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1.
Sci Rep ; 10(1): 21803, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311571

RESUMO

Cortical thinning occurs throughout the entire life and extends to late-life neurodegeneration, yet the neurobiological substrates are poorly understood. Here, we used a virtual-histology technique and gene expression data from the Allen Human Brain Atlas to compare the regional profiles of longitudinal cortical thinning through life (4004 magnetic resonance images [MRIs]) with those of gene expression for several neuronal and non-neuronal cell types. The results were replicated in three independent datasets. We found that inter-regional profiles of cortical thinning related to expression profiles for marker genes of CA1 pyramidal cells, astrocytes and, microglia during development and in aging. During the two stages of life, the relationships went in opposite directions: greater gene expression related to less thinning in development and vice versa in aging. The association between cortical thinning and cell-specific gene expression was also present in mild cognitive impairment and Alzheimer's Disease. These findings suggest a role of astrocytes and microglia in promoting and supporting neuronal growth and dendritic structures through life that affects cortical thickness during development, aging, and neurodegeneration. Overall, the findings contribute to our understanding of the neurobiology underlying variations in MRI-derived estimates of cortical thinning through life and late-life disease.

2.
CNS Spectr ; : 1-5, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32772934

RESUMO

BACKGROUND.: Resistance to antipsychotic treatment affects up to 30% of patients with schizophrenia. Although the time course of development of treatment-resistant schizophrenia (TRS) varies from patient to patient, the reasons for these variations remain unknown. Growing evidence suggests brain dysconnectivity as a significant feature of schizophrenia. In this study, we compared fractional anisotropy (FA) of brain white matter between TRS and non-treatment-resistant schizophrenia (non-TRS) patients. Our central hypothesis was that TRS is associated with reduced FA values. METHODS.: TRS was defined as the persistence of moderate to severe symptoms after adequate treatment with at least two antipsychotics from different classes. Diffusion-tensor brain MRI obtained images from 34 TRS participants and 51 non-TRS. Whole-brain analysis of FA and axial, radial, and mean diffusivity were performed using Tract-Based Spatial Statistics (TBSS) and FMRIB's Software Library (FSL), yielding a contrast between TRS and non-TRS patients, corrected for multiple comparisons using family-wise error (FWE) < 0.05. RESULTS.: We found a significant reduction in FA in the splenium of corpus callosum (CC) in TRS when compared to non-TRS. The antipsychotic dose did not relate to the splenium CC. CONCLUSION.: Our results suggest that the focal abnormality of CC may be a potential biomarker of TRS.

3.
Hum Brain Mapp ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32596977

RESUMO

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega-analyses.

4.
JAMA Psychiatry ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32584945

RESUMO

Importance: Many psychiatric disorders can be conceptualized as disorders of brain maturation during childhood and adolescence. Discovering the neurobiological underpinnings of brain maturation may elucidate molecular pathways of vulnerability and resilience to such disorders. Objective: To investigate the underlying neurobiological mechanisms of age-associated cortical thinning during maturation and their implications for psychiatric disorders. Design, Setting, and Participants: This multicohort analysis used data from 3 community-based studies. The Saguenay Youth Study provided data from 1024 adolescents who were recruited at a single site in Quebec, Canada. The IMAGEN cohort provided data from 1823 participants who were recruited in 8 European cities. The Brazil High Risk Cohort Study for the Development of Childhood Psychiatric Disorders provided data from 815 participants who were recruited in 2 Brazilian cities. Cortical thickness was estimated from the results of magnetic resonance imaging (MRI) scans, and age-associated cortical thinning was estimated in 34 cortical regions. Gene expression from the Allen Human Brain Atlas was aligned with the same regions. Similarities in the interregional profiles of gene expression and the profiles of age-associated cortical thinning were measured. The involvement of dendrites, dendritic spines, and myelin was tested using 3 gene panels. Enrichment for genes associated with psychiatric disorders was tested among the genes associated with thinning and their coexpression networks. Data analysis was conducted between March and October 2019. Main Outcomes and Measures: MRI-derived estimates of age-associated cortical thinning and gene expression in 34 cortical regions. Results: A total of 3596 individuals aged 9 to 21 years were included in this study. Of those, 1803 participants (50.1%) were female, and the mean (SD) age was 15.2 (2.6) years. Interregional profiles of age-associated cortical thinning were associated with interregional gradients in the expression of genes associated with dendrites, dendritic spines, and myelin; the variance in thinning explained by the gene panels across different points ranged from 0.45% to 10.55% for the dendrite panel, 0.00% to 9.98% for the spine panel, and 0.19% to 26.39% for the myelin panel. These genes and their coexpression networks were enriched for genes associated with several psychiatric disorders. Conclusions and Relevance: In this study, genetic similarity between interregional variation in cortical thinning during maturation and multiple psychiatric disorders suggests overlapping molecular underpinnings. This finding adds to the understanding of the neurodevelopmental mechanisms of psychiatric disorders.

