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

Background: The greater presence of neurodevelopmental antecedants may differentiate schizophrenia from bipolar disorders (BD). Machine learning/pattern recognition allows us to estimate the biological age of the brain from structural magnetic resonance imaging scans (MRI). The discrepancy between brain and chronological age could contribute to early detection and differentiation of BD and schizophrenia. Methods: We estimated brain age in 2 studies focusing on early stages of schizophrenia or BD. In the first study, we recruited 43 participants with first episode of schizophrenia-spectrum disorders (FES) and 43 controls. In the second study, we included 96 offspring of bipolar parents (48 unaffected, 48 affected) and 60 controls. We used relevance vector regression trained on an independent sample of 504 controls to estimate the brain age of study participants from structural MRI. We calculated the brain-age gap estimate (BrainAGE) score by subtracting the chronological age from the brain age. Results: Participants with FES had higher BrainAGE scores than controls (F(1, 83) = 8.79, corrected P = .008, Cohen's d = 0.64). Their brain age was on average 2.64 ± 4.15 years greater than their chronological age (matched t(42) = 4.36, P < .001). In contrast, participants at risk or in the early stages of BD showed comparable BrainAGE scores to controls (F(2,149) = 1.04, corrected P = .70, η2 = 0.01) and comparable brain and chronological age. Conclusions: Early stages of schizophrenia, but not early stages of BD, were associated with advanced BrainAGE scores. Participants with FES showed neurostructural alterations, which made their brains appear 2.64 years older than their chronological age. BrainAGE scores could aid in early differential diagnosis between BD and schizophrenia.

• MeSH
• bipolární porucha diagnostické zobrazování   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• psychotické poruchy diagnostické zobrazování   MeSH
• riziko MeSH
• schizofrenie diagnostické zobrazování   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
• práce podpořená grantem MeSH
• srovnávací studie MeSH

OBJECTIVE: Bipolar disorders increase the risk of dementia and show biological and brain alterations, which resemble accelerated aging. Lithium may counter some of these processes and lower the risk of dementia. However, until now no study has specifically investigated the effects of Li on brain age. METHODS: We acquired structural magnetic resonance imaging scans from 84 participants with bipolar disorders (41 with and 43 without Li treatment) and 45 controls. 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: BrainAGE was significantly greater in non-Li relative to Li or control participants, F(2, 125) = 10.22, p < 0.001, with no differences between the Li treated and control groups. The estimated brain age was significantly higher than the chronological age in the non-Li (4.28 ± 6.33 years, matched t(42) = 4.43, p < 0.001), but not the Li-treated group (0.48 ± 7.60 years, not significant). Even Li-treated participants with partial prophylactic treatment response showed lower BrainAGE than the non-Li group, F(1, 64) = 4.80, p = 0.03. CONCLUSIONS: Bipolar disorders were associated with greater, whereas Li treatment with lower discrepancy between brain and chronological age. These findings support the neuroprotective effects of Li, which were sufficiently pronounced to affect a complex, multivariate measure of brain structure. The association between Li treatment and BrainAGE was independent of long-term thymoprophylactic response and thus may generalize beyond bipolar disorders, to neurodegenerative disorders.

• MeSH
• bipolární porucha diagnostické zobrazování   farmakoterapie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek diagnostické zobrazování   patologie   MeSH
• multivariační analýza MeSH
• neuroprotektivní látky farmakologie   MeSH
• sloučeniny lithia farmakologie   MeSH
• strojové učení MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Maternal mental health problems during pregnancy are associated with altered neurodevelopment in offspring, but the long-term relationship between these prenatal risk factors and offspring brain structure in adulthood remains incompletely understood due to a paucity of longitudinal studies. OBJECTIVE: To evaluate the association between exposure to maternal depression in utero and offspring brain age in the third decade of life, and to evaluate recent stressful life events as potential moderators of this association. DESIGN, SETTING, AND PARTICIPANTS: This cohort study examined the 30-year follow-up of a Czech prenatal birth cohort with a within-participant design neuroimaging component in young adulthood conducted from 1991 to 2022. Participants from the European Longitudinal Study of Pregnancy and Childhood prenatal birth cohort were recruited for 2 magnetic resonance imaging (MRI) follow-ups, one between ages 23 and 24 years (early 20s) and another between ages 28 and 30 years (late 20s). EXPOSURES: Maternal depression during pregnancy; stressful life events in the past year experienced by the young adult offspring. MAIN OUTCOMES AND MEASURES: Gap between estimated neuroanatomical vs chronological age at MRI scan (brain age gap estimation [BrainAGE]) calculated once in participants' early 20s and once in their late 20s, and pace of aging calculated as the differences between BrainAGE at the 2 MRI sessions in young adulthood. RESULTS: A total of 260 individuals participated in the second neuroimaging follow-up (mean [SD] age, 29.5 [0.6] years; 135 [52%] male); MRI data for both time points and a history of maternal depression were available for 110 participants (mean [SD] age, 29.3 [0.6] years; 56 [51%] male). BrainAGE in participants' early 20s was correlated with BrainAGE in their late 20s (r = 0.7, P < .001), and a previously observed association between maternal depression during pregnancy and BrainAGE in their early 20s persisted in their late 20s (adjusted R2 = 0.04; P = .04). However, no association emerged between maternal depression during pregnancy and the pace of aging between the 2 MRI sessions. The stability of the associations between maternal depression during pregnancy and BrainAGE was also supported by the lack of interactions with recent stress. In contrast, more recent stress was associated with greater pace of aging between the 2 MRI sessions, independent of maternal depression (adjusted R2 = 0.09; P = .01). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that maternal depression and recent stress may have independent associations with brain age and the pace of aging, respectively, in young adulthood. Prevention and treatment of depression in pregnant mothers may have long-term implications for offspring brain development.

