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1.
Schizophr Bull ; 48(3): 563-574, 2022 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-35352811

RESUMO

BACKGROUND AND HYPOTHESIS: Machine learning approaches using structural magnetic resonance imaging (MRI) can be informative for disease classification; however, their applicability to earlier clinical stages of psychosis and other disease spectra is unknown. We evaluated whether a model differentiating patients with chronic schizophrenia (ChSZ) from healthy controls (HCs) could be applied to earlier clinical stages such as first-episode psychosis (FEP), ultra-high risk for psychosis (UHR), and autism spectrum disorders (ASDs). STUDY DESIGN: Total 359 T1-weighted MRI scans, including 154 individuals with schizophrenia spectrum (UHR, n = 37; FEP, n = 24; and ChSZ, n = 93), 64 with ASD, and 141 HCs, were obtained using three acquisition protocols. Of these, data regarding ChSZ (n = 75) and HC (n = 101) from two protocols were used to build a classifier (training dataset). The remainder was used to evaluate the classifier (test, independent confirmatory, and independent group datasets). Scanner and protocol effects were diminished using ComBat. STUDY RESULTS: The accuracy of the classifier for the test and independent confirmatory datasets were 75% and 76%, respectively. The bilateral pallidum and inferior frontal gyrus pars triangularis strongly contributed to classifying ChSZ. Schizophrenia spectrum individuals were more likely to be classified as ChSZ compared to ASD (classification rate to ChSZ: UHR, 41%; FEP, 54%; ChSZ, 70%; ASD, 19%; HC, 21%). CONCLUSION: We built a classifier from multiple protocol structural brain images applicable to independent samples from different clinical stages and spectra. The predictive information of the classifier could be useful for applying neuroimaging techniques to clinical differential diagnosis and predicting disease onset earlier.


Assuntos
Transtorno do Espectro Autista , Transtornos Psicóticos , Esquizofrenia , Transtorno do Espectro Autista/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
2.
Asian J Psychiatr ; 71: 103055, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35303593

RESUMO

BACKGROUND: Patients with schizophrenia consistently present pervasive cognitive deficits, but the neurobiological mechanism of cognitive impairments remains unclear. By analyzing regional homogeneity (ReHo) of resting-state functional Magnetic Resonance Imaging, this study aimed to explore the association between brain functional alterations and cognitive deficits in first-episode schizophrenia (FES) with a relatively large sample. METHODS: A total of 187 patients with FES and 100 healthy controls from 3 independent cohorts underwent resting-state functional magnetic resonance scans. The MATRICS Consensus Cognitive Battery (MCCB) was used to assess cognitive function. Partial correlation analysis was performed between abnormal ReHo values and the severity of symptoms and cognitive deficits. RESULTS: Compared with healthy controls, ReHo values increased in right superior frontal cortex and decreased in right anterior cingulate cortex (ACC), left middle occipital gyrus (MOG), left cuneus, right posterior cingulate cortex (PCC), and right superior occipital gyrus in schizophrenia patients. ReHo values in ACC, PCC and superior occipital gyrus were correlated with PANSS scores. In addition, ReHo values in ACC and MOG were negatively correlated with working memory; left cuneus was positively correlated with multiple cognitive domains (speed of processing, attention/vigilance and social cognition); PCC was positively correlated with verbal learning; right superior occipital gyrus was positively correlated with speed of processing and social cognition. CONCLUSION: In conclusion, we found widespread ReHo alterations and cognitive dysfunction in FES. And the pathophysiology mechanism of a wide range of cognitive deficits may be related to abnormal spontaneous brain activity.


Assuntos
Disfunção Cognitiva , Esquizofrenia , Encéfalo , Mapeamento Encefálico/métodos , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
3.
Med Image Anal ; 78: 102413, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35305447

RESUMO

Functional magnetic resonance imaging (fMRI) as a promising tool to investigate psychotic disorders can be decomposed into useful imaging features such as time courses (TCs) of independent components (ICs) and functional network connectivity (FNC) calculated by TC cross-correlation. TCs reflect the temporal dynamics of brain activity and the FNC characterizes temporal coherence across intrinsic brain networks. Both features have been used as input to deep learning approaches with decent results. However, few studies have tried to leverage their complementary information to learn optimal representations at multiple facets. Motivated by this, we proposed a Hybrid Deep Learning Framework integrating brain Connectivity and Activity (HDLFCA) together by combining convolutional recurrent neural network (C-RNN) and deep neural network (DNN), aiming to improve classification accuracy and interpretability simultaneously. Specifically, C-RNNAM was proposed to extract temporal dynamic dependencies with an attention module (AM) to automatically learn discriminative knowledge from TC nodes, while DNN was applied to identify the most group-discriminative FNC patterns with layer-wise relevance propagation (LRP). Then, both prediction outputs were concatenated to build a new feature matrix, generating the final decision by logistic regression. The effectiveness of HDLFCA was validated on both multi-site schizophrenia (SZ, n ∼ 1100) and public autism datasets (ABIDE, n ∼ 1522) by outperforming 12 alternative models at 2.8-8.9% accuracy, including 8 models using either static FNC or TCs and 4 models using dynamic FNC. Appreciable classification accuracy was achieved for HC vs. SZ (85.3%) and HC vs. Autism (72.4%) respectively. More importantly, the most group-discriminative brain regions can be easily attributed and visualized, providing meaningful biological interpretability and highlighting the great potential of the proposed HDLFCA model in the identification of valid neuroimaging biomarkers.


Assuntos
Encéfalo/fisiopatologia , Aprendizado Profundo , Imageamento por Ressonância Magnética , Redes Neurais de Computação , Esquizofrenia , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia
4.
Transl Psychiatry ; 12(1): 120, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338111

RESUMO

A puzzling feature of schizophrenia, is the long latency between the beginning of neuropathological changes and the clinical presentation that may be two decades later. Abnormalities in oligodendrocyte function may explain this latency, because mature oligodendrocytes produce myelination, and if myelination were abnormal from the outset, it would cause the synaptic dysfunction and abnormal neural tracts that are underpinning features of schizophrenia. The hypothesis is that latency is caused by events that occur in some patients as early as in-utero or infancy, because clones of abnormal, myelinating oligodendrocytes may arise at that time; their number doubles every ~2 years, so their geometric increase between birth and age twenty, when clinical presentation occurs, is about 1000-fold plus the effect of compounding. For those patients in particular, the long latency is because of a small but ongoing increase in volume of the resulting, abnormally myelinated neural tracts until, after a long latent interval, a critical mass is reached that allows the full clinical features of schizophrenia. During latency, there may be behavioral aberrancies because of abnormally myelinated neural tracts but they are insufficiently numerous for the clinical syndrome. The occurrence of behavioral symptoms during the long latent period, substantiates the hypothesis that abnormal oligodendrocytes explain the latency in some patients. Treatment with fingolimod or siponimod benefits both oligodendrocytes and neural tracts. Clinical trial would validate their potential benefit in appropriate patients with schizophrenia and, concurrently, would validate the hypothesis.


Assuntos
Esquizofrenia , Encéfalo/patologia , Células Cultivadas , Feminino , Humanos , Bainha de Mielina/patologia , Oligodendroglia/patologia , Gravidez , Esquizofrenia/patologia
5.
Asian J Psychiatr ; 70: 103042, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35219980

RESUMO

OBJECTIVE: Recent studies have examined retinal vascular abnormalities in schizophrenia as retinal vascular imaging is a non-invasive proxy to cerebral microvasculature. However, relation between retinal vascular abnormalities and brain structure is not well examined in schizophrenia. Hence in this study, for the first time, we examined the relationship between retinal vascular measures and brain white matter lesions in schizophrenia. We examined brain white matter lesions as they are considered a predictive marker for future adverse cerebrovascular event. METHODS: We acquired retinal vascular images of both eyes using a non-mydriatic camera and calculated retinal vascular diameter, tortuosity, trajectory and fractal dimension using validated methods. All patients underwent Magnetic Resonance Imaging of bran and we computed white matter hypo-intensities using Freesurfer software. We performed a linear regression analysis to examine the relationship between white matter hypo-intensities and retinal vascular measures controlling for age, sex, fasting blood sugar, creatinine, whole-brain volume, and antipsychotic dose. RESULTS: The regression model was significant in Schizophrenia patients (R=0.983;R2 =0.966;-F=10.849;p = 0.008) but not in healthy volunteers (R=0.828;R2 =0.686;F=0.182; p = 0.963). Among the retinal vascular measures, arterial tortuosity (ß = 0.963;p-0.002), tortuosity (ß = -1.002;p = 0.001) and fractal dimension (ß = -0.688;p = 0.014) were significant predictors of white matter lesions. DISCUSSION: The current study's findings support the conclusion that retinal vascular fractal dimension and tortuosity are associated with changes in cerebral white matter and may be considered proxy markers for cerebral microvasculature in schizophrenia. Considering the relationship between white matter lesions and stroke, these observations could have important clinical implications to screen schizophrenia patients for risk of adverse cerebrovascular event.


Assuntos
Esquizofrenia , Substância Branca , Encéfalo/patologia , Humanos , Imageamento por Ressonância Magnética , Vasos Retinianos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
6.
Sci Rep ; 12(1): 1870, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115592

RESUMO

Neurodevelopmental and neurodegenerative pathology occur in Schizophrenia. This study compared the utility of corneal confocal microscopy (CCM), an ophthalmic imaging technique with MRI brain volumetry in quantifying neuronal pathology and its relationship to cognitive dysfunction and symptom severity in schizophrenia. Thirty-six subjects with schizophrenia and 26 controls underwent assessment of cognitive function, symptom severity, CCM and MRI brain volumetry. Subjects with schizophrenia had lower cognitive function (P ≤ 0.01), corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), CNBD:CNFD ratio (P < 0.0001) and cingulate gyrus volume (P < 0.05) but comparable volume of whole brain (P = 0.61), cortical gray matter (P = 0.99), ventricle (P = 0.47), hippocampus (P = 0.10) and amygdala (P = 0.68). Corneal nerve measures and cingulate gyrus volume showed no association with symptom severity (P = 0.35-0.86 and P = 0.50) or cognitive function (P = 0.35-0.86 and P = 0.49). Corneal nerve measures were not associated with metabolic syndrome (P = 0.61-0.64) or diabetes (P = 0.057-0.54). The area under the ROC curve distinguishing subjects with schizophrenia from controls was 88% for CNFL, 84% for CNBD and CNBD:CNFD ratio, 79% for CNFD and 73% for the cingulate gyrus volume. This study has identified a reduction in corneal nerve fibers and cingulate gyrus volume in schizophrenia, but no association with symptom severity or cognitive dysfunction. Corneal nerve loss identified using CCM may act as a rapid non-invasive surrogate marker of neurodegeneration in patients with schizophrenia.


Assuntos
Encéfalo/diagnóstico por imagem , Córnea/inervação , Imageamento por Ressonância Magnética , Microscopia Confocal , Fibras Nervosas/patologia , Esquizofrenia/diagnóstico por imagem , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Cognição , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Índice de Gravidade de Doença , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-35063597

RESUMO

Schizophrenia is associated with disrupted integrity of white matter microstructure of a variety of brain regions, especially the corpus callosum (CC). Chronic subclinical inflammation is considered to be one of the factors involved in the pathogenesis of this disease, and increased levels of peripheral inflammatory markers are often observed in schizophrenia patients. Therefore, we decided to investigate whether the integrity of the corpus callosum is correlated with levels of these markers. A total of 50 patients with stable chronic schizophrenia (SCH) and 30 controls (CON) were enrolled in the study. All participants underwent psychiatric evaluation, neuroimaging, and blood sampling including the measurement of serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL - 10), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and C-reactive protein (CRP). Additional potentially related factors, such as age, gender, BMI, smoking, disease duration, and treatment were included in the analysis. Significantly higher IL-6 and IFN-γ levels were observed in SCH compared to CON. In SCH, IFN-γ was positively correlated with mean diffusivity of region 2 of the CC. In CON, IL-6 was inversely correlated with fractional anisotropy of region 1 of the CC. These results support the potential influence of peripheral inflammatory markers on the integrity of the CC in schizophrenia, but require verification in longitudinal studies.