5.
CNS Spectr ; : 1-7, 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31845634

RESUMO

OBJECTIVE.: Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence. METHODS.: Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder. RESULTS.: Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers. CONCLUSIONS.: No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

6.
Epilepsy Res ; 147: 51-57, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30248630

RESUMO

PURPOSE: To evaluate if the duration of epilepsy influences MRI volumes of the hippocampus, amygdala, parahippocampal gyrus, entorhinal cortex and temporal pole of both hemispheres and epileptogenic hippocampus neuronal cell density and dentate gyrus granular cells distribution in patients with refractory mesial temporal lobe epilepsy due to hippocampal sclerosis (MTLE/HS). METHODS: Seventy-seven patients with refractory MTLE/HS submitted to surgery were included. Histopathological analysis included: (1) quantitative: hippocampal subfields and total estimated hippocampal cell density (HCD), thickness of the dentate gyrus - normal, thinning or dispersion; (2) qualitative: type of HS and granule cells pathology in the dentate gyrus (normal, neuronal cell loss, dispersion and bilamination). Automated MRI-derived measurements from bilateral temporal structures (hippocampus, amygdala, parahippocampal gyrus, temporal pole, entorhinal cortex) were obtained for 58 subjects. Histopathological and imaging findings were compared with data from specimens obtained in autopsies of age-matched individuals and living controls, respectively, and the data were adjusted for the age at epilepsy onset and the frequency of focal impaired awareness seizures/month. RESULTS: Forty-two (54.5%) patients presented right HS. The greater the duration of epilepsy, the smaller the total estimated HCD (p = 0.025; r = -0.259). Patients with a normal distribution of the granular cells had a shorter epilepsy duration than those with dispersion (p = 0.018) or thinning (p = 0.031). A reduced ipsilateral hippocampal volume (r = -0.551, p = 0.017) and a smaller hippocampal asymmetry index (r = -0.414, p = 0.002) were correlated to a longer epilepsy duration. The estimated HCD was correlated to the volume of the ipsilateral hippocampus (r = 0.420, p = 0.001). CONCLUSION: Our study showed an increasing atrophy of the ipsilateral hippocampus in patients with a longer epilepsy duration. Our data suggest that this reduction in hippocampal volume is related to neuronal loss. Besides that, we also showed an increased probability of exhibiting an abnormal distribution of the granular cells in the dentate gyrus in patients with longer epilepsy duration.


Assuntos
Mapeamento Encefálico , Encéfalo/patologia , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/metabolismo , Adolescente , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Contagem de Células , Epilepsia do Lobo Temporal/complicações , Feminino , Hipocampo/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurônios/patologia , Fosfopiruvato Hidratase/metabolismo , Esclerose/diagnóstico por imagem , Esclerose/patologia , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-29963652

