The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.

• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• plexus chorioideus * diagnostické zobrazování   patologie   MeSH
• psychotické poruchy * diagnostické zobrazování   patologie   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

5,10-Methylenetetrahydrofolate reductase (MTHFR) deficiency usually presents as a severe neonatal disease. This study aimed to characterize natural history, biological and molecular data, and response to treatment of patients with late-onset MTHFR deficiency. The patients were identified through the European Network and Registry for Homocystinuria and Methylation Defects and the Adult group of the French Society for Inherited Metabolic Diseases; data were retrospectively colleted. To identify juvenile to adult-onset forms of the disease, we included patients with a diagnosis established after the age of 10 years. We included 14 patients (median age at diagnosis: 32 years; range: 11-54). At onset (median age: 20 years; range 9-38), they presented with walking difficulties (n = 8), cognitive decline (n = 3) and/or seizures (n = 3), sometimes associated with mild mental retardation (n = 6). During the disease course, symptoms were almost exclusively neurological with cognitive dysfunction (93%), gait disorders (86%), epilepsy (71%), psychiatric symptoms (57%), polyneuropathy (43%), and visual deficit (43%). Mean diagnostic delay was 14 years. Vascular events were observed in 28% and obesity in 36% of the patients. One patient remained asymptomatic at the age of 55 years. Upon treatment, median total homocysteine decreased (from 183 μmol/L, range 69-266, to 90 μmol/L, range 20-142) and symptoms improved (n = 9) or stabilized (n = 4). Missense pathogenic variants in the C-terminal regulatory domain of the protein were over-represented compared to early-onset cases. Residual MTHFR enzymatic activity in skin fibroblasts (n = 4) was rather high (17%-58%). This series of patients with late-onset MTHFR deficiency underlines the still unmet need of a prompt diagnosis of this treatable disease.

• MeSH
• dítě MeSH
• dospělí MeSH
• epilepsie diagnóza   patologie   MeSH
• homocystinurie diagnóza   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mentální retardace diagnóza   patologie   MeSH
• methylentetrahydrofolátreduktasa (NADPH2) nedostatek   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• opožděná diagnóza MeSH
• psychotické poruchy diagnóza   patologie   MeSH
• retrospektivní studie MeSH
• svalová spasticita diagnóza   patologie   MeSH
• věk při počátku nemoci MeSH
• záchvaty diagnóza   patologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

BACKGROUND: Obesity is highly prevalent in schizophrenia, with implications for psychiatric prognosis, possibly through links between obesity and brain structure. In this longitudinal study in first episode of psychosis (FEP), we used machine learning and structural magnetic resonance imaging (MRI) to study the impact of psychotic illness and obesity on brain ageing/neuroprogression shortly after illness onset. METHODS: We acquired 2 prospective MRI scans on average 1.61 years apart in 183 FEP and 155 control individuals. We used a machine learning model trained on an independent sample of 504 controls to estimate the individual brain ages of study participants and calculated BrainAGE by subtracting chronological from the estimated brain age. RESULTS: Individuals with FEP had a higher initial BrainAGE than controls (3.39 ± 6.36 vs 1.72 ± 5.56 years; β = 1.68, t(336) = 2.59, P = .01), but similar annual rates of brain ageing over time (1.28 ± 2.40 vs 1.07±1.74 estimated years/actual year; t(333) = 0.93, P = .18). Across both cohorts, greater baseline body mass index (BMI) predicted faster brain ageing (β = 0.08, t(333) = 2.59, P = .01). For each additional BMI point, the brain aged by an additional month per year. Worsening of functioning over time (Global Assessment of Functioning; β = -0.04, t(164) = -2.48, P = .01) and increases especially in negative symptoms on the Positive and Negative Syndrome Scale (β = 0.11, t(175) = 3.11, P = .002) were associated with faster brain ageing in FEP. CONCLUSIONS: Brain alterations in psychosis are manifest already during the first episode and over time get worse in those with worsening clinical outcomes or higher baseline BMI. As baseline BMI predicted faster brain ageing, obesity may represent a modifiable risk factor in FEP that is linked with psychiatric outcomes via effects on brain structure.

• MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• longitudinální studie MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita komplikace   diagnostické zobrazování   patologie   patofyziologie   MeSH
• předčasné stárnutí diagnostické zobrazování   etiologie   patologie   patofyziologie   MeSH
• progrese nemoci * MeSH
• psychotické poruchy diagnostické zobrazování   patologie   patofyziologie   MeSH
• rizikové faktory MeSH
• strojové učení * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• amisulprid aplikace a dávkování   terapeutické užití   MeSH
• antipsychotika aplikace a dávkování   terapeutické užití   MeSH
• aripiprazol aplikace a dávkování   terapeutické užití   MeSH
• dospělí MeSH
• flufenazin aplikace a dávkování   terapeutické užití   MeSH
• klozapin aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• paranoidní schizofrenie diagnóza   farmakoterapie   komplikace   MeSH
• psychoterapie MeSH
• psychotické poruchy diagnóza   farmakoterapie   patologie   MeSH
• schizofrenie a poruchy s psychotickými rysy * diagnóza   farmakoterapie   patofyziologie   MeSH
• schizofrenie diagnóza   farmakoterapie   patofyziologie   MeSH
• schizotypální porucha osobnosti diagnóza   farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

• MeSH
• kognitivní poruchy patologie   MeSH
• léčivé přípravky klasifikace   MeSH
• lidé MeSH
• nežádoucí účinky léčiv MeSH
• percepční poruchy patologie   MeSH
• psychotické poruchy * diagnóza   etiologie   komplikace   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVES: Although schizencephaly belongs to the class of neurodevelopmental disorders, which are a well-known predisposing factor for psychosis, there is a lack of relevant studies and diagnostic guidelines on this relationship. METHOD: A case report of first-episode psychosis with persistent negative symptoms associated with schizencephaly is described and compared with 7 other cases found in the literature. RESULTS: We found perinatal pathology, cognitive deficit, and EEG abnormality in a patient with atypical initial symptoms of psychosis such as olfactory hallucinations. Abnormal EEG findings (left frontal spikes and frontal intermittent rhythmic delta activity) called for magnetic resonance imaging, which revealed left parieto-occipital closed-lip schizencephaly. The patient exhibited a partial response to low-dose amisulpride treatment. CONCLUSION: We conclude that schizencephaly in our patient was at first asymptomatic and later developed into clinically manifest schizophrenia-like disorder. Both magnetic resonance imaging and EEG were essential tools for establishing this diagnosis.

• MeSH
• dospělí MeSH
• elektroencefalografie MeSH
• fenotyp MeSH
• lidé MeSH
• mozek patofyziologie   MeSH
• psychotické poruchy komplikace   patologie   patofyziologie   MeSH
• schizencefalie komplikace   patofyziologie   MeSH
• schizofrenie komplikace   patologie   patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

Klozapin je antipsychotikum s unikátními klinickými úèinky. Práce pøináší pøehled literatury, která hodnotí efekt klozapinu na morfologii a funkci jednotlivých bunìèných populací mozku s ohledem na pøedpokládanou neuropatologii schizofrenie. Ukazuje se, že klozapin má jedineèný mechanismus úèinku, který vedle specifického profilu receptorù, s nimiž interaguje, zahrnuje i další vlivy na bunìèné typy centrální nervové soustavy (CNS). Moduluje neuronální funkce, upravuje spolupráci v kortikálních mikrookruzích a funkce astroglie (cyklus glutamátu, trofické procesy). Zlepšuje narušenou cytoarchitekturu kortexu a koriguje synaptickou patologii a arborizaci dendritù neuronù. Dále má neuroprotektivní úèinky, které mohou bránit progresi neuronálního poškození a související klinické deterioraci.