Assuntos
Esquizofrenia , Substância Branca , Anisotropia , Corpo Caloso/diagnóstico por imagem , Humanos , Interleucina-6 , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
8.
PLoS One ; 17(1): e0262717, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35073334

RESUMO

High resolution in situ hybridization (ISH) images of the brain capture spatial gene expression at cellular resolution. These spatial profiles are key to understanding brain organization at the molecular level. Previously, manual qualitative scoring and informatics pipelines have been applied to ISH images to determine expression intensity and pattern. To better capture the complex patterns of gene expression in the human cerebral cortex, we applied a machine learning approach. We propose gene re-identification as a contrastive learning task to compute representations of ISH images. We train our model on an ISH dataset of ~1,000 genes obtained from postmortem samples from 42 individuals. This model reaches a gene re-identification rate of 38.3%, a 13x improvement over random chance. We find that the learned embeddings predict expression intensity and pattern. To test generalization, we generated embeddings in a second dataset that assayed the expression of 78 genes in 53 individuals. In this set of images, 60.2% of genes are re-identified, suggesting the model is robust. Importantly, this dataset assayed expression in individuals diagnosed with schizophrenia. Gene and donor-specific embeddings from the model predict schizophrenia diagnosis at levels similar to that reached with demographic information. Mutations in the most discriminative gene, Sodium Voltage-Gated Channel Beta Subunit 4 (SCN4B), may help understand cardiovascular associations with schizophrenia and its treatment. We have publicly released our source code, embeddings, and models to spur further application to spatial transcriptomics. In summary, we propose and evaluate gene re-identification as a machine learning task to represent ISH gene expression images.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Hibridização In Situ/métodos , Redes Neurais de Computação , Transcriptoma , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Estudos de Casos e Controles , Conjuntos de Dados como Assunto , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/metabolismo , Esquizofrenia/patologia , Adulto Jovem
9.
Schizophr Res ; 240: 125-131, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34999371

RESUMO

BACKGROUND: Hippocampal volume changes have been reported in schizophrenia patients and their relatives and are proposed to contribute to the pathophysiology of schizophrenia. However, volume changes in the total hippocampus have not been consistently reported in relatives. The hippocampus consists of multiple subregions, and based on previous inconsistent results, subtle changes in specific subregions may occur in relatives. Here, we examined the subregion volumes in unaffected, high-functioning relatives (URs) without any psychiatric symptoms with high genetic loading with at least one first-degree relative diagnosed with schizophrenia and at least one or more other affected first- to third-degree relatives. METHODS: We acquired structural magnetic resonance imaging data from 50 URs, 101 first-episode psychosis (FEP) patients, and 101 healthy controls (HCs). The cornu ammonis (CA), dentate gyrus, and subiculum subfields were automatically segmented using FreeSurfer 7.1.0. Each subregion volume was compared across the groups. RESULTS: Compared with the HCs, the URs had a significant volume reduction in the left anterior CA (p = 0.039, Cohen's d = 0.480). In addition, the URs had a significantly larger right posterior subiculum (p = 0.001, Cohen's d = 0.541) than the FEP. CONCLUSIONS: The smaller left anterior CA in the URs may reflect their genetic vulnerability to schizophrenia and supports previous findings suggesting specific vulnerability in this region. The volume differences between the URs and FEP patients in the right posterior subiculum may suggest that a smaller volume in this region may reflect a risk for schizophrenia other than genetic vulnerability.