RESUMO

Introduction: Using proton magnetic resonance spectroscopy imaging (1H-MRSI), the effects of early life stress (ELS) on nonhuman primate striatal neuronal integrity were examined as reflected by N-acetyl aspartate (NAA) concentrations. NAA measures were interrogated through examining their relationship to previously documented ELS markers -- cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) concentrations, hippocampal volume, body mass and behavioral timidity. Rodent models of depression exhibit increases in neurotrophic effects in the nucleus accumbens (NAcc). We hypothesized that rearing under conditions of ELS [Variable Foraging Demand: (VFD)] would produce persistent elevations of NAA concentrations (in absolute or ratio form) in ventral striatum/caudate nucleus (VS/CN) with altered correlation to ELS markers. Methods: Eleven bonnet macaque males reared under VFD conditions and seven age-matched control subjects underwent 1H-MRSI during young adulthood. Voxels were placed over ventral striatum/caudate nucleus (VS/CN) to capture NAcc. Cisternal CSF CRF concentrations, hippocampal volume, body mass and response to a human intruder had been previously determined. Results: VFD-reared monkeys exhibited significantly increased NAA/Cr concentrations in right VS/CN in comparison to normally-reared controls, controlling for multiple comparisons. In comparison to controls, VFD CSF CRF concentrations were directly associated with right VS/CN absolute NAA. Left hippocampal volume was inversely associated with left VS/CN N-acetyl aspartate/creatine (NAA/Cr) in VFD-reared but not in controls. Disruption of a normative inverse correlation between left VS/CN NAA and body mass was noted in VFD. Only non-VFD subjects exhibited a direct relationship between timidity response to an intruder and right VS/CN NAA. Conclusion: ELS produced persistent increases in VS/CN NAA, which demonstrated specific patterns of association (or lack thereof) to ELS markers in comparison to non-VFD subjects. The data are broadly consistent with a stable nonhuman primate phenotype of anxiety and mood disorder vulnerability whereby in vivo indicators of neuronal integrity, although reduced in hippocampus, are increased in striatum. The findings may provide a catalyst for further studies in humans and other species regarding a reciprocal hippocampal/NAcc relationship in affective disorders.

8.
Psychiatry Res Neuroimaging ; 275: 14-20, 2018 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-29548527

RESUMO

In this study, we employed the Maximum Uncertainty Linear Discriminant Analysis (MLDA) to investigate whether the structural brain patterns in first episode psychosis (FEP) patients would be more similar to patients with chronic schizophrenia (SCZ) or healthy controls (HC), from a schizophrenia model perspective. Brain regions volumetric data were estimated by using MRI images of SCZ and FEP patients and HC. First, we evaluated the MLDA performance in discriminating SCZ from controls, which provided a score based on a model for changes in brain structure in SCZ. In the following, we compared the volumetric patterns of FEP patients with patterns of SCZ and healthy controls using these scores. The FEP group had a score distribution more similar to patients with schizophrenia (p-value = .461; Cohen's d=-.15) in comparison with healthy subjects (p-value=.003; Cohen's d = .62). Structures related to the limbic system and the circuitry involved in goal-directed behaviours were the most discriminant regions. There is a distinct pattern of volumetric changes in patients with schizophrenia in contrast to healthy controls, and this pattern seem to be detectable already in FEP.


Assuntos
Encéfalo/patologia , Aprendizado de Máquina , Imagem por Ressonância Magnética/métodos , Neuroimagem/métodos , Reconhecimento Automatizado de Padrão/métodos , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico por imagem , Esquizofrenia/diagnóstico por imagem , Adulto Jovem
9.
J Psychiatr Res ; 96: 224-230, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29102817

RESUMO

BACKGROUND: The present study was designed to explore alterations in brain dynamics at rest that are associated with Obsessive Compulsive Symptoms (OCS) in childhood by measuring low frequency fluctuation of spontaneous brain activity in a large school community sample from a developing country. METHOD: Resting state functional magnetic resonance imaging data were collected in a sample of 655 children and adolescents (6-15 years old) from the brazilian 'High Risk Cohort Study for Psychiatric Disorders (HRC)'. OCS were assessed using items from the Compulsion and Obsessions section of the Development and Well-Being Assessment (DAWBA). The correlation between the fractional amplitude of low frequency fluctuations (fALFF) and the number of OCS were explored by using a general linear model, considering fALFF as response variable, OCS score as regressor and age, gender and site as nuisance variables. RESULTS: The number of OCS was positively correlated with the fALFF coefficients at the right sensorimotor cortex (pre-motor, primary motor cortex and post-central gyrus) and negatively correlated with the fALFF coefficients at the insula/superior temporal gyrus of both hemispheres. Our results were specific to OCS and not due to associations with overall psychopathology. CONCLUSIONS: Our results suggest that brain spontaneous activity at rest in the sensorimotor and insular/superior-temporal cortices may be involved in OCS in children. These findings need independent replication and future studies should determine whether brain spontaneous activity changes within these regions might be predictors of risk for obsessive-compulsive disorder latter in life.


