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
BACKGROUND: Lateral ventricular enlargement represents a canonical morphometric finding in chronic patients with schizophrenia; however, longitudinal studies elucidating complex dynamic trajectories of ventricular volume change during critical early disease stages are sparse. METHODS: We measured lateral ventricular volumes in 113 first-episode schizophrenia patients (FES) at baseline visit (11.7 months after illness onset, SD = 12.3) and 128 age- and sex-matched healthy controls (HC) using 3T MRI. MRI was then repeated in both FES and HC one year later. RESULTS: Compared to controls, ventricular enlargement was identified in 18.6% of patients with FES (14.1% annual ventricular volume (VV) increase; 95%CI: 5.4; 33.1). The ventricular expansion correlated with the severity of PANSS-negative symptoms at one-year follow-up (p = 0.0078). Nevertheless, 16.8% of FES showed an opposite pattern of statistically significant ventricular shrinkage during ≈ one-year follow-up (-9.5% annual VV decrease; 95%CI: -23.7; -2.4). There were no differences in sex, illness duration, age of onset, duration of untreated psychosis, body mass index, the incidence of Schneiderian symptoms, or cumulative antipsychotic dose among the patient groups exhibiting ventricular enlargement, shrinkage, or no change in VV. CONCLUSION: Both enlargement and ventricular shrinkage are equally present in the early stages of schizophrenia. The newly discovered early reduction of VV in a subgroup of patients emphasizes the need for further research to understand its mechanisms.
- Klíčová slova
- First-episode schizophrenia, Longitudinal design, MRI, Negative symptoms, Ventricular volumes,
- MeSH
- dospělí MeSH
- lidé MeSH
- longitudinální studie MeSH
- magnetická rezonanční tomografie * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozkové komory diagnostické zobrazování patologie MeSH
- progrese nemoci MeSH
- schizofrenie * diagnostické zobrazování patologie patofyziologie MeSH
- studie případů a kontrol MeSH
- ventriculi laterales diagnostické zobrazování patologie 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
Maternal immune activation has been identified as a significant risk factor for schizophrenia. Using rodent models, past work has demonstrated various behavioral and brain impairments in offspring after immune-activating events. We applied 5 mg/kg of poly(I:C) on gestation day 9 to pregnant mouse dams, whose offspring were then stressed during puberty. We show impairments in attentional set-shifting in a T-maze, and a decreased number of parvalbumin-positive interneurons in the hippocampus as a result of peripubertal stress specifically in females.
- Klíčová slova
- Behavioral tests, Cognitive deficit, Immunochallenge, Interneurons, Maternal immune activation, Mouse, Poly(I:C), Prenatal infection, Schizophrenia,
- MeSH
- chování zvířat fyziologie MeSH
- exekutivní funkce fyziologie MeSH
- hipokampus cytologie MeSH
- infekční komplikace v těhotenství * chemicky indukované imunologie MeSH
- interneurony cytologie MeSH
- kognitivní dysfunkce etiologie patologie patofyziologie MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- poly I-C aplikace a dávkování MeSH
- pozornost fyziologie MeSH
- psychický stres komplikace patologie patofyziologie MeSH
- schizofrenie etiologie imunologie patologie patofyziologie MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice chemicky indukované patologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- poly I-C 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.
- Klíčová slova
- bipolar disorder, education, intelligence, neuroimaging, relatives, schizophrenia,
- 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
Recent MRI studies have shown that abnormal functional connections in schizophrenia coexist with subtle changes in the structure of axons in the brain. However, there is a discrepancy in the literature concerning the relationship between white matter abnormalities and the occurrence of negative psychopathological symptoms. In the present study, we investigate the relationship between the altered white matter structure and specific psychopathology symptoms, i.e., subscales of Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptoms Scale (BNSS) in a sample of schizophrenia outpatients. For investigation on white matter abnormalities in schizophrenia, the diffusion tensor imaging analysis of between-group differences in main diffusion parameters by tract-based spatial statistics was conducted on schizophrenia outpatients and healthy controls. Hence, the correlation of PANSS and BNSS psychopathology subscales in the clinical group with fractional anisotropy was analyzed in the 17 selected cortical regions of interest. Presented between-group results revealed widespread loss of white matter integrity located across the brain in schizophrenia outpatients. Results on the white matter relationship with psychopathology revealed the negative correlation between fractional anisotropy in the left orbital prefrontal cortex, right Heschl's gyrus, bilateral precuneus and posterior cingulate cortex and the severity of asociality, as assessed with the BNSS. In conclusion, the presented study confirms the previous evidence on the widespread white matter abnormalities in schizophrenia outpatients and indicates the existence of the subtle but specific association between fractional anisotropy in the fronto-temporo-parietal regions with the asociality. Recent MRI studies have shown that abnormal functional connections in schizophrenia coexist with subtle changes in the structure of axons in the brain. However, there is a discrepancy in the literature concerning the relationship between white matter abnormalities and the occurrence of negative psychopathological symptoms. In the present study, we investigate the relationship between the altered white matter structure and specific psychopathology symptoms, i.e., subscales of Positive and Negative Syndrome Scale (PANSS) and Brief Negative Symptoms Scale (BNSS) in a sample of schizophrenia outpatients. For investigation on white matter abnormalities in schizophrenia, the diffusion tensor imaging analysis of between-group differences in main diffusion parameters by tract-based spatial statistics was conducted on schizophrenia outpatients and healthy controls. Hence, the correlation of PANSS and BNSS psychopathology subscales in the clinical group with fractional anisotropy was analyzed in the 17 selected cortical regions of interest. Presented between-group results revealed widespread loss of white matter integrity located across the brain in schizophrenia outpatients. Results on the white matter relationship with psychopathology revealed the negative correlation between fractional anisotropy in the left orbital prefrontal cortex, right Heschl’s gyrus, bilateral precuneus and posterior cingulate cortex and the severity of asociality, as assessed with the BNSS. In conclusion, the presented study confirms the previous evidence on the widespread white matter abnormalities in schizophrenia outpatients and indicates the existence of the subtle but specific association between fractional anisotropy in the fronto-temporo-parietal regions with the asociality.
- MeSH
- bílá hmota patologie patofyziologie MeSH
- cingulární gyrus patologie patofyziologie MeSH
- dospělí MeSH
- lidé MeSH
- mapování mozku metody MeSH
- mozek abnormality patologie patofyziologie MeSH
- pacienti ambulantní MeSH
- prefrontální mozková kůra patofyziologie MeSH
- schizofrenie patologie patofyziologie MeSH
- zobrazování difuzních tenzorů metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Brain ventricles are among the most studied structures in psychotic illness. In our mini-review we present available evidence on brain ventricle changes during the course of schizophrenia, from high-risk subjects and the first episode of schizophrenia to patients with chronic schizophrenia. We present current findings on the relationship between ventricle changes and level of psychopathology. The potential pathophysiological background of ventricle changes is also discussed. Understanding the dynamics of brain ventricle changes could resolve long-standing questions on the proportion of neurodegenerative and neurodevelopmental processes in the pathophysiology of schizophrenia.
- Klíčová slova
- Brain ventricles, Neurodegeneration, Outcome, Psychosis, Schizophrenia,
- MeSH
- lidé MeSH
- mozkové komory patologie MeSH
- schizofrenie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