Assuntos
Transtornos Psicóticos , Esquizofrenia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Tamanho do Órgão , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/genética , Transtornos Psicóticos/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/genética , Esquizofrenia/patologia
10.
Neurosci Biobehav Rev ; 132: 1205-1213, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34718049

RESUMO

Although schizophrenia is associated with increased presynaptic dopamine function in the striatum, it remains unclear if neuromelanin levels, which are thought to serve as a biomarker for midbrain dopamine neuron function, are increased in patients with schizophrenia. We conducted a systematic review and meta-analysis of magnetic resonance imaging (MRI) and postmortem studies comparing neuromelanin (NM) levels between patients with schizophrenia and healthy controls (HCs). Standard mean differences were calculated to assess group differences in NM accumulation levels between patients with schizophrenia and HCs. This study included 7 articles in total. Five studies employed NM-sensitive MRI (NM-MRI) and two were postmortem brain studies. The patient group (n = 163) showed higher NM levels in the substantia nigra (SN) than HCs (n = 228) in both the analysis of the seven studies and the subgroup analysis of the 5 NM-MRI studies. This analysis suggest increased NM levels in the SN may be a potential biomarker for stratifying schizophrenia, warranting further research that accounts for the heterogeneity of this disorder.


Assuntos
Esquizofrenia , Humanos , Imageamento por Ressonância Magnética/métodos , Melaninas , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Substância Negra/diagnóstico por imagem , Substância Negra/patologia
11.
Schizophr Bull ; 48(1): 241-250, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34508358

RESUMO

Schizophrenia is a complex and heterogeneous syndrome. Whether quantitative imaging biomarkers can identify discrete subgroups of patients as might be used to foster personalized medicine approaches for patient care remains unclear. Cross-sectional structural MR images of 163 never-treated first-episode schizophrenia patients (FES) and 133 chronically ill patients with midcourse schizophrenia from the Bipolar and Schizophrenia Network for Intermediate Phenotypes (B-SNIP) consortium and a total of 403 healthy controls were recruited. Morphometric measures (cortical thickness, surface area, and subcortical structures) were extracted for each subject and then the optimized subtyping results were obtained with nonsupervised cluster analysis. Three subgroups of patients defined by distinct patterns of regional cortical and subcortical morphometric features were identified in FES. A similar three subgroup pattern was identified in the independent dataset of patients from the multi-site B-SNIP consortium. Similarities of classification patterns across these two patient cohorts suggest that the 3-group typology is relatively stable over the course of illness. Cognitive functions were worse in subgroup 1 with midcourse schizophrenia than those in subgroup 3. These findings provide novel insight into distinct subgroups of patients with schizophrenia based on structural brain features. Findings of different cognitive functions among the subgroups support clinical differences in the MRI-defined illness subtypes. Regardless of clinical presentation and stage of illness, anatomic MR subgrouping biomarkers can separate neurobiologically distinct subgroups of schizophrenia patients, which represent an important and meaningful step forward in differentiating subtypes of patients for studies of illness neurobiology and potentially for clinical trials.


Assuntos
Encéfalo/patologia , Esquizofrenia/classificação , Esquizofrenia/patologia , Adulto , Encéfalo/diagnóstico por imagem , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia
12.
Hum Brain Mapp ; 43(1): 352-372, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34498337

RESUMO

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.


Assuntos
Tonsila do Cerebelo/patologia , Corpo Estriado/patologia , Hipocampo/patologia , Neuroimagem , Esquizofrenia/patologia , Tálamo/patologia , Tonsila do Cerebelo/diagnóstico por imagem , Corpo Estriado/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Humanos , Estudos Multicêntricos como Assunto , Esquizofrenia/diagnóstico por imagem , Tálamo/diagnóstico por imagem
13.
Schizophr Bull ; 48(1): 80-89, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34554256