Assuntos
Encéfalo/fisiopatologia , Transtorno Obsessivo-Compulsivo/fisiopatologia , Adolescente , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criança , Estudos de Coortes , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Transtorno Obsessivo-Compulsivo/diagnóstico por imagem , Escalas de Graduação Psiquiátrica , Descanso
11.
Front Neurosci ; 11: 18, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28174518

RESUMO

Given the relationship between language acquisition and music processing, musical perception (MP) skills have been proposed as a tool for early diagnosis of speech and language difficulties; therefore, a psychometric instrument is needed to assess music perception in children under 10 years of age, a crucial period in neurodevelopment. We created a set of 80 musical stimuli encompassing seven domains of music perception to inform perception of tonal, atonal, and modal stimuli, in a random sample of 1006 children, 6-13 years of age, equally distributed from first to fifth grades, from 14 schools (38% private schools) in So Paulo State. The underlying model was tested using confirmatory factor analysis. A model encompassing seven orthogonal specific domains (contour, loudness, scale, timbre, duration, pitch, and meter) and one general music perception factor, the "m-factor," showed excellent fit indices. The m-factor, previously hypothesized in the literature but never formally tested, explains 93% of the reliable variance in measurement, while only 3.9% of the reliable variance could be attributed to the multidimensionality caused by the specific domains. The 80 items showed no differential item functioning based on sex, age, or enrolment in public vs. private school, demonstrating the important psychometric feature of invariance. Like Charles Spearman's g-factor of intelligence, the m-factor is robust and reliable. It provides a convenient measure of auditory stimulus apprehension that does not rely on verbal information, offering a new opportunity to probe biological and psychological relationships with music perception phenomena and the etiologies of speech and language disorders.

12.
Psychiatry Clin Neurosci ; 71(3): 154-169, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27778421

RESUMO

Several studies have recently demonstrated that the volumes of specific brain regions are reduced in children and adolescents with post-traumatic stress disorder (PTSD) compared with those of healthy controls. Our study investigated the potential association between early traumatic experiences and altered brain regions and functions. We conducted a systematic review of the scientific literature regarding functional magnetic resonance imaging and a meta-analysis of structural magnetic resonance imaging studies that investigated cerebral region volumes in pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial volumes that fit the inclusion criteria were extracted and combined in a meta-analysis that assessed differences between groups. The meta-analysis found reduced total corpus callosum areas and reduced total cerebral and intracranial volumes in the patients with PTSD. The total hippocampus (left and right hippocampus) and gray matter volumes of the amygdala and frontal lobe were also reduced, but these differences were not significant. The functional studies revealed differences in brain region activation in response to stimuli in the post-traumatic stress symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD exhibited structural and functional brain abnormalities and that some of the abnormalities occurred in different brain regions than those observed in adults.


Assuntos
Encéfalo/diagnóstico por imagem , Imagem por Ressonância Magnética , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Encéfalo/patologia , Humanos , Tamanho do Órgão , Transtornos de Estresse Pós-Traumáticos/patologia
13.
Sci Rep ; 6: 38897, 2016 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-27941946

RESUMO

Neuroimaging-based models contribute to increasing our understanding of schizophrenia pathophysiology and can reveal the underlying characteristics of this and other clinical conditions. However, the considerable variability in reported neuroimaging results mirrors the heterogeneity of the disorder. Machine learning methods capable of representing invariant features could circumvent this problem. In this structural MRI study, we trained a deep learning model known as deep belief network (DBN) to extract features from brain morphometry data and investigated its performance in discriminating between healthy controls (N = 83) and patients with schizophrenia (N = 143). We further analysed performance in classifying patients with a first-episode psychosis (N = 32). The DBN highlighted differences between classes, especially in the frontal, temporal, parietal, and insular cortices, and in some subcortical regions, including the corpus callosum, putamen, and cerebellum. The DBN was slightly more accurate as a classifier (accuracy = 73.6%) than the support vector machine (accuracy = 68.1%). Finally, the error rate of the DBN in classifying first-episode patients was 56.3%, indicating that the representations learned from patients with schizophrenia and healthy controls were not suitable to define these patients. Our data suggest that deep learning could improve our understanding of psychiatric disorders such as schizophrenia by improving neuromorphometric analyses.


Assuntos
Encéfalo/patologia , Imagem por Ressonância Magnética , Modelos Neurológicos , Redes Neurais de Computação , Neuroimagem , Esquizofrenia/patologia , Máquina de Vetores de Suporte , Adulto , Área Sob a Curva , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Transtornos Psicóticos/diagnóstico , Curva ROC , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia
16.
J Psychiatr Res ; 71: 89-96, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26458012

RESUMO

Schizophrenia is a neurodevelopmental disorder that produces abnormalities across different brain regions. Measuring structural covariance with MRI is a well-established approach to investigate common changes in distinct systems. We investigated structural covariance in schizophrenia in a large Brazilian sample of individuals with chronic schizophrenia (n = 143), First Episode Psychosis (n = 32), and matched healthy controls (n = 82) using a combination of graph analysis and computational neuroanatomy. Firstly, we proposed the connectivity-closeness and integrity-closeness centrality measures and them compared healthy controls with chronic schizophrenia regarding these metrics. We then conducted a second analysis on the mapped regions comparing the pairwise difference between the three groups. Our results show that compared with controls, both patient groups (in pairwise comparisons) had a reduced integrity-closeness in pars orbitalis and insula, suggesting that the relationship between these areas and other brain regions is increased in schizophrenia. No differences were found between the First Episode Psychosis and Schizophrenia groups. Since in schizophrenia the brain is affected as a whole, this may mirror that these regions may be related to the generalized structural alteration seen in schizophrenia.


Assuntos
Encéfalo/patologia , Transtornos Psicóticos/patologia , Esquizofrenia/patologia , Doença Aguda , Adulto , Brasil , Doença Crônica , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Escalas de Graduação Psiquiátrica
17.
Psychiatry Res ; 234(1): 84-9, 2015 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-26341949

RESUMO

Brain-derived neurotrophic factor (BDNF) has been implicated in neuronal plasticity, a key process related to the pathophysiology of schizophrenia. However, the relationship of peripheral levels of BDNF to cortical thickness and subcortical structures has not been extensively investigated. This study aims to investigate the relationship of peripheral serum BDNF levels to cortical thickness and volumes of the hippocampus and amygdala. Twenty-nine patients with schizophrenia and 32 healthy controls were included in this study. Structural magnetic resonance imaging (MRI) scans obtained in a 1.5 T scanner were performed in all subjects. Images were processed using Freesurfer software. Blood samples were collected on the same day of the MRI scan for BDNF peripheral levels. Vertex-wise analysis revealed significantly thinner cortex in patients compared with controls. BDNF levels and cortical thickness showed different patterns of correlation for patients and healthy controls in one cluster in the right hemisphere distributed across the supramarginal, postcentral, and inferior frontal cortices.


Assuntos
Tonsila do Cerebelo/patologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Córtex Cerebral/patologia , Hipocampo/patologia , Esquizofrenia/sangue , Esquizofrenia/patologia , Adulto , Córtex Cerebral/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Tamanho do Órgão , Adulto Jovem
18.
Menopause ; 22(4): 444-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25268407

RESUMO

OBJECTIVE: This study aims to test the construct validity of the 11 items of the Kupperman index (KI), which has been pioneering in its attempt to quantify climacteric symptoms. METHODS: Unidimensional confirmatory factor analysis of the 11 graded items (hot flashes, paresthesia, insomnia, nervousness, melancholia, vertigo, weakness, arthralgia or myalgia, headache, palpitations, and formication), using a four-point scale (0, none; 4, severe), was used to evaluate the KI in a sample consisting of 84 women with a mean (SD) age of 54.34 (4.00) years who have been in menopause for a mean (SD) of 4.36 (2.53) years. RESULTS: The KI returned poor results on unidimensional model testing (root-mean-square error adjustment, 0.109; 90% CI, 0.075-0.142; comparative fit index, 0.871; Tucker Lewis index, 0.838; weighted root-mean-square residual, 0.971; χ(2)(44) = 87.599; P < 0.001), indicating that the set of items does not properly evaluate the underlying phenomena (climacteric symptoms). CONCLUSIONS: Our study verifies the poor fit of the KI and provides psychometric evidence that KI items warrant revision and/or that the concept underlying climacteric symptoms should be revisited.


