased risk of neurodevelopmental disorders in children born to males taking valproate prior to conception. Clinicians and patients require guidance regarding suitable alternatives. AIM: To provide an overview of suitable alternatives to valproate in the management of bipolar disorder. METHOD: A narrative review was conducted. Only medications with an established evidence base in managing different phases of bipolar disorder and endorsed within clinical practice guidelines were considered. Eligible guidelines included those (i) where recommendations were informed by a formal guideline development process and (ii) published in English within the last 15 years. REPROTOX® was chosen as the primary information source regarding reproductive safety of alternative medications. RESULTS: Of all second-generation antipsychotics, quetiapine should be considered a first-line alternative to valproate. Lithium has been associated with an increased risk of cardiac malformations, especially Ebstein anomaly, following in utero exposure. However, given its robust efficacy as an antimanic agent and the absolute risk of cardiac abnormalities being low, it's use can still be considered in individuals of child-bearing potential with appropriate monitoring. Carbamazepine treatment should be avoided due to concerns for teratogenicity. Although considered safe in pregnancy, lamotrigine is largely effective at preventing relapse of bipolar depression. Thus, lamotrigine offers limited clinical utility as an alternative to valproate. CONCLUSION: Specific recommendations are made regarding alternatives to valproate in managing bipolar disorder.
- MeSH
- Antimanic Agents * adverse effects therapeutic use MeSH
- Antipsychotic Agents * adverse effects therapeutic use MeSH
- Bipolar Disorder * drug therapy MeSH
- Valproic Acid * adverse effects therapeutic use MeSH
- Humans MeSH
- Disease Management * MeSH
- Pregnancy MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Comparative Study MeSH
- Geographicals
- Europe MeSH
The serotonergic psychedelics psilocybin, LSD and DMT hold great promise for the development of new treatments for psychiatric conditions such as major depressive disorder, addiction and end-of-life anxiety. Previous studies in both animals and humans have confirmed the effects of these drugs on neuronal activity and plasticity. However, the understanding of the mechanisms of action of these substances is limited. Here we show rapid effects of psychedelics on presynaptic properties, using live cell imaging at the level of single synapses in primary rat cortical neurons. Using the genetically encoded reporter of synaptic vesicle fusion synaptopHluorin, we detected a reduced fraction of synaptic vesicles that fused in response to mild or strong electrical stimulation 3-30 min after application of serotonergic psychedelics. These effects were transient and no longer present 24 h after treatment. While DMT only reduced the total recycling pool, LSD and psilocin also reduced the size of the readily releasable vesicle pool. Imaging with the sensors for glutamate, iGluSnFR, and presynaptic calcium, synGCaMP6, showed that while psilocin and DMT increased evoked glutamate release, LSD and psilocin reduced evoked presynaptic calcium levels. Interestingly, psilocin also affected short-term plasticity leading to a depression of responses to paired stimuli. The rapid and drug-specific modulation of glutamatergic neurotransmission described in this study may contribute to distinct anxiolytic and antidepressant properties of serotonergic psychedelics.
- MeSH
- Hallucinogens * pharmacology MeSH
- Rats MeSH
- Cells, Cultured MeSH
- Glutamic Acid * metabolism MeSH
- Lysergic Acid Diethylamide pharmacology MeSH
- Cerebral Cortex * drug effects metabolism cytology MeSH
- Neurons * drug effects metabolism MeSH
- Rats, Sprague-Dawley MeSH
- Psilocybin pharmacology MeSH
- Serotonin Agents pharmacology MeSH
- Synaptic Vesicles drug effects metabolism MeSH
- Tryptamines pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Psychological distress is recognized as an independent risk factor for cardiovascular diseases (CVDs), contributing to increased morbidity and mortality. While eHealth is increasingly used to deliver psychological interventions, their effectiveness for patients with CVDs remains unclear. OBJECTIVE: This meta-analysis aimed to evaluate the effects of eHealth psychological interventions for patients with CVDs. METHODS: Eligible studies were retrieved from 5 databases (Embase, Medline, PubMed, CINAHL, and Cochrane Library), covering the period from database inception to December 2024. Randomized controlled trials (RCTs) investigating the effect of evidence-based psychological eHealth interventions to improve psychosocial well-being and cardiovascular outcomes for people with CVDs were included. The Cochrane Risk of Bias tool (version 2) was used to judge the methodological quality of reviewed studies. RevMan (version 5.3) was used for meta-analysis. RESULTS: A total of 12 RCTs, comprising 2319 participants from 10 countries, were included in the review. The results demonstrated significant alleviation of depressive symptoms for patients receiving psychological eHealth intervention compared to controls (number of paper included in that particular analysis, n=7; standardized mean difference=-0.30, 95% CI -0.47 to -0.14; I2=57%; P<.001). More specifically, in 6 trials where internet-based cognitive behavioral therapy was delivered, a significant alleviation of depressive symptoms was achieved (standardized mean difference=-0.39, 95% CI -0.56 to -0.21; I2=53%; P<.001). There was no significant change in anxiety or quality of life. Synthesis without meta-analysis regarding stress, adverse events, and cardiovascular events showed inconclusive findings. CONCLUSIONS: Psychological eHealth interventions, particularly internet-based cognitive behavioral therapy, can significantly reduce depressive symptoms among patients with CVDs. A multidisciplinary approach is crucial for comprehensively improving psychological and cardiovascular outcomes. Future studies should explore integrating persuasive design features into eHealth and involving mental health professionals for intervention delivery. TRIAL REGISTRATION: PROSPERO CRD42023452276; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023452276.