RESUMO

BACKGROUND: Retinovascular changes are reported on fundus imaging in schizophrenia (SZ). This is the first study to use swept-source optical coherence tomography angiography (OCT-A) to comprehensively examine retinal microvascular changes in SZ. METHODS: This study included 30 patients with SZ/schizoaffective disorder (8 early and 15 chronic) and 22 healthy controls (HCs). All assessments were performed at Beth Israel Deaconess Medical Center and Massachusetts Eye and Ear. All participants underwent swept-source OCT-A of right (oculus dextrus [OD]) and left (oculus sinister [OS]) eye, clinical, and cognitive assessments. Macular OCT-A images (6 × 6 mm) were collected with the DRI Topcon Triton for superficial, deep, and choriocapillaris vascular regions. Microvasculature was quantified using vessel density (VD), skeletonized vessel density (SVD), fractal dimension (FD), and vessel diameter index (VDI). RESULTS: Twenty-one HCs and 26 SZ subjects were included. Compared to HCs, SZ patients demonstrated higher overall OD superficial SVD, OD choriocapillaris VD, and OD choriocapillaris SVD, which were primarily observed in the central, central and outer superior, and central and outer inferior/superior, respectively. Early-course SZ subjects had significantly higher OD superficial VD, OD choriocapillaris SVD, and OD choriocapillaris FD compared to matched HCs. Higher bilateral (OU) superficial VD correlated with lower Positive and Negative Syndrome Scale (PANSS) positive scores, and higher OU deep VDI was associated with higher PANSS negative scores. CONCLUSIONS AND RELEVANCE: These results suggest the presence of microvascular dysfunction associated with early-stage SZ. Clinical associations with microvascular alterations further implicate this hypothesis, with higher measures being associated with worse symptom severity and functioning in early stages and with lower symptom severity and better functioning in later stages.


Assuntos
Microvasos/patologia , Transtornos Psicóticos/patologia , Vasos Retinianos/patologia , Esquizofrenia/patologia , Tomografia de Coerência Óptica , Adulto , Angiografia , Feminino , Humanos , Masculino , Microvasos/diagnóstico por imagem , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/fisiopatologia , Adulto Jovem
14.
Behav Brain Res ; 419: 113678, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-34838932

RESUMO

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.


Assuntos
Atenção/fisiologia , Disfunção Cognitiva/fisiopatologia , Função Executiva/fisiologia , Complicações Infecciosas na Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Esquizofrenia/fisiopatologia , Estresse Psicológico/fisiopatologia , Animais , Comportamento Animal/fisiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/patologia , Modelos Animais de Doenças , Feminino , Hipocampo/citologia , Interneurônios/citologia , Masculino , Camundongos Endogâmicos C57BL , Poli I-C/administração & dosagem , Gravidez , Complicações Infecciosas na Gravidez/induzido quimicamente , Complicações Infecciosas na Gravidez/imunologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , Esquizofrenia/etiologia , Esquizofrenia/imunologia , Esquizofrenia/patologia , Estresse Psicológico/complicações , Estresse Psicológico/patologia
15.
Hum Brain Mapp ; 43(1): 566-575, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32463560

RESUMO

Patients with schizophrenia have patterns of brain deficits including reduced cortical thickness, subcortical gray matter volumes, and cerebral white matter integrity. We proposed the regional vulnerability index (RVI) to translate the results of Enhancing Neuro Imaging Genetics Meta-Analysis studies to the individual level. We calculated RVIs for cortical, subcortical, and white matter measurements and a multimodality RVI. We evaluated RVI as a measure sensitive to schizophrenia-specific neuroanatomical deficits and symptoms and studied the timeline of deficit formations in: early (≤5 years since diagnosis, N = 45, age = 28.8 ± 8.5); intermediate (6-20 years, N = 30, age 43.3 ± 8.6); and chronic (21+ years, N = 44, age = 52.5 ± 5.2) patients and healthy controls (N = 76, age = 38.6 ± 12.4). All RVIs were significantly elevated in patients compared to controls, with the multimodal RVI showing the largest effect size, followed by cortical, white matter and subcortical RVIs (d = 1.57, 1.23, 1.09, and 0.61, all p < 10-6 ). Multimodal RVI was significantly correlated with multiple cognitive variables including measures of visual learning, working memory and the total score of the MATRICS consensus cognitive battery, and with negative symptoms. The multimodality and white matter RVIs were significantly elevated in the intermediate and chronic versus early diagnosis group, consistent with ongoing progression. Cortical RVI was stable in the three disease-duration groups, suggesting neurodevelopmental origins of cortical deficits. In summary, neuroanatomical deficits in schizophrenia affect the entire brain; the heterochronicity of their appearance indicates both the neurodevelopmental and progressive nature of this illness. These deficit patterns may be useful for early diagnosis and as quantitative targets for more effective treatment strategies aiming to alter these neuroanatomical deficit patterns.


