RESUMO
Only a small number of studies have assessed structural differences between the two hemispheres during childhood and adolescence. However, the existing findings lack consistency or are restricted to a particular brain region, a specific brain feature, or a relatively narrow age range. Here, we investigated associations between brain asymmetry and age as well as sex in one of the largest pediatric samples to date (n = 4265), aged 1-18 years, scanned at 69 sites participating in the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium. Our study revealed that significant brain asymmetries already exist in childhood, but their magnitude and direction depend on the brain region examined and the morphometric measurement used (cortical volume or thickness, regional surface area, or subcortical volume). With respect to effects of age, some asymmetries became weaker over time while others became stronger; sometimes they even reversed direction. With respect to sex differences, the total number of regions exhibiting significant asymmetries was larger in females than in males, while the total number of measurements indicating significant asymmetries was larger in males (as we obtained more than one measurement per cortical region). The magnitude of the significant asymmetries was also greater in males. However, effect sizes for both age effects and sex differences were small. Taken together, these findings suggest that cerebral asymmetries are an inherent organizational pattern of the brain that manifests early in life. Overall, brain asymmetry appears to be relatively stable throughout childhood and adolescence, with some differential effects in males and females.
Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Caracteres Sexuais , Humanos , Adolescente , Masculino , Criança , Feminino , Pré-Escolar , Lactente , Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Encéfalo/anatomia & histologia , Fatores Etários , Desenvolvimento Infantil/fisiologia , Lateralidade Funcional/fisiologia , Desenvolvimento do Adolescente/fisiologiaRESUMO
The corpus callosum is the largest white matter tract in the human brain connecting and coordinating homologous regions of the right and left hemispheres and has been strongly implicated in the pathogenesis of psychosis. We investigated corpus callosum morphology in a large community cohort of 917 individuals (aged 8-21), including 267 endorsing subsyndromal or threshold psychotic symptoms (207 on the psychosis spectrum and 60 with limited psychosis based on previously published criteria) and 650 non-psychotic volunteers. We used a highly reliable and previously published algorithm to automatically identify the midsagittal plane and to align the corpus callosum along the anterior and posterior commissures for segmentation, thereby eliminating these sources of error variance in dependent measures, which included perimeter, length, mean thickness and shape (circularity). The parcellation scheme divided the corpus callosum into 7 subregions that consisted of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Both individuals endorsing psychotic symptoms and those with limited psychosis had significantly (p<.05) smaller area and lower thickness measures compared to healthy volunteers, but did not differ significantly from each other. Findings were relatively widespread indicating a relatively global effect not circumscribed to any particular corpus callosum subregion. These data are consistent with the hypothesis that corpus callosum abnormalities may be evident early in the course of illness and predate the onset of frank psychosis. Given that these measures can be easily obtained and are highly reliable they may assist in the identification of individuals at future risk for psychosis.
Assuntos
Corpo Caloso/diagnóstico por imagem , Imageamento por Ressonância Magnética , Transtornos Psicóticos/diagnóstico por imagem , Adolescente , Algoritmos , Criança , Estudos de Coortes , Corpo Caloso/crescimento & desenvolvimento , Corpo Caloso/patologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Tamanho do Órgão , Reconhecimento Automatizado de Padrão , Sintomas Prodrômicos , Transtornos Psicóticos/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Substância Branca/patologia , Adulto JovemRESUMO
Free Water Imaging is a novel diffusion magnetic resonance (MR) imaging method that is able to separate changes affecting the extracellular space from those that reflect changes in neuronal cells and processes. A previous Free Water Imaging study in schizophrenia identified significantly greater extracellular water volume in the early stages of the disorder; however, its clinical and functional sequelae have not yet been investigated. Here, we applied Free Water Imaging to a larger cohort of 63 first-episode patients with psychosis and 70 healthy matched controls to better understand the functional significance of greater extracellular water. We used diffusion MR imaging data and the Tract-Based Spatial Statistics analytic pipeline to first analyze fractional anisotropy (FA), the most commonly employed metric for assessing white matter. This comparison was then followed by Free Water Imaging analysis, where two parameters, the fractional volume of extracellular free-water (FW) and cellular tissue FA (FA-t), were estimated and compared across the entire white matter skeleton between groups, and correlated with cognitive measures at baseline and following 12 weeks of antipsychotic treatment. Our results indicated lower FA across the whole brain in patients compared with healthy controls that overlap with significant increases in FW, with only limited decreases in FA-t. In addition, higher FW correlated with better neurocognitive functioning following 12 weeks of antipsychotic treatment. We believe this is the first study to suggest that an extracellular water increase during the first-episode of psychosis, which may be indicative of an acute neuroinflammatory process, and/or cerebral edema may predict better functional outcome.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/patologia , Adulto , Antipsicóticos/uso terapêutico , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Espaço Extracelular/diagnóstico por imagem , Feminino , Previsões/métodos , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Transtornos Neurocognitivos/diagnóstico por imagem , Esquizofrenia/patologia , Resultado do Tratamento , Água/análise , Substância Branca/patologia , Adulto JovemRESUMO
BACKGROUND: Hippocampal dysfunction is considered central to many neurobiological models of schizophrenia, yet there are few longitudinal in vivo neuroimaging studies that have investigated the relationship between antipsychotic treatment and morphologic changes within specific hippocampal subregions among patients with psychosis. METHOD: A total of 29 patients experiencing a first episode of psychosis with little or no prior antipsychotic exposure received structural neuroimaging examinations at illness onset and then following 12 weeks of treatment with either risperidone or aripiprazole in a double-blind randomized clinical trial. In addition, 29 healthy volunteers received structural neuroimaging examinations at baseline and 12-week time points. We manually delineated six hippocampal subregions [i.e. anterior cornu ammonis (CA) 1-3, posterior CA1-3, subiculum, dentate gyrus/CA4, entorhinal cortex, and fimbria] from 3T magnetic resonance images using an established method with high inter- and intra-rater reliability. RESULTS: Following antipsychotic treatment patients demonstrated significant reductions in dentate gyrus/CA4 volume and increases in subiculum volume. Healthy volunteers demonstrated non-significant volumetric changes in these subregions across the two time points. We observed a significant quadratic (i.e. inverted U) association between changes in dentate gyrus/CA4 volume and cumulative antipsychotic dosage between the scans. CONCLUSIONS: This study provides the first evidence to our knowledge regarding longitudinal in vivo volumetric changes within specific hippocampal subregions in patients with psychosis following antipsychotic treatment. The finding of a non-linear relationship between changes in dentate gyrus/CA4 subregion volume and antipsychotic exposure may provide new avenues into understanding dosing strategies for therapeutic interventions relevant to neurobiological models of hippocampal dysfunction in psychosis.
Assuntos
Antipsicóticos/farmacologia , Aripiprazol/farmacologia , Hipocampo , Transtornos Psicóticos/tratamento farmacológico , Risperidona/farmacologia , Adulto , Antipsicóticos/administração & dosagem , Aripiprazol/administração & dosagem , Giro Denteado/diagnóstico por imagem , Giro Denteado/efeitos dos fármacos , Giro Denteado/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Risperidona/administração & dosagem , Adulto JovemRESUMO
Genome-wide association studies have provided strong evidence for association of the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder. Neuroimaging studies have suggested that variation at rs1344706 may be associated with neural endophenotypes such as white matter volumes and densities. However, analyses of white matter microstructure using diffusion tensor imaging (DTI) have produced conflicting results. We examined the association between rs1344706 and white matter microstructure in 107 healthy individuals using tract-based spatial statistics (TBSS). TBSS analysis showed significant association between the risk allele and lower fractional anisotropy in the corpus callosum, left forceps minor, and right parietal white matter (p<.05; FWE corrected). Post-hoc analyses indicated that this association was largely driven by alterations in radial diffusivity, consistent with an effect of genotype on myelination. In light of the strong DTI evidence for white matter microstructural abnormalities in schizophrenia, the current results implicate a potential mechanism for schizophrenia risk formation by ZNF804A rs1344706 genotype.
Assuntos
Encéfalo/anatomia & histologia , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Substância Branca/anatomia & histologia , Adolescente , Adulto , Idoso , Anisotropia , Criança , Imagem de Difusão por Ressonância Magnética , Feminino , Lateralidade Funcional/genética , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N=27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N=17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Hipocampo/patologia , Esquizofrenia/genética , Esquizofrenia/patologia , Adulto , Substituição de Aminoácidos , Feminino , Lateralidade Funcional , Hipocampo/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Tamanho do Órgão , Polimorfismo de Nucleotídeo Único/genética , Valores de Referência , Fatores de Risco , Método Simples-Cego , Estatísticas não ParamétricasRESUMO
Psychophysiologic studies use air puff as an aversive stimulus to document abnormal fear conditioning in children of parents with anxiety disorders. This study used functional magnetic resonance imaging (fMRI) to examine changes in amygdala activity during air-puff conditioning among adults. Blood oxygen level-dependent (BOLD) signal was monitored in seven adults during 16 alternating presentations of two different colored lights (CS+ vs. CS-), one of which was consistently paired with an aversive air puff. A region-of-interest analysis demonstrated differential change in BOLD signal in the right but not left amygdala across CS+ versus CS- viewing. The amygdala is engaged by pairing of a light with an air puff. Given that prior studies relate air-puff conditioning to risk for anxiety in children, these methods may provide an avenue for directly studying the developmental neurobiology of fear conditioning.
Assuntos
Tonsila do Cerebelo/fisiopatologia , Transtornos de Ansiedade/fisiopatologia , Transtornos de Ansiedade/psicologia , Condicionamento Clássico/fisiologia , Medo , Adulto , Tonsila do Cerebelo/metabolismo , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/metabolismoRESUMO
Face-emotion processing has shown signs of developmental change during adolescence. Functional magnetic resonance imaging (fMRI) was used on 10 adolescents and 10 adults to contrast brain regions engaged by a masked emotional-face task (viewing a fixation cross and a series of masked happy and masked fearful faces), while blood oxygen level dependent signal was monitored by a 1.5-T MRI scanner. Brain regions differentially engaged in the 2 age groups were mapped by using statistical parametric mapping. Summed across groups, the contrast of masked face versus fixation-cross viewing generated activations in occipital-temporal regions previously activated in passive face-viewing tasks. Adolescents showed higher maxima for activations in posterior association cortex for 3 of the 4 statistical contrasts. Adolescents and adults differed in the degree to which posterior hemisphere brain areas were engaged by viewing masked facial displays of emotion.
Assuntos
Afeto , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/fisiologia , Expressão Facial , Imageamento por Ressonância Magnética , Mascaramento Perceptivo , Percepção Visual/fisiologia , Adolescente , Adulto , Fatores Etários , Criança , Feminino , Humanos , MasculinoRESUMO
Although frontal lobe structural and functional abnormalities have been identified in schizophrenia, their relationship remains elusive. Because the frontal lobes are both structurally and functionally heterogeneous, it is possible that some measures of frontal lobe structure may not have accurately identified relevant frontal lobe subregions. The authors hypothesized that the volumes of two dorsal, 'archicortical' subregions (i.e. superior frontal gyrus and anterior cingulate gyrus), but not a ventral, 'paleocortical' subregion (i.e. orbital frontal region) would be significantly and selectively correlated with executive and motor dysfunction in patients with schizophrenia as previously reported for the anterior hippocampal region. Volumes of these frontal lobe subregions were measured from magnetic resonance images based on sulcal anatomy in 20 men and 15 women with first-episode schizophrenia. All patients completed a comprehensive neuropsychological test battery while clinically stabilized that encompassed six domains of functioning: attention, executive, motor, visuospatial, memory and language. Findings indicated that reduced anterior cingulate gyrus volume was significantly correlated with worse executive functioning in men; among women, there were no significant correlations. Among men, anterior cingulate gyrus volume was significantly more strongly correlated with executive functioning than with attention, visuospatial, memory, language and general intellectual functioning. Neither executive nor motor functioning was significantly more strongly correlated with the dorsal 'archicortical' volumes than with orbital frontal volume. These findings suggest a link between executive deficits and dysfunction of the dorsal 'archicortical' system and implicate sex differences in their relationship in first-episode schizophrenia.
Assuntos
Giro do Cíngulo/patologia , Imageamento por Ressonância Magnética , Esquizofrenia/diagnóstico , Adulto , Mapeamento Encefálico , Dominância Cerebral/fisiologia , Feminino , Lobo Frontal/patologia , Humanos , Masculino , Testes Neuropsicológicos , Valores de Referência , Psicologia do Esquizofrênico , Fatores SexuaisRESUMO
BACKGROUND: Functional neuroimaging studies have implicated the frontal lobes and the hippocampus-amygdala complex in the pathophysiology of obsessive-compulsive disorder (OCD). These brain regions have not been well investigated in patients with OCD, however, using magnetic resonance imaging. METHODS: Volumes of the superior frontal gyrus, anterior cingulate gyrus, orbital frontal region, hippocampus, and amygdala were computed from contiguous magnetic resonance images in a sample of 26 patients with OCD and 26 healthy comparison subjects. RESULTS: Patients with OCD had significantly reduced bilateral orbital frontal and amygdala volumes compared with healthy comparison subjects and lacked the normal hemispheric asymmetry of the hippocampus-amygdala complex. Neither brain structure volumes nor asymmetry indices were significantly correlated with total illness duration or length of current OCD episode. CONCLUSIONS: Findings of reduced orbital frontal and amygdala volumes in patients implicate a structural abnormality of these brain regions in the pathophysiology of OCD. Absence of the normal hemispheric asymmetry of the hippocampus-amygdala complex in patients is consistent with an anomalous neurodevelopmental process.
Assuntos
Tonsila do Cerebelo/anatomia & histologia , Lobo Frontal/anatomia & histologia , Imageamento por Ressonância Magnética , Transtorno Obsessivo-Compulsivo/diagnóstico , Adulto , Tonsila do Cerebelo/fisiopatologia , Feminino , Lobo Frontal/fisiopatologia , Lateralidade Funcional/fisiologia , Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/fisiopatologia , Hipocampo/anatomia & histologia , Hipocampo/fisiopatologia , Humanos , Masculino , Transtorno Obsessivo-Compulsivo/fisiopatologiaRESUMO
The evidence for frontal lobe structural abnormalities in schizophrenia using magnetic resonance (MR) imaging has been mixed, but most studies used either single slice measures or total volumes of a single frontal region, neither of which is sensitive to potential volume differences in more specific subregions. This study employed reliable methods for parcellation of the frontal lobes from MR images based on the sulcal anatomy. Following a cytoarchitectonic theory that distinguishes dorsomedial (archicortically derived) from ventrolateral (paleocortically derived) frontal subregions, we measured the superior frontal gyrus, anterior cingulate gyrus, and orbital frontal region in 19 first-episode schizophrenia patients and 26 healthy comparison subjects. Results indicated that male patients had significantly larger right orbital frontal volume compared to their left orbital frontal volume and compared to healthy men. Among male patients larger right orbital frontal volume was significantly correlated with smaller right 'archicortical' (i.e. anterior cingulate and superior frontal gyri) volume. Furthermore, the ratio of right orbital frontal to right 'archicortical' volume was significantly and positively correlated with level of delusions among male patients. These findings suggest that there may be reciprocal controls on 'archicortical' and 'paleocortical' neurodevelopment among men with schizophrenia, and that larger paleocortical relative to archicortical volumes may be associated with increased delusions.
Assuntos
Lobo Frontal/patologia , Esquizofrenia/patologia , Encéfalo/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Fatores de TempoRESUMO
BACKGROUND: Some studies have reported psychotic symptom exacerbation during "pharmacologic challenge" paradigms using dopamine agonists. Few studies, however, have examined the effects of these agonists on neurocognitive functions in patients with schizophrenia. This study assessed the effects of methylphenidate infusion on an oral word production test with demonstrated sensitivity to frontal lobe lesions, and on clinical state. METHODS: Patients were tested at two different phases; at the onset of their first-episode of schizophrenia (acute phase), and then again after they had responded to treatment and were clinically stable (stabilization phase). During each phase, patients were tested prior to and following methylphenidate infusion. Symptom clusters (i.e., positive, negative, and disorganization) were formed from SANS and SADS-C (+PD) ratings at each of these four timepoints. RESULTS: Patients produced significantly more words at preinfusion and while stabilized, suggesting that overall, decreased dopamine activity was associated with better word production. Redundant errors (i.e., perseverations of previously mentioned words and production of multiple words with the same roots) increased significantly following infusion in the stabilized phase. Disorganization symptoms increased significantly following infusion, regardless of study phase. CONCLUSIONS: These findings are consistent with previous theoretical and empirical findings relating dopamine activity to verbal output, a "redundancy bias" in cognitive control, and exacerbation of disorganization symptoms.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Metilfenidato/farmacologia , Esquizofrenia/diagnóstico , Fala/efeitos dos fármacos , Comportamento Verbal/efeitos dos fármacos , Adulto , Análise de Variância , Feminino , Humanos , Injeções Intravenosas , Estudos Longitudinais , Masculino , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
Handedness questionnaire items from the General Scale of the Lateral Preference Schedule (Dean, 1988) were administered to 423 intellectually gifted and 226 nongifted children to investigate the underlying processes that contribute to laterality. Handedness items were factor analyzed using principal components (PC) analysis with varimax rotation. PC analyses computed separately for gifted and nongifted left and right-handed writers yielded very different factor structures. Left-handers (regardless of gifted status) tended to have factor structures marked by items that loaded saliently on more than one factor. Whereas a four factor solution best fit the data for the nongifted left-handers, a three factor solution was the best fit for the gifted left-handed children. The factor structure for the left-handed gifted children was marked by two factors where the item "draw" was the only item to load both positively and saliently, a pattern not evident among the nongifted left-handers. These results suggested different underlying patterns contributing to laterality among these groups of children.
Assuntos
Criança Superdotada/psicologia , Lateralidade Funcional , Criança , Feminino , Humanos , Masculino , Desempenho Psicomotor , Escalas de WechslerRESUMO
This study investigated high school students' marijuana usage patterns in relation to their harmfulness ratings of 15 licit and illicit drugs, perceived negative consequences from using marijuana, and types of defense mechanisms employed. Subjects were classified into one of five pattern-of-use groups based on marijuana usage: principled nonusers, nonusers, light users, moderate users, and heavy users. Principled nonusers (individuals who have never used marijuana and would not do so if it was legalized) rated marijuana, hashish, cocaine, and alcohol as significantly more harmful than heavy users. A cluster analysis of the drugs' harmfulness ratings best fit a three cluster solution and were named medicinal drugs, recreational drugs, and hard drugs. In general, principled nonusers rated negative consequences from using marijuana as significantly more likely to occur than other groups. Principled nonusers and heavy users utilized reversal from the Defense Mechanism Inventory, which includes repression and denial, significantly more than nonusers, indicating some trait common to the two extreme pattern-of-use groups.