Although specific risk factors for brain alterations in bipolar disorders (BD) are currently unknown, obesity impacts the brain and is highly prevalent in BD. Gray matter correlates of obesity in BD have been well documented, but we know much less about brain white matter abnormalities in people who have both obesity and BD. We obtained body mass index (BMI) and diffusion tensor imaging derived fractional anisotropy (FA) from 22 white matter tracts in 899 individuals with BD, and 1287 control individuals from 20 cohorts in the ENIGMA-BD working group. In a mega-analysis, we investigated the associations between BMI, diagnosis or medication and FA. Lower FA was associated with both BD and BMI in six white matter tracts, including the corpus callosum and thalamic radiation. Higher BMI or BD were uniquely associated with lower FA in three and six white matter tracts, respectively. People not receiving lithium treatment had a greater negative association between FA and BMI than people treated with lithium in the posterior thalamic radiation and sagittal stratum. In three tracts BMI accounted for 10.5 to 17% of the negative association between the number of medication classes other than lithium and FA. Both overweight/obesity and BD demonstrated lower FA in some of the same regions. People prescribed lithium had a weaker association between BMI and FA than people not on lithium. In contrast, greater weight contributed to the negative associations between medications and FA. Obesity may add to brain alterations in BD and may play a role in effects of medications on the brain.
- MeSH
- anizotropie MeSH
- bílá hmota * patologie diagnostické zobrazování metabolismus MeSH
- bipolární porucha * patologie metabolismus MeSH
- dospělí MeSH
- index tělesné hmotnosti MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozek patologie MeSH
- obezita * patologie metabolismus komplikace MeSH
- šedá hmota MeSH
- zobrazování difuzních tenzorů metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Cardiometabolic risk factors - including diabetes, hypertension, and obesity - have long been linked with adverse health outcomes such as strokes, but more subtle brain changes in regional brain volumes and cortical thickness associated with these risk factors are less understood. Computer models can now be used to estimate brain age based on structural magnetic resonance imaging data, and subtle brain changes related to cardiometabolic risk factors may manifest as an older-appearing brain in prediction models; thus, we sought to investigate the relationship between cardiometabolic risk factors and machine learning-predicted brain age. METHODS: We performed a systematic search of PubMed and Scopus. We used the brain age gap, which represents the difference between one's predicted and chronological age, as an index of brain structural integrity. We calculated the Cohen d statistic for mean differences in the brain age gap of people with and without diabetes, hypertension, or obesity and performed random effects meta-analyses. RESULTS: We identified 185 studies, of which 14 met inclusion criteria. Among the 3 cardiometabolic risk factors, diabetes had the highest effect size (12 study samples; d = 0.275, 95% confidence interval [CI] 0.198-0.352; n = 47 436), followed by hypertension (10 study samples; d = 0.113, 95% CI 0.063-0.162; n = 45 102) and obesity (5 study samples; d = 0.112, 95% CI 0.037-0.187; n = 15 678). These effects remained significant in sensitivity analyses that included only studies that controlled for confounding effects of the other cardiometabolic risk factors. LIMITATIONS: Our study tested effect sizes of only categorically defined cardiometabolic risk factors and is limited by inconsistencies in diabetes classification, a smaller pooled sample in the obesity analysis, and limited age range reporting. CONCLUSION: Our findings show that each of the cardiometabolic risk factors uniquely contributes to brain structure, as captured by brain age. The effect size for diabetes was more than 2 times greater than the independent effects of hypertension and obesity. We therefore highlight diabetes as a primary target for the prevention of brain structural changes that may lead to cognitive decline and dementia.