Assuntos
Córtex Cerebral/patologia , Disfunção Cognitiva/fisiopatologia , Progressão da Doença , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Substância Branca/patologia , Adolescente , Adulto , Idoso , Córtex Cerebral/diagnóstico por imagem , Doença Crônica , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Imagem de Tensor de Difusão , Substância Cinzenta/diagnóstico por imagem , Humanos , Pessoa de Meia-Idade , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto Jovem
16.
Hum Brain Mapp ; 43(1): 399-413, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-32643841

RESUMO

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.


Assuntos
Transtorno Bipolar/patologia , Encéfalo/patologia , Transtorno Depressivo Maior/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Esquizofrenia/patologia , Transtornos Relacionados ao Uso de Substâncias/patologia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Humanos , Esquizofrenia/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem
17.
Schizophr Bull ; 48(1): 231-240, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34313782

RESUMO

Cortical thickness reductions are evident in schizophrenia (SZ). Associations between antipsychotic medications (APMs) and cortical morphometry have been explored in SZ patients. This raises the question of whether the reconfiguration of morphological architecture by APM plays potential compensatory roles for abnormalities in the cerebral cortex. Structural magnetic resonance imaging was obtained from 127 medication-naive first-episode SZ patients and 133 matched healthy controls. Patients received 12 weeks of APM and were categorized as responders (n = 75) or nonresponders (NRs, n = 52) at follow-up. Using surface-based morphometry and structural covariance (SC) analysis, this study investigated the short-term effects of antipsychotics on cortical thickness and cortico-cortical covariance. Global efficiency was computed to characterize network integration of the large-scale structural connectome. The relationship between covariance and cortical thinning was examined by SC analysis among the top-n regions with thickness reduction. Widespread cortical thickness reductions were observed in pre-APM patients. Post-APM patients showed more reductions in cortical thickness, even in the frontotemporal regions without baseline reductions. Covariance analysis revealed strong cortico-cortical covariance and higher network integration in responders than in NRs. For the NRs, some of the prefrontal and temporal nodes were not covariant between the top-n regions with cortical thickness reduction. Antipsychotic effects are not restricted to a single brain region but rather exhibit a network-level covariance pattern. Neuroimaging connectomics highlights the positive effects of antipsychotics on the reconfiguration of brain architecture, suggesting that abnormalities in regional morphology may be compensated by increasing interregional covariance when symptoms are controlled by antipsychotics.


Assuntos
Antipsicóticos/farmacologia , Córtex Cerebral , Rede Nervosa , Esquizofrenia , Adulto , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/patologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/patologia
18.
Schizophr Bull ; 48(1): 220-230, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34355246

RESUMO

Neurological soft signs (NSS) are related to grey matter and functional brain abnormalities in schizophrenia. Studies in healthy subjects suggest, that NSS are also linked to white matter. However, the association between NSS and white matter abnormalities in schizophrenia remains to be elucidated. The present study investigated, if NSS are related to white matter alterations in patients with schizophrenia. The total sample included 42 healthy controls and 41 patients with schizophrenia. We used the Neurological Evaluation Scale (NES), and we acquired diffusion weighted magnetic resonance imaging to assess white matter on a voxel-wise between subject statistic. In patients with schizophrenia, linear associations between NES with fractional anisotropy (FA), radial, axial, and mean diffusivity were analyzed with tract-based spatial statistics while controlling for age, medication dose, the severity of the disease, and motion. The main pattern of results in patients showed a positive association of NES with all diffusion measures except FA in important motor pathways: the corticospinal tract, internal capsule, superior longitudinal fascicle, thalamocortical radiations and corpus callosum. In addition, exploratory tractography analysis revealed an association of the right aslant with NES in patients. These results suggest that specific white matter alterations, that is, increased diffusivity might contribute to NSS in patients with schizophrenia.


Assuntos
Doenças do Sistema Nervoso/fisiopatologia , Transtornos Psicóticos/patologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Substância Branca/patologia , Adulto , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Humanos , Cápsula Interna/diagnóstico por imagem , Cápsula Interna/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Transtornos Psicóticos/complicações , Transtornos Psicóticos/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Esquizofrenia/complicações , Esquizofrenia/diagnóstico por imagem
19.
Schizophr Bull ; 48(1): 69-79, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34374427

RESUMO

Schizophrenia (SZ) and bipolar disorder (BD) share some similarities in terms of genetic-risk genes and abnormalities of gray-matter structure in the brain, but white matter (WM) abnormalities have not been studied in depth. We undertook a comparative multimodal meta-analysis to identify common and disorder-specific abnormalities in WM structure between SZ and BD. Anisotropic effect size-signed differential mapping software was used to conduct a comparative meta-analysis of 68 diffusion tensor imaging (DTI) and 34 voxel-based morphometry (VBM) studies comparing fractional anisotropy (FA) and white matter volume (WMV), respectively, between patients with SZ (DTI: N = 1543; VBM: N = 1068) and BD (DTI: N = 983; VBM: N = 518) and healthy controls (HCs). The bilateral corpus callosum (extending to the anterior and superior corona radiata) showed shared decreased WMV and FA in SZ and BD. Compared with BD patients, SZ patients showed remarkable disorder-specific WM abnormalities: decreased FA and increased WMV in the left cingulum, and increased FA plus decreased WMV in the right anterior limb of the internal capsule. SZ patients showed more extensive alterations in WM than BD cases, which may be the pathophysiological basis for the clinical continuity of both disorders. The disorder-specific regions in the left cingulum and right anterior limb of the internal capsule provided novel insights into both disorders. Our study adds value to further understanding of the pathophysiology, classification, and differential diagnosis of SZ and BD.


Assuntos
Transtorno Bipolar/patologia , Esquizofrenia/patologia , Substância Branca/patologia , Adulto , Transtorno Bipolar/diagnóstico por imagem , Imagem de Tensor de Difusão , Feminino , Humanos , Masculino , Esquizofrenia/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
20.
Hum Brain Mapp ; 43(1): 373-384, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017498

RESUMO

Early-onset psychosis disorders are serious mental disorders arising before the age of 18 years. Here, we investigate the largest neuroimaging dataset, to date, of patients with early-onset psychosis and healthy controls for differences in intracranial and subcortical brain volumes. The sample included 263 patients with early-onset psychosis (mean age: 16.4 ± 1.4 years, mean illness duration: 1.5 ± 1.4 years, 39.2% female) and 359 healthy controls (mean age: 15.9 ± 1.7 years, 45.4% female) with magnetic resonance imaging data, pooled from 11 clinical cohorts. Patients were diagnosed with early-onset schizophrenia (n = 183), affective psychosis (n = 39), or other psychotic disorders (n = 41). We used linear mixed-effects models to investigate differences in intracranial and subcortical volumes across the patient sample, diagnostic subgroup and antipsychotic medication, relative to controls. We observed significantly lower intracranial (Cohen's d = -0.39) and hippocampal (d = -0.25) volumes, and higher caudate (d = 0.25) and pallidum (d = 0.24) volumes in patients relative to controls. Intracranial volume was lower in both early-onset schizophrenia (d = -0.34) and affective psychosis (d = -0.42), and early-onset schizophrenia showed lower hippocampal (d = -0.24) and higher pallidum (d = 0.29) volumes. Patients who were currently treated with antipsychotic medication (n = 193) had significantly lower intracranial volume (d = -0.42). The findings demonstrate a similar pattern of brain alterations in early-onset psychosis as previously reported in adult psychosis, but with notably low intracranial volume. The low intracranial volume suggests disrupted neurodevelopment in adolescent early-onset psychosis.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Transtornos Psicóticos Afetivos/patologia , Encéfalo/patologia , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Adolescente , Transtornos Psicóticos Afetivos/diagnóstico por imagem , Idade de Início , Encéfalo/diagnóstico por imagem , Globo Pálido/diagnóstico por imagem , Globo Pálido/patologia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem
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