- MeSH
- Depression therapy MeSH
- Cardiovascular Diseases * psychology therapy MeSH
- Cognitive Behavioral Therapy MeSH
- Humans MeSH
- Randomized Controlled Trials as Topic MeSH
- Telemedicine * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Meta-Analysis MeSH
- Review MeSH
- Systematic Review MeSH
Oxidative stress and chronic inflammation are important drivers in the pathogenesis and progression of many chronic diseases, such as cancers of the breast, kidney, lung, and others, autoimmune diseases (rheumatoid arthritis), cardiovascular diseases (hypertension, atherosclerosis, arrhythmia), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease), mental disorders (depression, schizophrenia, bipolar disorder), gastrointestinal disorders (inflammatory bowel disease, colorectal cancer), and other disorders. With the increasing demand for less toxic and more tolerable therapies, flavonoids have the potential to effectively modulate the responsiveness to conventional therapy and radiotherapy. Flavonoids are polyphenolic compounds found in fruits, vegetables, grains, and plant-derived beverages. Six of the twelve structurally different flavonoid subgroups are of dietary significance and include anthocyanidins (e.g. pelargonidin, cyanidin), flavan-3-ols (e.g. epicatechin, epigallocatechin), flavonols (e.g. quercetin, kaempferol), flavones (e.g. luteolin, baicalein), flavanones (e.g. hesperetin, naringenin), and isoflavones (daidzein, genistein). The health benefits of flavonoids are related to their structural characteristics, such as the number and position of hydroxyl groups and the presence of C2C3 double bonds, which predetermine their ability to chelate metal ions, terminate ROS (e.g. hydroxyl radicals formed by the Fenton reaction), and interact with biological targets to trigger a biological response. Based on these structural characteristics, flavonoids can exert both antioxidant or prooxidant properties, modulate the activity of ROS-scavenging enzymes and the expression and activation of proinflammatory cytokines (e.g., interleukin-1beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), induce apoptosis and autophagy, and target key signaling pathways, such as the nuclear factor erythroid 2-related factor 2 (Nrf2) and Bcl-2 family of proteins. This review aims to briefly discuss the mutually interconnected aspects of oxidative and inflammatory mechanisms, such as lipid peroxidation, protein oxidation, DNA damage, and the mechanism and resolution of inflammation. The major part of this article discusses the role of flavonoids in alleviating oxidative stress and inflammation, two common components of many human diseases. The results of epidemiological studies on flavonoids are also presented.
- MeSH
- Flavonoids * pharmacology chemistry therapeutic use metabolism MeSH
- Humans MeSH
- Neoplasms drug therapy metabolism pathology MeSH
- Neurodegenerative Diseases drug therapy metabolism MeSH
- Oxidative Stress * drug effects MeSH
- Inflammation * drug therapy metabolism pathology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Emočně nestabilní adolescenti představují rozsáhlou skupinu pacientů, kterými se v současnosti zabývají pedopsychiatrická pracoviště, jak ambulantního, tak lůžkového charakteru. Převážnou většinu tvoří adolescentní dívky, které přicházejí zejména pro úzkostně depresivní symptomatiku, sebepoškozování a suicidální chování. Emoční nestabilita v adolescenci představuje spektrum závažnosti, počínaje emoční labilitou obvyklou v dospívání, až po poruchy ve vývoji osobnosti, které mohou v nejzávažnějším případě vyústit do emočně nestabilní – hraniční poruchy osobnosti. Terapie vyžaduje integrovaný přístup, s důrazem na psychoterapii a rodinnou terapii, a také indikovanou farmakoterapii.