Assuntos
Climatério/fisiologia , Menopausa/fisiologia , Psicometria/normas , Análise Fatorial , Feminino , Fogachos/diagnóstico , Humanos , Índice de Gravidade de Doença , Inquéritos e Questionários
19.
Cerebellum ; 14(2): 175-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25382714

RESUMO

Hereditary and sporadic cerebellar ataxias represent a vast and still growing group of diseases whose diagnosis and differentiation cannot only rely on clinical evaluation. Brain imaging including magnetic resonance (MR) and nuclear medicine techniques allows for characterization of structural and functional abnormalities underlying symptomatic ataxias. These methods thus constitute a potential source of radiological biomarkers, which could be used to identify these diseases and differentiate subgroups of them, and to assess their severity and their evolution. Such biomarkers mainly comprise qualitative and quantitative data obtained from MR including proton spectroscopy, diffusion imaging, tractography, voxel-based morphometry, functional imaging during task execution or in a resting state, and from SPETC and PET with several radiotracers. In the current article, we aim to illustrate briefly some applications of these neuroimaging tools to evaluation of cerebellar disorders such as inherited cerebellar ataxia, fetal developmental malformations, and immune-mediated cerebellar diseases and of neurodegenerative or early-developing diseases, such as dementia and autism in which cerebellar involvement is an emerging feature. Although these radiological biomarkers appear promising and helpful to better understand ataxia-related anatomical and physiological impairments, to date, very few of them have turned out to be specific for a given ataxia with atrophy of the cerebellar system being the main and the most usual alteration being observed. Consequently, much remains to be done to establish sensitivity, specificity, and reproducibility of available MR and nuclear medicine features as diagnostic, progression and surrogate biomarkers in clinical routine.


Assuntos
Doenças Cerebelares/diagnóstico , Doenças Cerebelares/patologia , Animais , Doenças Cerebelares/metabolismo , Cerebelo/metabolismo , Cerebelo/patologia , Consenso , Humanos , Neuroimagem/métodos
20.
Front Behav Neurosci ; 8: 342, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25339875

RESUMO

BACKGROUND: Children exposed to early life stress (ELS) exhibit enlarged amygdala volume in comparison to controls. The primary goal of this study was to examine amygdala volumes in bonnet macaques subjected to maternal variable foraging demand (VFD) rearing, a well-established model of ELS. Preliminary analyses examined the interaction of ELS and the serotonin transporter gene on amygdala volume. Secondary analyses were conducted to examine the association between amygdala volume and other stress-related variables previously found to distinguish VFD and non-VFD reared animals. METHODS: Twelve VFD-reared and nine normally reared monkeys completed MRI scans on a 3T system (mean age = 5.2 years). RESULTS: Left amygdala volume was larger in VFD vs. control macaques. Larger amygdala volume was associated with: "high" cerebrospinal fluid concentrations of corticotropin releasing-factor (CRF) determined when the animals were in adolescence (mean age = 2.7 years); reduced fractional anisotropy (FA) of the anterior limb of the internal capsule (ALIC) during young adulthood (mean age = 5.2 years) and timid anxiety-like responses to an intruder during full adulthood (mean age = 8.4 years). Right amygdala volume varied inversely with left hippocampal neurogenesis assessed in late adulthood (mean age = 8.7 years). Exploratory analyses also showed a gene-by-environment effect, with VFD-reared macaques with a single short allele of the serotonin transporter gene exhibiting larger amygdala volume compared to VFD-reared subjects with only the long allele and normally reared controls. CONCLUSION: These data suggest that the left amygdala exhibits hypertrophy after ELS, particularly in association with the serotonin transporter gene, and that amygdala volume variation occurs in concert with other key stress-related behavioral and neurobiological parameters observed across the lifecycle. Future research is required to understand the mechanisms underlying these diverse and persistent changes associated with ELS and amygdala volume.

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