IMPORTANCE: Large-scale neuroimaging studies have revealed group differences in cortical thickness across many psychiatric disorders. The underlying neurobiology behind these differences is not well understood. OBJECTIVE: To determine neurobiologic correlates of group differences in cortical thickness between cases and controls in 6 disorders: attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD), obsessive-compulsive disorder (OCD), and schizophrenia. DESIGN, SETTING, AND PARTICIPANTS: Profiles of group differences in cortical thickness between cases and controls were generated using T1-weighted magnetic resonance images. Similarity between interregional profiles of cell-specific gene expression and those in the group differences in cortical thickness were investigated in each disorder. Next, principal component analysis was used to reveal a shared profile of group difference in thickness across the disorders. Analysis for gene coexpression, clustering, and enrichment for genes associated with these disorders were conducted. Data analysis was conducted between June and December 2019. The analysis included 145 cohorts across 6 psychiatric disorders drawn from the ENIGMA consortium. The numbers of cases and controls in each of the 6 disorders were as follows: ADHD: 1814 and 1602; ASD: 1748 and 1770; BD: 1547 and 3405; MDD: 2658 and 3572; OCD: 2266 and 2007; and schizophrenia: 2688 and 3244. MAIN OUTCOMES AND MEASURES: Interregional profiles of group difference in cortical thickness between cases and controls. RESULTS: A total of 12 721 cases and 15 600 controls, ranging from ages 2 to 89 years, were included in this study. Interregional profiles of group differences in cortical thickness for each of the 6 psychiatric disorders were associated with profiles of gene expression specific to pyramidal (CA1) cells, astrocytes (except for BD), and microglia (except for OCD); collectively, gene-expression profiles of the 3 cell types explain between 25% and 54% of variance in interregional profiles of group differences in cortical thickness. Principal component analysis revealed a shared profile of difference in cortical thickness across the 6 disorders (48% variance explained); interregional profile of this principal component 1 was associated with that of the pyramidal-cell gene expression (explaining 56% of interregional variation). Coexpression analyses of these genes revealed 2 clusters: (1) a prenatal cluster enriched with genes involved in neurodevelopmental (axon guidance) processes and (2) a postnatal cluster enriched with genes involved in synaptic activity and plasticity-related processes. These clusters were enriched with genes associated with all 6 psychiatric disorders. CONCLUSIONS AND RELEVANCE: In this study, shared neurobiologic processes were associated with differences in cortical thickness across multiple psychiatric disorders. These processes implicate a common role of prenatal development and postnatal functioning of the cerebral cortex in these disorders.
- MeSH
- analýza hlavních komponent MeSH
- bipolární porucha diagnostické zobrazování patologie MeSH
- depresivní porucha unipolární diagnostické zobrazování patologie MeSH
- dítě MeSH
- dospělí MeSH
- exprese genu fyziologie MeSH
- hyperkinetická porucha diagnostické zobrazování patologie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozková kůra cytologie diagnostické zobrazování růst a vývoj patologie MeSH
- obsedantně kompulzivní porucha diagnostické zobrazování patologie MeSH
- poruchy autistického spektra diagnostické zobrazování patologie MeSH
- předškolní dítě MeSH
- schizofrenie diagnostické zobrazování patologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- výpočetní biologie MeSH
- vývoj člověka fyziologie MeSH
- vývoj plodu fyziologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- arterioly diagnostické zobrazování patologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- retinální cévy diagnostické zobrazování patologie MeSH
- schizofrenie diagnostické zobrazování patologie MeSH
- senioři MeSH
- venuly diagnostické zobrazování patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- dopisy MeSH
OBJECTIVE: The cerebellum is involved in cognitive processing and emotion control. Cerebellar alterations could explain symptoms of schizophrenia spectrum disorder (SZ) and bipolar disorder (BD). In addition, literature suggests that lithium might influence cerebellar anatomy. Our aim was to study cerebellar anatomy in SZ and BD, and investigate the effect of lithium. METHODS: Participants from 7 centers worldwide underwent a 3T MRI. We included 182 patients with SZ, 144 patients with BD, and 322 controls. We automatically segmented the cerebellum using the CERES pipeline. All outputs were visually inspected. RESULTS: Patients with SZ showed a smaller global cerebellar gray matter volume compared to controls, with most of the changes located to the cognitive part of the cerebellum (Crus II and lobule VIIb). This decrease was present in the subgroup of patients with recent-onset SZ. We did not find any alterations in the cerebellum in patients with BD. However, patients medicated with lithium had a larger size of the anterior cerebellum, compared to patients not treated with lithium. CONCLUSION: Our multicenter study supports a distinct pattern of cerebellar alterations in SZ and BD.
- Klíčová slova
- cerebellum, lithium, parcellation, segmentation,
- MeSH
- antimanika škodlivé účinky MeSH
- bipolární porucha diagnostické zobrazování farmakoterapie patologie MeSH
- dospělí MeSH
- kůra mozečku diagnostické zobrazování účinky léků patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- mladý dospělý MeSH
- schizofrenie diagnostické zobrazování farmakoterapie patologie MeSH
- sloučeniny lithia škodlivé účinky 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
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- antimanika MeSH
- sloučeniny lithia 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.
- Klíčová slova
- Bipolar disorder, Familial risk, Imaging, Meta-analysis, Neurodevelopment, Schizophrenia,
- 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