Emotionaly unstable adolescents represent a large group of patients currently dealt with pedopsychiatric facilities, both outpatient and inpatient. The vast majority are adolescent girl who come mainly for anxiety - depressive symptoms, self harm and suicidal behavior. Emotional instability in adolescence represents a spektrum of severity, starting with emotional lability common in adolescence, up to disturbances in personality development, which in the most serious case can reset in emotionally unstable - bordeline personality disorder. Therapy requires an integrated approach, with an emphasis on psychotherapy and family therapy, as well as indicated pharmacotherapy.
- MeSH
- Dialectical Behavior Therapy methods MeSH
- Borderline Personality Disorder * epidemiology psychology MeSH
- Humans MeSH
- Adolescent * MeSH
- Suicide, Attempted psychology MeSH
- Psychotherapy methods MeSH
- Self Mutilation MeSH
- Selective Serotonin Reuptake Inhibitors MeSH
- Check Tag
- Humans MeSH
- Adolescent * MeSH
Delayed reperfusion of the ischemic heart (I/R) is known to impair the recovery of cardiac function and produce a wide variety of myocardial defects, including ultrastructural damage, metabolic alterations, subcellular Ca2+-handling abnormalities, activation of proteases, and changes in cardiac gene expression. Although I/R injury has been reported to induce the formation of reactive oxygen species (ROS), inflammation, and intracellular Ca2+ overload, the generation of oxidative stress is considered to play a critical role in the development of cardiac dysfunction. Increases in the production of superoxide, hydroxyl radicals, and oxidants, such as hydrogen peroxide and hypochlorous acid, occur in hearts subjected to I/R injury. In fact, mitochondria are a major source of the excessive production of ROS in I/R hearts due to impairment in the electron transport system as well as activation of xanthine oxidase and NADPH oxidase. Nitric oxide synthase, mainly present in the endothelium, is also activated due to I/R injury, leading to the production of nitric oxide, which, upon combination with superoxide radicals, generates nitrosative stress. Alterations in cardiac function, sarcolemma, sarcoplasmic reticulum Ca2+-handling activities, mitochondrial oxidative phosphorylation, and protease activation due to I/R injury are simulated upon exposing the heart to the oxyradical-generating system (xanthine plus xanthine oxidase) or H2O2. On the other hand, the activation of endogenous antioxidants such as superoxide dismutase, catalase, glutathione peroxidase, and the concentration of a transcription factor (Nrf2), which modulates the expression of various endogenous antioxidants, is depressed due to I/R injury in hearts. Furthermore, pretreatment of hearts with antioxidants such as catalase plus superoxide dismutase, N-acetylcysteine, and mercaptopropionylglycerine has been observed to attenuate I/R-induced subcellular Ca2+ handling and changes in Ca2+-regulatory activities; additionally, it has been found to depress protease activation and improve the recovery of cardiac function. These observations indicate that oxidative stress is intimately involved in the pathological effects of I/R injury and different antioxidants attenuate I/R-induced subcellular alterations and improve the recovery of cardiac function. Thus, we are faced with the task of developing safe and effective antioxidants as well as agents for upregulating the expression of endogenous antioxidants for the therapy of I/R injury.
- Publication type
- Journal Article MeSH
- Review MeSH
Bipolar disorder is a leading contributor to the global burden of disease1. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown2. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.8 million controls), combining clinical, community and self-reported samples. We identified 298 genome-wide significant loci in the multi-ancestry meta-analysis, a fourfold increase over previous findings3, and identified an ancestry-specific association in the East Asian cohort. Integrating results from fine-mapping and other variant-to-gene mapping approaches identified 36 credible genes in the aetiology of bipolar disorder. Genes prioritized through fine-mapping were enriched for ultra-rare damaging missense and protein-truncating variations in cases with bipolar disorder4, highlighting convergence of common and rare variant signals. We report differences in the genetic architecture of bipolar disorder depending on the source of patient ascertainment and on bipolar disorder subtype (type I or type II). Several analyses implicate specific cell types in the pathophysiology of bipolar disorder, including GABAergic interneurons and medium spiny neurons. Together, these analyses provide additional insights into the genetic architecture and biological underpinnings of bipolar disorder.
- MeSH
- Asian People genetics MeSH
- White MeSH
- White People genetics MeSH
- Bipolar Disorder * genetics MeSH
- Genome-Wide Association Study * MeSH
- Black or African American genetics MeSH
- Phenotype * MeSH
- GABAergic Neurons metabolism MeSH
- Genetic Predisposition to Disease MeSH
- Genomics * MeSH
- Hispanic or Latino genetics MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
