• Publikační typ
• abstrakt z konference MeSH

• MeSH
• osobní vzpomínky jako téma MeSH
• psychiatrie * MeSH
• Publikační typ
• biografie MeSH

• O autorovi
• Mohr, Pavel, 1965- Autorita

The critical role of the immune system in brain function and dysfunction is well recognized, yet development of immune therapies for psychiatric diseases has been slow due to concerns about iatrogenic immune deficiencies. These concerns are emphasized by the lack of objective diagnostic tools in psychiatry. A promise to resolve this conundrum lies in the exploitation of extracellular vesicles (EVs) that are physiologically produced or can be synthetized. EVs regulate recipient cell functions and offer potential for EVs-based therapies. Intranasal EVs administration enables the targeting of specific brain regions and functions, thereby facilitating the design of precise treatments for psychiatric diseases. The development of such therapies requires navigating four dynamically interacting networks: neuronal, glial, immune, and EVs. These networks are profoundly influenced by brain fluid distribution. They are crucial for homeostasis, cellular functions, and intercellular communication. Fluid abnormalities, like edema or altered cerebrospinal fluid (CSF) dynamics, disrupt these networks, thereby negatively impacting brain health. A deeper understanding of the above-mentioned four dynamically interacting networks is vital for creating diagnostic biomarker panels to identify distinct patient subsets with similar neuro-behavioral symptoms. Testing the functional pathways of these biomarkers could lead to new therapeutic tools. Regulatory approval will depend on robust preclinical data reflecting progress in these interdisciplinary areas, which could pave the way for the design of innovative and precise treatments. Highly collaborative interdisciplinary teams will be needed to achieve these ambitious goals.

• MeSH
• biologické markery MeSH
• duševní poruchy * terapie   imunologie   metabolismus   MeSH
• extracelulární vezikuly * imunologie   metabolismus   transplantace   MeSH
• individualizovaná medicína * metody   MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• mozek imunologie   metabolismus   MeSH
• neuroglie * metabolismus   imunologie   MeSH
• neurony * metabolismus   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

OBJECTIVE: The clinical diversity of schizophrenia is reflected by structural brain variability. It remains unclear how this variability manifests across different gray and white matter features. In this meta- and mega-analysis, the authors investigated how brain heterogeneity in schizophrenia is distributed across multimodal structural indicators. METHODS: The authors used the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6,037 individuals for a given brain measure. Variability and mean values of cortical thickness, cortical surface area, cortical folding index, subcortical volume, and fractional anisotropy were examined in individuals with schizophrenia and healthy control subjects. RESULTS: Individuals with schizophrenia showed greater variability in cortical thickness, cortical surface area, subcortical volume, and fractional anisotropy within the frontotemporal and subcortical network. This increased structural variability was mainly associated with psychopathological symptom domains, and the schizophrenia group frequently displayed lower mean values in the respective structural measures. Unexpectedly, folding patterns were more uniform in individuals with schizophrenia, particularly in the right caudal anterior cingulate region. The mean folding values of the right caudal anterior cingulate region did not differ between the schizophrenia and healthy control groups, and folding patterns in this region were not associated with disease-related parameters. CONCLUSIONS: In patients with schizophrenia, uniform folding patterns in the right caudal anterior cingulate region contrasted with the multimodal variability in the frontotemporal and subcortical network. While variability in the frontotemporal and subcortical network was associated with disease-related diversity, uniform folding may indicate a less flexible interplay between genetic and environmental factors during neurodevelopment.

• MeSH
• anizotropie MeSH
• bílá hmota patologie   diagnostické zobrazování   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * patologie   diagnostické zobrazování   MeSH
• schizofrenie * patologie   diagnostické zobrazování   MeSH
• šedá hmota patologie   diagnostické zobrazování   MeSH
• zobrazování difuzních tenzorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

BACKGROUND: We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia. METHODS: We recruited 92 participants with first-episode psychosis (FEP, n = 92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors. RESULTS: Most people started treatment with risperidone (n = 57), followed by olanzapine (n = 29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications. CONCLUSIONS: Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