Clozapine is an antipsychotic agent with unique clinical efficacy. This paper presents a review of evidence on clozapine effects on morphology and function of brain cells in the context of neuropathology of schizophrenia. It seems that clozapine exerts a unique mechanism of action that goes beyond the complex pattern of neuroreceptor interactions. It modulates neuronal activity - activates hypoactive and inhibits hyperactive neuronal states - improves cooperation in cortical microcircuits, improves astroglial functions (glu-tamate cycle, trophic processes). It has a potential to restitute abnormal cytoarchitecture, i. e. improve synaptic pathology and reduced dendritic arborization. Moreover, it acts as an neuroprotective agent with subsequent prevention of progressive neuronal damage with clinical deterioration.

• MeSH
• antagonisté dopaminu D2 MeSH
• antagonisté serotoninu MeSH
• antipsychotika farmakologie   MeSH
• astrocyty účinky léků   MeSH
• dopaminergní neurony účinky léků   MeSH
• glutamáty účinky léků   MeSH
• klozapin * farmakologie   terapeutické užití   MeSH
• mikroglie účinky léků   MeSH
• mozková kůra účinky léků   MeSH
• neuroplasticita MeSH
• psychotické poruchy farmakoterapie   patofyziologie   patologie   MeSH
• schizofrenie * farmakoterapie   patologie   MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

• MeSH
• bipolární porucha diagnostické zobrazování   metabolismus   patologie   MeSH
• čelní lalok patologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek patologie   MeSH
• mozková kůra patofyziologie   MeSH
• neurozobrazování MeSH
• prefrontální mozková kůra patologie   MeSH
• psychotické poruchy patologie   MeSH
• šedá hmota patologie   MeSH
• sexuální faktory MeSH
• spánkový lalok patologie   MeSH
• studie případů a kontrol MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

INTRODUCTION: Obesity and dyslipidemia may negatively affect brain health and are frequent medical comorbidities of schizophrenia and related disorders. Despite the high burden of metabolic disorders, little is known about their effects on brain structure in psychosis. We investigated, whether obesity or dyslipidemia contributed to brain alterations in first-episode psychosis (FEP). METHODS: 120 participants with FEP, who were undergoing their first psychiatric hospitalization, had <24 months of untreated psychosis and were 18-35 years old and 114 controls within the same age range participated in the study. We acquired 3T brain structural MRI, fasting lipids and body mass index. We used machine learning trained on an independent sample of 504 controls to estimate the individual brain age of study participants and calculated the BrainAGE score by subtracting the chronological from the estimated brain age. RESULTS: In a multiple regression model, the diagnosis of FEP (B = 1.15, SE B = 0.31, p < 0.001) and obesity/overweight (B = 0.92, SE B = 0.35, p = 0.008) were each additively associated with BrainAGE scores (R2 = 0.22, F(3, 230) = 21.92, p < 0.001). BrainAGE scores were highest in participants with FEP and obesity/overweight (3.83 years, 95%CI = 2.35-5.31) and lowest in normal weight controls (-0.27 years, 95%CI = -1.22-0.69). LDL-cholesterol, HDL-cholesterol or triglycerides were not associated with BrainAGE scores. CONCLUSIONS: Overweight/obesity may be an independent risk factor for diffuse brain alterations manifesting as advanced brain age already early in the course of psychosis. These findings raise the possibility that targeting metabolic health and intervening already at the level of overweight/obesity could slow brain ageing in FEP.

• MeSH
• dospělí MeSH
• dyslipidemie krev   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• nadváha diagnostické zobrazování   epidemiologie   metabolismus   MeSH
• obezita diagnostické zobrazování   epidemiologie   metabolismus   MeSH
• psychotické poruchy diagnostické zobrazování   epidemiologie   patologie   MeSH
• rizikové faktory MeSH
• rozpoznávání automatizované MeSH
• schizofrenie diagnostické zobrazování   epidemiologie   patologie   MeSH
• strojové učení MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• centrální nervový systém patologie   MeSH
• duševní poruchy * patologie   MeSH
• lidé MeSH
• psychotické poruchy patologie   MeSH
• schizofrenie epidemiologie   patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH