RESUMO
Brain development during childhood and early adolescence is characterized by global changes in brain architecture. Neuroimaging studies have revealed overall decreases in cortical thickness (CT) and increases in fractional anisotropy (FA). Furthermore, previous studies have shown that certain cortical regions display coordinated growth during development. However, there is significant heterogeneity in the timing and speed of these developmental transformations, and it is still unclear whether white and grey matter changes are co-localized. In this multimodal neuroimaging study, we investigated the relationship between grey and white matter developmental changes and asynchronous maturation within brain regions in 249 normally developing children between the ages 7-14. We used structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to analyze CT and FA, respectively, as well as their covariance across development. Consistent with previous studies, we observed overall cortical thinning with age, which was accompanied by increased FA. We then compared the coordinated development of grey and white matter as indexed by covariance measures. Covariance between grey matter regions and the microstructure of white matter tracts connecting those regions were highly similar, suggesting that coordinated changes in the cortex were mirrored by coordinated changes in their respective tracts. Examining within-brain divergent trajectories, we found significant structural decoupling (decreased covariance) between several brain regions and tracts in the 9- to 11-year-old group, particularly involving the forceps minor and the regions that it connects to. We argue that this decoupling could reflect a developmental pattern within the prefrontal region in 9- and 11-year-old children, possibly related to the significant changes in cognitive control observed at this age.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/crescimento & desenvolvimento , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Adolescente , Criança , Estudos Transversais , Imagem de Difusão por Ressonância Magnética , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Imagem Multimodal , Tamanho do ÓrgãoRESUMO
Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.
Assuntos
Transtorno Bipolar/genética , Regulação da Expressão Gênica/genética , Transtornos Psicóticos/genética , Esquizofrenia/genética , Psicologia do Esquizofrênico , Adulto , Proteínas de Transporte/genética , Estudos de Casos e Controles , RNA Helicases DEAD-box/genética , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Proteína Básica da Mielina/genética , Proteínas Proto-Oncogênicas c-akt/genética , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Psicometria , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/psicologia , Valores de Referência , Ribonuclease III/genética , Esquizofrenia/diagnóstico , Estatística como Assunto , Adulto JovemRESUMO
OBJECTIVE: To investigate the association between peripheral biomarkers and child psychopathology in a large community sample. METHOD: A total of 625 aged 6- to 13-year old subjects were recruited from a community school-based study. Psychopathology was assessed using the Child Behaviour Checklist (CBCL). Psychiatric diagnosis was evaluated using the Development and Well-Being Assessment. The following biomarkers were examined in peripheral blood: brain-derived neurotrophic factor, cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-g, and TNF-α), chemokines (eotaxin/CCL11, IP-10, MCP-1), cytokine receptors (sTNFR1 and sTNFR2), and the oxidative stress marker TBARS. RESULTS: We found significant associations between sTNFR2, eotaxin/CCL11 and CBCL total score, as well as with specific dimensions of psychopathology. There were different patterns of association between these biomarkers and psychological and behavioural symptoms in children with and without a mental disorder. TBARS, IL-6 and MCP-1 were more specific to some clusters of symptoms in children with a psychiatric diagnosis. CONCLUSION: Our data support the potential use of biomarkers, especially those involved in immune-inflammatory pathways, in investigating neurodevelopmental psychopathology. Their association with different dimensions of symptoms might be of useful when analyzing illness severity and clusters of symptoms within specific disorders.
RESUMO
In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=-5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=-0.247; P=0.004) and Hopkins total (r=-0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations.
Assuntos
Transtornos Cognitivos/sangue , Transtornos Cognitivos/complicações , Peptidil Dipeptidase A/sangue , Esquizofrenia/sangue , Esquizofrenia/complicações , Adolescente , Adulto , Idoso , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: To verify the association between violence and alcohol dependence syndrome in sample populations. METHOD: Population-wide survey with multistage probabilistic sample. 3,744 individuals of both genders, aged from 15 to 75 years, were interviewed from the cities of São Paulo and Rio de Janeiro using the Composite International Diagnostic Interview (CIDI 2.1). RESULTS: In both cities, alcohol dependence was associated with the male gender, having suffered violence related to criminality, and having suffered familial violence. In both cities, urban violence, in more than 50% of cases, and familial violence, in more than 90% of cases, preceded alcohol dependence. The reoccurrence of traumatic events occurred in more than half of individuals dependent on alcohol. In São Paulo, having been diagnosed with PTSD is associated with violence revictimization (P = 0.014; Odds = 3.33). CONCLUSION: Alcohol dependence syndrome is complexly related to urban and familial violence in the general population. Violence frequently precedes alcoholism, but this relationship is dependent on residence and traumatic events. This vicious cycle contributes to perpetuating the high rates of alcoholism and violence in the cities. Politicians ordering the reduction of violence in the large metropolises can, potentially, reduce alcoholism and contribute to the break of this cycle.
Assuntos
Alcoolismo/diagnóstico , Alcoolismo/epidemiologia , Vítimas de Crime/estatística & dados numéricos , Violência/estatística & dados numéricos , Adolescente , Adulto , Idoso , Alcoolismo/psicologia , Brasil/epidemiologia , Vítimas de Crime/psicologia , Demografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto JovemRESUMO
The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.
RESUMO
The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.
RESUMO
OBJECTIVES: To assess the influence of total or selective REM sleep deprivation on the dopamine transporter (DAT) densities and sleep patterns of healthy volunteers. DESIGN: Prospective study. SETTING: Evaluation of polysomnography recordings and DAT density after 4 nights of selective REM sleep deprivation followed by 3 nights of sleep recovery compared to a control group and a group that was subjected to 2 nights of total sleep deprivation. Single positron emission computed tomography and [99mTc]TRODAT-1 were used to assess the cerebral DAT density in the striatum at baseline, after REM sleep deprivation and total sleep deprivation as well as after sleep recovery. Blood was collected daily to examine prolactin and estradiol levels, which were correlated with dopaminergic activity. PATIENTS OR PARTICIPANTS: Thirty healthy male volunteers ranging from 19 to 29 years of age were randomly assigned to one of three experimental groups after giving written informed consent (10 non-sleep deprived, 10 total sleep deprived, and 10 REM sleep deprived). MEASUREMENTS AND RESULTS: Four nights of REM sleep deprivation and 2 nights of total sleep deprivation induced distinct and heterogeneous patterns of sleep recovery. No significant modulation of DAT availability was observed within groups. In the recovery nights, changes in cortisol, prolactin and estradiol concentrations were significantly correlated with specific sleep stages in the total and REM sleep deprived groups. In addition, DAT density was positively correlated with estradiol concentration and inversely associated with SWS latency only after total sleep deprivation. CONCLUSION: Our study demonstrates that although sleep deprivation did not promote significant alterations in DAT density within the striatum, there were significant correlations among transporter availability, hormonal concentrations and sleep parameters.
Assuntos
Corpo Estriado/diagnóstico por imagem , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Privação do Sono/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único , Adulto , Mapeamento Encefálico , Estradiol/sangue , Humanos , Masculino , Compostos de Organotecnécio , Polissonografia , Prolactina/sangue , Valores de Referência , Fases do Sono/fisiologia , Tropanos , Vigília/fisiologia , Adulto JovemRESUMO
The adaptive behavior of human beings is usually supported by rapid monitoring of outstanding events in the environment. Some investigators have suggested that a primary attention deficit might trigger symptoms of schizophrenia. In addition, researchers have long discussed the relationship between schizophrenia and the schizophrenia-like psychosis of epilepsy (SLPE). On the basis of these considerations, the objective of the present study was to investigate attention performance of patients with both disorders. Patient age was 18 to 60 years, and all patients had received formal schooling for at least four years. Patients were excluded if they had any systemic disease with neurologic or psychiatric comorbidity, or a history of brain surgery. The computer-assisted TAVIS-2R test was applied to all patients and to a control group to evaluate and discriminate between selective, alternating and sustained attention. The TAVIS-2R test is divided into three parts: one for selective attention (5 min), the second for alternating attention (5 min), and the third for the evaluation of vigilance or sustained attention (10 min). The same computer software was used for statistical analysis of reaction time, omission errors, and commission errors. The sample consisted of 36 patients with schizophrenia, 28 with interictal SLPE, and 47 healthy controls. The results of the selective attention tests for both patient groups were significantly lower than that for controls. The patients with schizophrenia and SLPE performed differently in the alternating and sustained attention tests: patients with SLPE had alternating attention deficits, whereas patients with schizophrenia showed deficits in sustained attention. These quantitative results confirmed the qualitative clinical observations for both patient groups, that is, that patients with schizophrenia had difficulties in focusing attention, whereas those with epilepsy showed perseveration in attention focus.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção/fisiologia , Epilepsia/psicologia , Psicologia do Esquizofrênico , Esquizofrenia/fisiopatologia , Fatores Etários , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/fisiopatologia , Escolaridade , Epilepsia/diagnóstico , Testes de Inteligência , Modelos Lineares , Testes Neuropsicológicos , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/diagnósticoRESUMO
BACKGROUND: Kleine-Levin syndrome (KLS) is a rare disorder whose pathophysiological mechanisms remain unknown. PATIENTS AND METHODS: To investigate dopamine abnormalities in KLS, a [99mTc]-TRODAT-1 single photon emission computerized tomography (SPECT) was performed in a patient with KLS during the asymptomatic period and compared with three matched healthy controls. RESULTS: The patient had 14% lower striatal dopamine transporter binding potential (DAT-BP) compared to the mean DAT-BP of three healthy controls. CONCLUSION: This study provides in vivo evidence for abnormalities in the DAT-BP, suggesting an involvement of the dopaminergic system in the pathophysiology of KLS.