• MeSH
• antipsychotika * terapeutické užití   škodlivé účinky   MeSH
• dospělí MeSH
• hmotnostní přírůstek * účinky léků   MeSH
• hospitalizace * statistika a číselné údaje   MeSH
• index tělesné hmotnosti * MeSH
• lidé MeSH
• mladý dospělý MeSH
• olanzapin terapeutické užití   MeSH
• polypharmacy MeSH
• prospektivní studie MeSH
• psychotické poruchy * farmakoterapie   MeSH
• risperidon terapeutické užití   škodlivé účinky   MeSH
• rizikové faktory MeSH
• schizofrenie * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Enlarged perivascular spaces (EPVS) are increasingly recognized as an MRI detectable feature of neuroinflammatory processes and age-related neurodegenerative changes. Understanding perivascular characteristics in healthy individuals is crucial for their applicability as a reference for pathological changes. Limited data exists on the EPVS load and interhemispheric asymmetry in distribution among young healthy subjects. Despite the known impact of hydration on brain morphometric studies, blood plasma osmolality's effect on EPVS remains unexplored. This study investigated the influence of age, total intracranial volume (TIV), and blood plasma osmolality on EPVS characteristics in 59 healthy adults, each undergoing MRI and osmolality assessment twice within 14.8 months (mean ± 4 months). EPVS analysis was conducted in the centrum semiovale using high-resolution automated segmentation, followed by an optimization algorithm to enhance EPVS segmentation accuracy. Linear Mixed Effects model was used for the statistical analysis, which unveiled significant inter-individual variability in EPVS load and inter-hemispheric asymmetry. EPVS volume increased with age, higher TIV and lower blood plasma osmolality levels. Our findings offer valuable insights into EPVS characteristics among the healthy population, establishing a foundation to further explore age-related and pathological changes.

• MeSH
• dospělí MeSH
• glymfatický systém * diagnostické zobrazování   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie * metody   MeSH
• mladý dospělý MeSH
• mozek * diagnostické zobrazování   patologie   MeSH
• osmolární koncentrace MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

Obezita se často vyskytuje společně se schizofrenií (Sch) a je asociována s podobnými neurostrukturálními a kognitivními poruchami jako Sch. Navrhujeme testovat, zda je obezita rizikovým faktorem pro zhoršení kognitivních/klinických/mozkových parametrů v průběhu času. Účastníci z naší předchozí průřezové studie budou podrobeni následnému diagnostickému rozhovoru, kognitivním testům, MRI skenování, antropometrickým měřením a podají vzorek krve, a to nejméně 1 rok po výchozím testování. Předpokládáme, že Sch a obezita budou každá nezávisle asociována s 1) regionální mozkovou atrofií, 2) poklesem kognitivních funkcí v čase, 3) horší klinickou prognózou Sch. Identifikace obezity jako modifikovatelného rizikového faktoru pro narušení mozkových struktur, zhoršení kognice a klinických parametrů může rozšířit terapeutické možnosti a zlepšit prognózu pacientů se Sch.; Obesity frequently co-occurs with Schizophrenia (Sch) and typically presents with similar neurostructural and cognitive impairments as Sch. We propose to test whether obesity is a risk factor for brain/cognitive/clinical deterioration over time in Sch. Participants from our previous cross sectional study will undergo a follow up diagnostic interview, cognitive testing, MRI scanning, anthropometric measures and will give a blood sample at least 1 year after the baseline testing. We expect that Sch and obesity will be each independently associated with 1) regional brain atrophy, 2) cognitive decline, over time. 3) Among Sch participants, obesity will be associated with worse cumulative clinical outcomes. We will control for known confounders and explore their contribution to the variance in the outcome measures. Identifying obesity as modifiable risk factors for adverse brain/cognitive and clinical outcomes in Sch could expand therapeutic options and improve prognosis.

• Klíčová slova
• prognóza, prognosis, schizofrenie, schizophrenia, obezita, obesity, paměť, memory, hippocampus, hipokampus, konektivita, connectivity, Brain imaging, zobrazování mozku, čelní lalok, frontal lobe, BrainAGE, BrainAGE,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Machine learning can be used to define subtypes of psychiatric conditions based on shared biological foundations of mental disorders. Here we analyzed cross-sectional brain images from 4,222 individuals with schizophrenia and 7038 healthy subjects pooled across 41 international cohorts from the ENIGMA, non-ENIGMA cohorts and public datasets. Using the Subtype and Stage Inference (SuStaIn) algorithm, we identify two distinct neurostructural subgroups by mapping the spatial and temporal 'trajectory' of gray matter change in schizophrenia. Subgroup 1 was characterized by an early cortical-predominant loss with enlarged striatum, whereas subgroup 2 displayed an early subcortical-predominant loss in the hippocampus, striatum and other subcortical regions. We confirmed the reproducibility of the two neurostructural subtypes across various sample sites, including Europe, North America and East Asia. This imaging-based taxonomy holds the potential to identify individuals with shared neurobiological attributes, thereby suggesting the viability of redefining existing disorder constructs based on biological factors.

• MeSH
• algoritmy * MeSH
• dospělí MeSH
• hipokampus diagnostické zobrazování   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• neurozobrazování MeSH
• průřezové studie MeSH
• reprodukovatelnost výsledků MeSH
• schizofrenie * diagnostické zobrazování   patologie   MeSH
• šedá hmota * diagnostické zobrazování   patologie   MeSH
• strojové učení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Severní Amerika MeSH

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15-90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders.

• Publikační typ
• časopisecké články MeSH