"103703" Dotaz Zobrazit nápovědu
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 30 cm
Víceúčelová průřezová sérologická studie populace ČR s cílem hodnocení a monitorování celostátních očkovacích akcí,přesnějšího odhadu postižení populace závažnými infekcemi a sledování měnících se vlastností jednotlivých infekcí.
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- alergologie a imunologie
- parazitologie
- infekční lékařství
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.
- MeSH
- analýza hlavních komponent * MeSH
- bipolární porucha * diagnostické zobrazování farmakoterapie patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * metody MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování patologie MeSH
- mozková kůra diagnostické zobrazování patologie MeSH
- obezita * diagnostické zobrazování MeSH
- schizofrenie diagnostické zobrazování patologie farmakoterapie patofyziologie MeSH
- shluková analýza MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The hippocampus consists of anatomically and functionally distinct subfields that may be differentially involved in the pathophysiology of bipolar disorder (BD). Here we, the Enhancing NeuroImaging Genetics through Meta-Analysis Bipolar Disorder workinggroup, study hippocampal subfield volumetry in BD. T1-weighted magnetic resonance imaging scans from 4,698 individuals (BD = 1,472, healthy controls [HC] = 3,226) from 23 sites worldwide were processed with FreeSurfer. We used linear mixed-effects models and mega-analysis to investigate differences in hippocampal subfield volumes between BD and HC, followed by analyses of clinical characteristics and medication use. BD showed significantly smaller volumes of the whole hippocampus (Cohen's d = -0.20), cornu ammonis (CA)1 (d = -0.18), CA2/3 (d = -0.11), CA4 (d = -0.19), molecular layer (d = -0.21), granule cell layer of dentate gyrus (d = -0.21), hippocampal tail (d = -0.10), subiculum (d = -0.15), presubiculum (d = -0.18), and hippocampal amygdala transition area (d = -0.17) compared to HC. Lithium users did not show volume differences compared to HC, while non-users did. Antipsychotics or antiepileptic use was associated with smaller volumes. In this largest study of hippocampal subfields in BD to date, we show widespread reductions in nine of 12 subfields studied. The associations were modulated by medication use and specifically the lack of differences between lithium users and HC supports a possible protective role of lithium in BD.
- MeSH
- bipolární porucha diagnostické zobrazování farmakoterapie patologie MeSH
- genetika MeSH
- hipokampus diagnostické zobrazování účinky léků patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- neurozobrazování * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
First-degree relatives of patients diagnosed with schizophrenia (SZ-FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First-degree relatives of patients diagnosed with bipolar disorder (BD-FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD-FDRs are inconsistent. Here, we performed a meta-analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ-FDRs, 867 BD-FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ-FDRs showed a pattern of widespread thinner cortex, while BD-FDRs had widespread larger cortical surface area. IQ was lower in SZ-FDRs (d = -0.42, p = 3 × 10-5 ), with weak evidence of IQ reductions among BD-FDRs (d = -0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group-effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ-FDRs and more pronounced effects in BD-FDRs. To conclude, SZ-FDRs and BD-FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ-FDRs and BD-FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment.
- MeSH
- bipolární porucha komplikace diagnostické zobrazování patologie MeSH
- genetická predispozice k nemoci * MeSH
- inteligence fyziologie MeSH
- kognitivní dysfunkce diagnostické zobrazování patologie MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- neurozobrazování * MeSH
- rodina MeSH
- schizofrenie komplikace diagnostické zobrazování etiologie patologie MeSH
- stupeň vzdělání * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive. Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.
OBJECTIVES: The International Society for Bipolar Disorders Big Data Task Force assembled leading researchers in the field of bipolar disorder (BD), machine learning, and big data with extensive experience to evaluate the rationale of machine learning and big data analytics strategies for BD. METHOD: A task force was convened to examine and integrate findings from the scientific literature related to machine learning and big data based studies to clarify terminology and to describe challenges and potential applications in the field of BD. We also systematically searched PubMed, Embase, and Web of Science for articles published up to January 2019 that used machine learning in BD. RESULTS: The results suggested that big data analytics has the potential to provide risk calculators to aid in treatment decisions and predict clinical prognosis, including suicidality, for individual patients. This approach can advance diagnosis by enabling discovery of more relevant data-driven phenotypes, as well as by predicting transition to the disorder in high-risk unaffected subjects. We also discuss the most frequent challenges that big data analytics applications can face, such as heterogeneity, lack of external validation and replication of some studies, cost and non-stationary distribution of the data, and lack of appropriate funding. CONCLUSION: Machine learning-based studies, including atheoretical data-driven big data approaches, provide an opportunity to more accurately detect those who are at risk, parse-relevant phenotypes as well as inform treatment selection and prognosis. However, several methodological challenges need to be addressed in order to translate research findings to clinical settings.
- MeSH
- big data * MeSH
- bipolární porucha epidemiologie terapie MeSH
- datové vědy MeSH
- fenotyp MeSH
- hodnocení rizik MeSH
- klinické rozhodování * MeSH
- lidé MeSH
- poradní výbory MeSH
- prognóza MeSH
- sebevražedné myšlenky * MeSH
- strojové učení * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
BACKGROUND: Schizophrenia and bipolar disorder share genetic liability, and some structural brain abnormalities are common to both conditions. First-degree relatives of patients with schizophrenia (FDRs-SZ) show similar brain abnormalities to patients, albeit with smaller effect sizes. Imaging findings in first-degree relatives of patients with bipolar disorder (FDRs-BD) have been inconsistent in the past, but recent studies report regionally greater volumes compared with control subjects. METHODS: We performed a meta-analysis of global and subcortical brain measures of 6008 individuals (1228 FDRs-SZ, 852 FDRs-BD, 2246 control subjects, 1016 patients with schizophrenia, 666 patients with bipolar disorder) from 34 schizophrenia and/or bipolar disorder family cohorts with standardized methods. Analyses were repeated with a correction for intracranial volume (ICV) and for the presence of any psychopathology in the relatives and control subjects. RESULTS: FDRs-BD had significantly larger ICV (d = +0.16, q < .05 corrected), whereas FDRs-SZ showed smaller thalamic volumes than control subjects (d = -0.12, q < .05 corrected). ICV explained the enlargements in the brain measures in FDRs-BD. In FDRs-SZ, after correction for ICV, total brain, cortical gray matter, cerebral white matter, cerebellar gray and white matter, and thalamus volumes were significantly smaller; the cortex was thinner (d < -0.09, q < .05 corrected); and third ventricle was larger (d = +0.15, q < .05 corrected). The findings were not explained by psychopathology in the relatives or control subjects. CONCLUSIONS: Despite shared genetic liability, FDRs-SZ and FDRs-BD show a differential pattern of structural brain abnormalities, specifically a divergent effect in ICV. This may imply that the neurodevelopmental trajectories leading to brain anomalies in schizophrenia or bipolar disorder are distinct.
- MeSH
- bipolární porucha * genetika patologie MeSH
- dospělí MeSH
- genetická predispozice k nemoci * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mozek patologie MeSH
- schizofrenie * genetika patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
- studie na dvojčatech 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
OBJECTIVE: Hippocampal volume decrease associated with illness burden is among the most replicated findings in unipolar depression. The absence of hippocampal volume changes in most studies of individuals with bipolar disorder (BD) may reflect neuroprotective effects of lithium (Li). METHODS: We recruited 17 BD patients from specialized Li clinics, with at least two years of regularly monitored Li treatment (Li group), and compared them to 12 BD participants with < 3 months of lifetime Li exposure and no Li treatment within two years prior to the scanning (non-Li group) and 11 healthy controls. All BD patients had at least 10 years of illness and five episodes. We also recruited 13 Li-naïve, young BD participants (15-30 years of age) and 18 sex- and age-matched healthy controls. We compared hippocampal volumes obtained from 1.5-T magnetic resonance imaging (MRI) scans using optimized voxel-based morphometry with small volume correction. RESULTS: The non-Li group had smaller left hippocampal volumes than controls (corrected p < 0.05), with a trend for lower volumes than the Li group (corrected p < 0.1), which did not differ from controls. Young, Li-naïve BD patients close to the typical age of onset had comparable hippocampal volumes to controls. CONCLUSIONS: Whereas patients with limited lifetime Li exposure had significantly lower hippocampal volumes than controls, patients with comparable illness burden, but with over two years of Li treatment, or young Li-naïve BD patients, showed hippocampal volumes comparable to controls. These results provide indirect support for neuroprotective effects of Li and negative effects of illness burden on hippocampal volumes in bipolar disorders.
- MeSH
- analýza rozptylu MeSH
- antimanika farmakologie terapeutické užití MeSH
- bipolární porucha * farmakoterapie patologie psychologie MeSH
- chlorid lithný farmakologie terapeutické užití MeSH
- dospělí MeSH
- hipokampus účinky léků patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- osobní újma zaviněná nemocí * MeSH
- psychiatrické posuzovací škály MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Kanada MeSH