- MeSH
- diabetes mellitus * epidemiologie patologie MeSH
- hypertenze * epidemiologie patologie MeSH
- kardiometabolické riziko * MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mozek * diagnostické zobrazování patologie MeSH
- obezita * epidemiologie patologie MeSH
- stárnutí patologie MeSH
- strojové učení MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Multidimensional chromatography offers enhanced chromatographic resolution and peak capacity, which are crucial for analyzing complex samples. This study presents a novel comprehensive online multidimensional chromatography method for the lipidomic analysis of biological samples, combining lipid class and lipid species separation approaches. The method combines optimized reversed-phase ultrahigh-performance liquid chromatography (RP-UHPLC) in the first dimension, utilizing a 150 mm long C18 column, with ultrahigh-performance supercritical fluid chromatography (UHPSFC) in the second dimension, using a 10 mm long silica column, both with sub-2 μm particles. A key advantage of employing UHPSFC in the second dimension is its ability to perform ultrafast analysis using gradient elution with a sampling time of 0.55 min. This approach offers a significant increase in the peak capacity. Compared to our routinely used 1D methods, the peak capacity of the 4D system is 10 times higher than RP-UHPLC and 18 times higher than UHPSFC. The entire chromatographic system is coupled with a high-resolution quadrupole-time-of-flight (QTOF) mass analyzer using electrospray ionization (ESI) in both full-scan and tandem mass spectrometry (MS/MS) and with positive- and negative-ion polarities, enabling the detailed characterization of the lipidome. The confident identification of lipid species is achieved through characteristic ions in both polarity modes, information from MS elevated energy (MSE) and fast data-dependent analysis scans, and mass accuracy below 5 ppm. This analytical method has been used to characterize the lipidomic profile of the total lipid extract from human plasma, which has led to the identification of 298 lipid species from 16 lipid subclasses.
- MeSH
- lidé MeSH
- lipidomika * metody MeSH
- lipidy * analýza MeSH
- superkritická fluidní chromatografie metody MeSH
- tandemová hmotnostní spektrometrie * metody MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- lipidy * 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.
- Klíčová slova
- antipsychotics, polypharmacy, predictor, schizophrenia, weight gain,
- 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
- Názvy látek
- antipsychotika * MeSH
- olanzapin MeSH
- risperidon MeSH
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.
- Klíčová slova
- MRI, bipolar disorder, body mass index, obesity, principal component analysis, psychiatry,
- 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
Peatlands store a large proportion of global soil carbon in the form of peat because decomposition of plant organic matter is slow. In Sphagnum-dominated peatlands, dissolved organic matter (DOM) is traditionally considered an important inhibitor of hydrolytic enzymes due to the polyphenolic polymers it contains. Interestingly, the acidic character of the polymers in such DOM has never been tested for its enzyme-inhibitory properties. We raised two principal hypotheses: (1) not only the polyphenolic but also the acidic character of DOM inhibits the activity of extracellular enzymes in Sphagnum-dominated peatlands; (2) environmental, peat-extracted enzymes will show adaptation to their environment. We tested the inhibition of commercial acid phosphatase and cellobiohydrolase, and environmental phosphatase and β-glucosidase by following dissolved substances: (1) polyphenol-free polycarboxylates from Sphagnum cell walls, i.e. sphagnan, (2) environmental DOM (peat-DOM) containing polymers of polyphenolic-polycarboxylate nature, (3) tannic acid (carboxyl-free polyphenolic oligomer) and (4) monomeric phenolic acids. Sphagnan strongly inhibited commercial acid phosphatase, to a similar extent as peat-DOM and more strongly than tannic acid and a polycarboxylate from another moss (Leucobryum glaucum). Monomeric phenolic acids were weak inhibitors. Commercial cellobiohydrolase was only partially inhibited by sphagnan or peat-DOM. Environmental phosphatase and β-glucosidase were consistently slightly inhibited by tannic acid, but not by sphagnan or peat-DOM. Inhibition of commercial phosphatase by sphagnan and peat-DOM was counteracted by a polycation chitosan, indicating the electrostatic nature of carboxylate-mediated inhibition. Our results question the polyphenol-mediated enzyme inhibition in Sphagnum-dominated peatlands as (1) the DOM had a strong inhibitory potential due to its polycarboxylates; nevertheless, (2) the peat microbial communities exhibited enzyme resistance to both polyphenol and polycarboxylate polymers in peat-DOM.
- Klíčová slova
- Bog, Enzyme latch, Extracellular enzyme activity, Peat, Phosphatase, Sphagnan,
- MeSH
- celulosa-1,4-beta-cellobiosidasa MeSH
- fosfatasy MeSH
- kyselá fosfatasa MeSH
- kyseliny MeSH
- polyfenoly MeSH
- polymery MeSH
- půda MeSH
- rašeliníky * MeSH
- rozpuštěná organická hmota MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- celulosa-1,4-beta-cellobiosidasa MeSH
- fosfatasy MeSH
- kyselá fosfatasa MeSH
- kyseliny MeSH
- polyfenoly MeSH
- polymery MeSH
- půda MeSH
- rozpuštěná organická hmota MeSH
Belowground niche partitioning presents a key mechanism for maintaining species coexistence and diversity. Its importance is currently reinforced by climate change that alters soil hydrological conditions. However, experimental tests examining the magnitude of its change under climate change are scarce. We combined measurements of oxygen stable isotopes to infer plant water-uptake depths and extreme drought manipulation in grasslands. Belowground niche partitioning was evidenced by different water-uptake depths of co-occurring species under ambient and extreme drought conditions despite an increased overlap among species due to a shift to shallower soil layers under drought. A co-occurrence of contrasting strategies related to the change of species water-uptake depth distribution was likely to be key for species to maintain some extent of belowground niche partitioning and could contribute to stabilizing coexistence under drought. Our results suggest that belowground niche partitioning could mitigate negative effects on diversity imposed by extreme drought under future climate.
- Klíčová slova
- belowground niche partitioning, climate change, extreme drought, grasslands, hydrological niche segregation, oxygen stable isotopes, rainout shelter, water-uptake depth,
- MeSH
- klimatické změny MeSH
- období sucha * MeSH
- pastviny MeSH
- půda MeSH
- rostliny * MeSH
- voda MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- půda MeSH
- voda MeSH
BACKGROUND: By 2030, over 50% of individuals living with bipolar disorder (BD) are expected to be aged ≥50 years. However, older age bipolar disorder (OABD) remains understudied. There are limited large-scale prospectively collected data organized in key dimensions capable of addressing several fundamental questions about BD affecting this subgroup of patients. METHODS: We developed initial recommendations for the essential dimensions for OABD data collection, based on (1) a systematic review of measures used in OABD studies, (2) a Delphi consensus of international OABD experts, (3) experience with harmonizing OABD data in the Global Aging & Geriatric Experiments in Bipolar Disorder Database (GAGE-BD, n ≥ 4500 participants), and (4) critical feedback from 34 global experts in geriatric mental health. RESULTS: We identified 15 key dimensions and variables within each that are relevant for the investigation of OABD: (1) demographics, (2) core symptoms of depression and (3) mania, (4) cognition screening and subjective cognitive function, (5) elements for BD diagnosis, (6) descriptors of course of illness, (7) treatment, (8) suicidality, (9) current medication, (10) psychiatric comorbidity, (11) psychotic symptoms, (12) general medical comorbidities, (13) functioning, (14) family history, and (15) other. We also recommend particular instruments for capturing some of the dimensions and variables. CONCLUSION: The essential data dimensions we present should be of use to guide future international data collection in OABD and clinical practice. In the longer term, we aim to establish a prospective consortium using this core set of dimensions and associated variables to answer research questions relevant to OABD.
- Klíčová slova
- international collaboration, older age bipolar disorder, prospective studies,
- MeSH
- bipolární porucha * diagnóza epidemiologie terapie MeSH
- kognice MeSH
- lidé MeSH
- prospektivní studie MeSH
- sběr dat MeSH
- senioři MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- stárnutí psychologie MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact. METHODS: We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations. RESULTS: BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI. CONCLUSIONS: We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
- Klíčová slova
- Body mass index, antipsychotics, bipolar disorders, cortical thickness, heterogeneity, lithium, obesity, surface area,
- MeSH
- bipolární porucha * patologie diagnostické zobrazování MeSH
- dospělí MeSH
- index tělesné hmotnosti * MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mozková kůra * diagnostické zobrazování patologie MeSH
- obezita * patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