• MeSH
• deprese * MeSH
• dítě MeSH
• dospělé děti MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• mozek diagnostické zobrazování   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem 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

INTRODUCTION: Both maternal depression problems during pregnancy and prenatal exposure to air pollution have been associated with changes in the brain as well as worse mood and anxiety in the offspring in adulthood. However, it is not clear whether these effects are independent or whether and how they might interact and impact the brain age and mental health of the young adult offspring. METHODS: A total of 202 mother-child dyads from a prenatal birth cohort were assessed for maternal depression during pregnancy through self-report questionnaires administered in the early 90s, exposure to air pollutants (Sulfur dioxide [SO2], nitrogen oxides [NOx], and suspended particle matter [SPM]) during each trimester based on maternal address and air quality data, mental health of the young adult offspring (28-30 years of age; 52% men, all of European ancestry) using self-report questionnaires for depression (Beck Depression Inventory), mood dysregulation (Profile of Mood States), anxiety (State-Trait Anxiety Inventory), and psychotic symptoms (Schizotypal Personality Questionnaire), and brain age, estimated from structural magnetic resonance imaging (MRI) and previously published neuroanatomical age prediction model using cortical thickness maps. The brain age gap estimate (BrainAGE) was computed by subtracting structural brain age from chronological age. Trajectories of exposure to air pollution during pregnancy were assessed using Growth Mixture Modeling. The interactions of prenatal depression and prenatal exposure to air pollutants on adult mental health and BrainAGE were assessed using hierarchical linear regression. RESULTS: We revealed two distinct trajectories of exposure to air pollution during pregnancy: "early exposure," characterized by high exposure during the first trimester, followed by a steady decrease, and "late exposure," characterized by low exposure during the first trimester, followed by a steady increase in the exposure during the subsequent trimesters. Maternal depression during the first half of pregnancy interacted with NOX exposure trajectory, predicting mood dysregulation and schizotypal symptoms in young adults. In addition, maternal depression during the second half of pregnancy interacted with both NOx and SO2 exposure trajectories, respectively, and predicted BrainAGE in young adults. In those with early exposure to NOx, maternal depression during pregnancy was associated with worse mental health and accelerated brain aging in young adulthood. In contrast, in those with early exposure to SO2, maternal depression during pregnancy was associated with slower brain aging in young adulthood. CONCLUSIONS: Our findings provide the first evidence of the combined effects of prenatal exposure to air pollution and maternal depression on mental health outcomes and brain age in young adult offspring. Moreover, they point out the importance of the timing and trajectory of the exposure during prenatal development.

• MeSH
• deprese * chemicky indukované   MeSH
• dospělí MeSH
• duševní zdraví MeSH
• kohortové studie MeSH
• látky znečišťující vzduch škodlivé účinky   toxicita   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek * účinky léků   růst a vývoj   diagnostické zobrazování   MeSH
• stárnutí MeSH
• těhotenství MeSH
• znečištění ovzduší * škodlivé účinky   MeSH
• zpožděný efekt prenatální expozice * chemicky indukované   psychologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články 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

White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.

• MeSH
• anizotropie MeSH
• bílá hmota * diagnostické zobrazování   růst a vývoj   MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladý dospělý MeSH
• mozek * růst a vývoj   diagnostické zobrazování   anatomie a histologie   MeSH
• stárnutí * fyziologie   MeSH
• zobrazování difuzních tenzorů metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• adrenokortikotropní hormon farmakologie   MeSH
• deoxykortikosteron farmakologie   MeSH
• dřeň nadledvin metabolismus   MeSH
• hydrokortison farmakologie   MeSH
• krysa rodu rattus MeSH
• mozek metabolismus   MeSH
• myokard metabolismus   MeSH
• nandrolon farmakologie   MeSH
• noradrenalin metabolismus   MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH