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BACKGROUND: A structural neuroanatomical change indicating a reduction in brain tissue is a notable feature of schizophrenia. Several pathophysiological processes such as aberrant cortical maturation, progressive tissue loss and compensatory tissue increase could contribute to the structural changes seen in schizophrenia. METHOD: We studied cortical thickness using surface-based morphometry in 98 clinically stable patients with schizophrenia and 83 controls. Using a pattern classification approach, we studied whether the features that discriminate patients from controls vary across the different stages of the illness. Using a covariance analysis, we also investigated if concurrent increases accompany decreases in cortical thickness. RESULTS: Very high levels of accuracy (96.3%), specificity (98.8%) and sensitivity (88%) were noted when classifying patients with <2 years of illness from controls. Within the patient group, reduced thickness was consistently accompanied by increased thickness in distributed brain regions. A pattern of cortical amelioration or normalization (i.e. reduced deviation from controls) was noted with increasing illness duration. While temporo-limbic and fronto-parietal regions showed reduced thickness, the occipital cortex showed increased thickness, especially in those with a long-standing illness. CONCLUSION: A compensatory remodelling process might contribute to the cortical thickness variations in different stages of schizophrenia. Subtle cerebral reorganization reflecting the inherent plasticity of brain may occur concomitantly with processes contributing to tissue reduction in adult patients with schizophrenia.
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Corteza Cerebral/patología , Progresión de la Enfermedad , Imagen por Resonancia Magnética/métodos , Plasticidad Neuronal/fisiología , Esquizofrenia/patología , Máquina de Vectores de Soporte , Adulto , Corteza Cerebral/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Esquizofrenia/diagnóstico por imagen , Esquizofrenia/fisiopatología , Sensibilidad y Especificidad , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: There is an appreciable overlap in the clinical presentation, epidemiology and treatment response of the two major psychotic disorders - schizophrenia and bipolar disorder. Nevertheless, the shared neurobiological correlates of these two disorders are still elusive. Using diffusion tensor imaging (DTI), we sought to identify brain regions which share altered white-matter connectivity across a clinical spectrum of psychotic disorders. METHOD: A sample of 41 healthy controls, 62 patients in a clinically stable state of an established psychotic disorder (40 with schizophrenia, 22 with bipolar disorder) were studied using DTI. Tract-based spatial statistics (TBSS) was used in order to study group differences between patients with psychosis and healthy controls using fractional anisotropy (FA). Probabilistic tractography was used in order to visualize the clusters that showed significant differences between these two groups. RESULTS: The TBSS analysis revealed five clusters (callosal, posterior thalamic/optic, paralimbic, fronto-occipital) with reduced FA in psychosis. This reduction in FA was associated with an increase in radial diffusivity and a decrease in mode of anisotropy. Factor analysis revealed a single white-matter integrity factor that predicted social and occupational functioning scores in patients irrespective of the diagnostic categorization. CONCLUSIONS: Our results show that a shared white-matter dysconnectivity links the two major psychotic disorders. These microstructural abnormalities predict functional outcome better than symptom-based diagnostic boundaries during a clinically stable phase of illness, highlighting the importance of seeking shared neurobiological factors that underlie the clinical spectrum of psychosis.
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Trastorno Bipolar/patología , Imagen de Difusión Tensora/métodos , Red Nerviosa/patología , Trastornos Psicóticos/patología , Esquizofrenia/patología , Sustancia Blanca/patología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Patients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD. AIMS: To test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities. METHOD: A multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy controls. RESULTS: The MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus). CONCLUSIONS: This is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.
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Encéfalo/fisiopatología , Trastorno Depresivo Mayor/fisiopatología , Red Nerviosa/fisiopatología , Adulto , Encéfalo/patología , Mapeo Encefálico , Trastorno Depresivo Mayor/patología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/patología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Neuroimagen , Adulto JovenRESUMEN
Transcranial magnetic stimulation (TMS) is an FDA-approved neuromodulation treatment for major depressive disorder (MDD), thought to work by altering dysfunctional brain connectivity pathways, or by indirectly modulating the activity of subcortical brain regions. Clinical response to TMS remains highly variable, highlighting the need for baseline predictors of response and for understanding brain changes associated with response. This systematic review examined brain connectivity features, and changes in connectivity features, associated with clinical improvement following TMS in MDD. Forty-one studies met inclusion criteria, including 1097 people with MDD. Most studies delivered one of two types of TMS to left dorsolateral prefrontal cortex and measured connectivity using resting-state functional MRI. The subgenual anterior cingulate cortex was the most well-studied brain region, particularly its connectivity with the TMS target or with the "executive control network" of brain regions. There was marked heterogeneity in findings. There is a need for greater understanding of how cortical TMS modulates connectivity with, and the activity of, subcortical regions, and how these effects change within and across treatment sessions.
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Trastorno Depresivo Mayor , Imagen por Resonancia Magnética , Estimulación Magnética Transcraneal , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/fisiopatología , Estimulación Magnética Transcraneal/métodos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatologíaRESUMEN
Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive brain stimulation treatment for major depressive disorder, but there is marked inter-individual variability in response. Using latent class growth analysis with session-by-session patient global impression ratings from the recently completed BRIGhTMIND trial, we identified five distinct classes of improvement trajectory during a 20-session treatment course. This included a substantial class of patients noticing delayed onset of improvement. Contrary to prior expectations, members of a class characterised by early and continued improvement showed greatest inter-session variability in stimulated location. By relating target locations and inter-session variability to a well-studied atlas, we estimated an average of 3.0 brain networks were stimulated across the treatment course in this group, compared to 1.1 in a group that reported symptom worsening (p < 0.001, d = 0.893). If confirmed, this would suggest that deliberate targeting of multiple brain networks could be beneficial to rTMS outcomes.
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BACKGROUND: Recent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence. Method Baseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patients versus controls and recurrence versus non-recurrence versus control groups. RESULTS: Analysis of patients (n = 20) versus controls (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence. CONCLUSIONS: Convergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.
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Trastorno Depresivo Mayor/fisiopatología , Giro del Cíngulo/fisiopatología , Corteza Prefrontal/fisiopatología , Adulto , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Neuroimagen Funcional , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Recurrencia , Adulto JovenRESUMEN
BACKGROUND: Studying the distribution of anatomical abnormalities over the entire cortical surface can help to identify key neural circuits implicated in generating symptoms of neuropsychiatric disorders. There is a significant inconsistency among studies investigating the neuroanatomy of obsessive-compulsive disorder (OCD) because of the confounding influence of co-morbid depression and medication use and the lack of unbiased estimation of whole-brain morphometric changes. It is also unknown whether the distinct surface anatomical properties of thickness, surface area and gyrification, which collectively contribute to grey matter volume (GMV), are independently affected in OCD. Method The cortical maps of thickness, gyrification and surface areal change were acquired from 23 unmedicated OCD patients and 20 healthy controls using an unbiased whole-brain surface-based morphometric (SBM) method to detect regional changes in OCD. Subcortical structures were not assessed in this study. RESULTS: Patients showed a significant increase in the right inferior parietal cortical thickness. Significant increases in gyrification were also noted in the left insula, left middle frontal and left lateral occipital regions extending to the precuneus and right supramarginal gyrus in OCD. Areal contraction/expansion maps revealed no significant regional differences between the patients and controls. In patients, gyrification of the insula significantly predicted the symptom severity measured using Yale-Brown Obsessive-Compulsive Scale (YBOCS). CONCLUSIONS: An alteration in the cortical surface anatomy is an important feature of OCD seen in unmedicated samples that relates to the severity of the illness. The results underscore the presence of a neurodevelopmental aberration underlying the pathophysiology of OCD.
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Mapeo Encefálico/métodos , Corteza Cerebral/patología , Trastorno Obsesivo Compulsivo/patología , Adolescente , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Modelos Lineales , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Método de Montecarlo , Tamaño de los Órganos , Lóbulo Parietal/patología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Patients with schizophrenia and their first-degree relatives exhibit both abnormally diminished and increased neural activation during cognitive tasks. In particular, excessive task-related activity is often observed when tasks are easy, suggesting that inefficient cerebral recruitment may be a marker of vulnerability for schizophrenia. This hypothesis might best be tested using a very easy task, thus avoiding confounding by individual differences in task difficulty. METHOD: Eighteen people with schizophrenia, 18 unaffected full siblings of patients with schizophrenia and 26 healthy controls performed an easy auditory target-detection task in a 3-T magnetic resonance imaging (MRI) scanner. Groups were matched for accuracy on the task. Blood oxygen level-dependent (BOLD) responses to non-target stimuli in participants with vulnerability for schizophrenia (siblings and patients) were compared with those of healthy controls, and those of patients with those of unaffected siblings. BOLD responses to targets were compared with baseline, across groups. RESULTS: Subjects with vulnerability for schizophrenia showed significant hyperactivation to non-targets in brain areas activated by targets in all groups, in addition to reduced deactivation to non-targets in areas suppressed by targets in all groups. Siblings showed greater activation than patients to non-targets in the medial frontal cortex. Patients exhibited significantly longer reaction times (RTs) than unaffected siblings and healthy controls. CONCLUSIONS: Inefficient cerebral recruitment is a vulnerability marker for schizophrenia, marked by reduced suppression of brain areas normally deactivated in response to task stimuli, and increased activation of areas normally activated in response to task stimuli. Moreover, siblings show additional activation in the medial frontal cortex that may be protective.
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Corteza Cerebral/fisiopatología , Esquizofrenia/fisiopatología , Detección de Señal Psicológica/fisiología , Adulto , Percepción Auditiva/fisiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Imagen por Resonancia Magnética , Masculino , Tiempo de Reacción/fisiología , Hermanos , Adulto JovenRESUMEN
In recent years, one of the most important findings in systems neuroscience has been the identification of large scale distributed brain networks. These networks support healthy brain function and are perturbed in a number of neurological disorders (e.g. schizophrenia). Their study is therefore an important and evolving focus for neuroscience research. The majority of network studies are conducted using functional magnetic resonance imaging (fMRI) which relies on changes in blood oxygenation induced by neural activity. However recently, a small number of studies have begun to elucidate the electrical origin of fMRI networks by searching for correlations between neural oscillatory signals from spatially separate brain areas in magnetoencephalography (MEG) data. Here we advance this research area. We introduce two methodological extensions to previous independent component analysis (ICA) approaches to MEG network characterisation: 1) we show how to derive pan-spectral networks that combine independent components computed within individual frequency bands. 2) We show how to measure the temporal evolution of each network with millisecond temporal resolution. We apply our approach to ~10h of MEG data recorded in 28 experimental sessions during 3 separate cognitive tasks showing that a number of networks could be identified and were robust across time, task, subject and recording session. Further, we show that neural oscillations in those networks are modulated by memory load, and task relevance. This study furthers recent findings on electrodynamic brain networks and paves the way for future clinical studies in patients in which abnormal connectivity is thought to underlie core symptoms.
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Encéfalo/fisiología , Fenómenos Electrofisiológicos/fisiología , Red Nerviosa/fisiología , Desempeño Psicomotor/fisiología , Adulto , Algoritmos , Cognición/fisiología , Interpretación Estadística de Datos , Electroencefalografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Magnetoencefalografía , Masculino , Memoria a Corto Plazo/fisiología , Estimulación Luminosa , Análisis de Componente Principal , Percepción Visual/fisiologíaRESUMEN
Major depressive disorder (MDD) is frequently co-morbid with anxiety disorders. The co-morbid state has poorer functional outcomes and greater resistance to first line treatments, highlighting the need for novel treatment targets. This systematic review examined differences in resting-state brain connectivity associated with anxiety comorbidity in young- and middle-aged adults with MDD, with the aim of identifying novel targets for neuromodulation treatments, as these treatments are thought to work partly by altering dysfunctional connectivity pathways. Twenty-one studies met inclusion criteria, including a total of 1292 people with MDD. Only two studies included people with MDD and formally diagnosed co-morbid anxiety disorders; the remainder included people with MDD with dimensional anxiety measurement. The quality of most studies was judged as fair. Results were heterogeneous, partly due to a focus on a small set of connectivity relationships within individual studies. There was evidence for dysconnectivity between the amygdala and other brain networks in co-morbid anxiety, and an indication that abnormalities of default mode network connectivity may play an underappreciated role in this condition.
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Trastorno Depresivo Mayor , Adulto , Ansiedad , Trastornos de Ansiedad , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodos , Comorbilidad , Trastorno Depresivo Mayor/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , MorbilidadRESUMEN
BACKGROUND: An intrinsic cerebral network comprising the anterior cingulate and anterior insula (the salience network) is considered to play an important role in salience detection in healthy volunteers. Aberrant salience has been proposed as an important mechanism in the production of psychotic symptoms such as delusions and hallucinations (reality distortion). We investigated whether structural deficits in the salience network are associated with the reality distortion seen in schizophrenia. METHOD: A sample of 57 patients in a clinically stable state of schizophrenia and 41 controls were studied with high-resolution magnetic resonance imaging. RESULTS: Bilateral volume reduction was seen in the anterior cingulate and anterior insula in patients with schizophrenia. Reduced volume in the two left-sided regions of the salience network was significantly correlated with the severity of reality distortion. CONCLUSIONS: These findings suggest that a deficit of grey matter in the salience network leads to an impaired attribution of salience to stimuli that is associated with delusions and hallucinations in schizophrenia.
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Corteza Cerebral/patología , Giro del Cíngulo/patología , Esquizofrenia/patología , Psicología del Esquizofrénico , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/patología , Escalas de Valoración PsiquiátricaRESUMEN
BACKGROUND: Current classification systems do not allow for comorbid diagnoses of attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). Children with ADHD are often screened for ASD during clinical assessment and when recruited to clinical trials. We predicted that children with ADHD would have more autistic traits than controls and that certain traits would be more prevalent. METHODS: The clinically referred sample consisted of 30 children with ADHD and 30 matched controls aged 9-15 years. Children were screened for ASD traits using the Social Aptitudes Scale (SAS) and the Social Communication Questionnaire (SCQ). RESULTS: We found that ASD traits were significantly higher in children with ADHD than controls. None of the children received a diagnosis of autism or ASD. However, a large proportion (28% using the SCQ and 62% using the SAS) of children with ADHD reached screening thresholds for a predictive diagnosis of ASD. Relative to controls, children with ADHD had significantly higher levels of communication and social deficits, but not repetitive behaviours. CONCLUSION: Further work is needed to establish whether autistic-like communication and social difficulties in children with ADHD are part of the broader ASD phenotype or are specific to ADHD.
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Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno Autístico/complicaciones , Escalas de Valoración Psiquiátrica , Adolescente , Factores de Edad , Estudios de Casos y Controles , Niño , Conducta Infantil , Comorbilidad , Femenino , Humanos , Masculino , Modelos TeóricosRESUMEN
BACKGROUND: The use of symptom dimensions of schizophrenia as quantitative phenotypes has been proposed as a mean to reduce the heterogeneity of schizophrenia and facilitate genetic research. However, the genetic background of symptom dimensions is not clear. AIM: We aim to investigate whether the symptom dimensions "reality distortion", "psychomotor poverty" and "disorganization" are heritable phenotypes. METHOD: We performed a Medline search including all papers from 1980 to August 2007. In addition to reviewing the articles, we performed meta-analyses on these studies where possible. RESULTS: We identified 18 relevant papers. Only the studies on affected sibling pairs were suitable for meta-analysis. Data from twin and affected sibling studies are consistent with a genetic contribution to the disorganization dimension. However these studies did not unequivocally support a large genetic contribution to neither the reality distortion symptom dimension nor to the psychomotor poverty symptom dimension. In contrast several molecular genetic studies did report associations of genes with psychomotor poverty. CONCLUSIONS: These data suggest that only the disorganization symptom dimension may provide an useful alternative phenotype for genetic research. More research is required to make any definitive conclusions.
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Esquizofrenia/genética , Psicología del Esquizofrénico , Enfermedades en Gemelos/diagnóstico , Enfermedades en Gemelos/genética , Familia , Heterogeneidad Genética , Genotipo , Humanos , Desequilibrio de Ligamiento , Linaje , Fenotipo , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/genética , Prueba de Realidad , Esquizofrenia/diagnóstico , Esquizofrenia Hebefrénica/genéticaRESUMEN
BACKGROUND: Previous research has shown cognitive deficits in patients with schizophrenia spectrum disorders in the areas of executive function, verbal memory and attention. Subtle deficits have been shown in healthy first-degree relatives of patients, suggesting that they may be trait markers. The specificity of these markers for schizophrenia compared with another neurodevelopmental disorder, Attention Deficit Hyperactivity Disorder (ADHD) has not been reliably established. METHODS: The Rey Auditory Verbal Learning Test (RAVLT), Hayling Sentence Completion Test (HSCT), FAS Test of orthographic verbal fluency (FAS) and Continuous Performance Test-Identical Pairs (CPT-IP) were administered to adolescent schizophrenia spectrum patients (SZ; n=30), adolescent siblings of schizophrenia spectrum patients (SZ-SIB; n=36), healthy control participants (HC; n=72); a neurodevelopmental comparison group of adolescents with ADHD (n=27). RESULTS: The SZ group were impaired on all measures. The SZ-SIB group were impaired on IQ, immediate recall (RAVLT), target sensitivity (CPT-IP), response initiation (HSCT); error rates for the FAS and HSCT. There were no significant differences between the SZ-SIB and ADHD groups on individual measures of cognitive function. Principal Components Analysis revealed four factors on which further analyses were conducted. The SZ-SIB and ADHD groups showed different profiles of impairment on components related to response initiation and sustained attention/vigilance when each was compared with the HC group. CONCLUSIONS: Deficits in intellectual function, verbal memory and response initiation/inhibition were found in the SZ-SIB group indicating that these are markers of risk for schizophrenia. Subtle differences in profiles of impairment in the SZ-SIB and ADHD groups on composite measures of attention and response initiation require further investigation.
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Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/genética , Esquizofrenia/diagnóstico , Esquizofrenia/genética , Trastorno de la Personalidad Esquizotípica/diagnóstico , Trastorno de la Personalidad Esquizotípica/genética , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/psicología , Trastornos del Conocimiento/psicología , Femenino , Predisposición Genética a la Enfermedad/genética , Predisposición Genética a la Enfermedad/psicología , Humanos , Masculino , Pruebas Neuropsicológicas , Psicología del Esquizofrénico , Trastorno de la Personalidad Esquizotípica/psicología , HermanosRESUMEN
BACKGROUND: Positron emission tomography (PET) allows the measurement of benzodiazepine-gamma-aminobutyric acidA (GABA(A)) receptor kinetics. We employed flumazenil radiolabeled with carbon 11, a radioligand that labels the benzodiazepine site on the GABA(A) receptor, and fully quantitative, high-sensitivity PET to test the hypothesis that central benzodiazepine site binding is decreased in medication-free patients with panic disorder. METHODS: We compared 7 patients with panic disorder who had been off medication for at least 6 months and who had never abused alcohol with 8 healthy controls. The resulting parametric voxel-by-voxel maps were analyzed by voxel-based and region of interest-based methods using both parametric and nonparametric statistics. RESULTS: The major finding was that there is a global reduction in benzodiazepine site binding throughout the brain in patients with panic disorder compared with controls. There were sex differences in the 2 samples, but a separate analysis excluding women led to the same conclusions. In addition, the loci with the largest regional decrease in binding (right orbitofrontal cortex and right insula) were areas thought to be essential in the central mediation of anxiety. CONCLUSION: These results must be considered preliminary but are congruous with previous clinical psychopharmacologic evidence of involvement of the benzodiazepine-GABA(A) receptor and demonstrate that decreased flumazenil binding at this site may underlie panic disorder.
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Encéfalo/metabolismo , Trastorno de Pánico/diagnóstico , Receptores de GABA-A/metabolismo , Tomografía Computarizada de Emisión , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Femenino , Flumazenil , Lateralidad Funcional , Humanos , Masculino , Persona de Mediana Edad , Trastorno de Pánico/diagnóstico por imagen , Trastorno de Pánico/fisiopatología , Inventario de Personalidad , Factores Sexuales , Distribución Tisular , Ácido gamma-Aminobutírico/fisiologíaRESUMEN
BACKGROUND: Postmortem and brain imaging studies that measured brain serotinin(2) (5-HT(2)) receptors in major depression reported an increase, decrease, and no change compared with controls. In this study, we assessed brain 5-HT(2) receptors in 20 depressed patients (mean +/- SD age, 40.1 +/- 9.5 years; range, 22-60 years) and 20 healthy controls similar in age (37.2 +/- 12.6 years; range, 19-59 years) using positron emission tomography and setoperone labeled with fluorine 18 ([(18)F]setoperone). METHODS: Patients with DSM-IV major depression and healthy controls underwent scanning with [(18)F]setoperone. All study subjects were drug free for at least 2 weeks. The 5-HT(2) binding images were created using region-to-cerebellum ratios. The differences in 5-HT(2) receptor binding potential between the two groups were determined with statistical parametric mapping software and region of interest analysis. RESULTS: There was a significant negative correlation between 5-HT(2) receptor binding potential and age in both patients and controls, and the magnitude of this correlation was similar in both groups. Both statistical parametric mapping and region of interest analyses showed that, compared with healthy controls, depressed patients had significantly lower 5-HT(2) receptor binding potential in frontal, temporal, parietal, and occipital cortical regions. Statistical parametric mapping analysis showed that the mean decrease in 5-HT(2) receptor binding potential for the entire cluster in these regions was 22%, and it ranged from 22% to 27% for local maxima within the clusters of significant voxels. CONCLUSION: This study suggests that brain 5-HT(2) receptors are decreased in patients with major depression.
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Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/metabolismo , Receptores de Serotonina/metabolismo , Tomografía Computarizada de Emisión/estadística & datos numéricos , Adulto , Factores de Edad , Cerebelo/química , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Femenino , Radioisótopos de Flúor , Lóbulo Frontal/química , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Lóbulo Occipital/química , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/metabolismo , Lóbulo Parietal/química , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/metabolismo , Pirimidinonas , Receptores de Serotonina/análisis , Factores Sexuales , Lóbulo Temporal/química , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/metabolismoRESUMEN
BACKGROUND: Formal thought disorder (FTD) is a core symptom of schizophrenia, but its pathophysiology is little understood. We examined the neural correlates of FTD using functional magnetic resonance imaging. METHODS: Blood oxygenation level-dependent contrast was measured using functional magnetic resonance imaging while 6 patients with schizophrenia and 6 control subjects spoke about 7 Rorschach inkblots for 3 minutes each. In patients, varying degrees of thought-disordered speech were elicited during each "run." In a within-subject design, the severity of positive FTD was correlated with the level of blood oxygenation level-dependent contrast in the 2 runs that showed the highest variance of FTD in each patient. RESULTS: The severity of positive FTD in patients was negatively correlated (P<.001) with signal changes in the left superior and middle temporal gyri. Positive correlations were evident in the cerebellar vermis, the right caudate body, and the precentral gyrus. CONCLUSIONS: The severity of positive FTD was inversely correlated with the level of activity in the Wernicke area, a region implicated in the production of coherent speech. Reduced activity in this area might contribute to the articulation of incoherent speech. Because of the small sample size, these findings should be considered preliminary.
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Encéfalo/fisiología , Imagen por Resonancia Magnética/estadística & datos numéricos , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Habla/fisiología , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Núcleo Caudado/irrigación sanguínea , Núcleo Caudado/fisiología , Cerebelo/irrigación sanguínea , Cerebelo/fisiología , Humanos , Masculino , Oxígeno/sangre , Flujo Sanguíneo Regional , Prueba de Rorschach , Esquizofrenia/fisiopatología , Índice de Severidad de la Enfermedad , Lóbulo Temporal/irrigación sanguínea , Lóbulo Temporal/fisiologíaRESUMEN
BACKGROUND: The neuroreceptor changes involved in therapeutic efficacy of various antidepressants remain unclear. Preclinical studies have shown that long-term administration of various antidepressants causes down-regulation of brain serotonin 2 (5-HT2) receptors in rodents, but it is unknown if similar changes occur following antidepressant treatment in depressed patients. Our purpose, therefore, was to assess the effects of treatment with desipramine hydrochloride on brain 5-HT2 receptors in depressed patients using positron emission tomography (PET) and fluorine-18 (18F)-labeled setoperone. METHODS: Eleven patients who met DSM-IV criteria for major depression as determined by a structured clinical interview for DSM-III-R diagnosis and suitable for treatment with desipramine were recruited. Ten patients underwent a PET scan before and another after 3 to 4 weeks of treatment with desipramine. RESULTS: Eight of the 10 patients responded to desipramine treatment as indicated by more than 50% decrease in Hamilton Depression Rating Scale scores. Depressed patients showed a significant decrease in 5-HT2 receptor binding as measured by setoperone binding in frontal, temporal, parietal, and occipital cortical regions following desipramine treatment. The decrease in 5-HT2 receptor binding was observed bilaterally and was particularly prominent in frontal cortex. CONCLUSIONS: Depressed patients showed a significant reduction in available 5-HT2 receptors in the brain following desipramine treatment, but it is unknown if this change in 5-HT2 receptors is due to clinical improvement or an effect of desipramine that is unrelated to clinical status.
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Antidepresivos Tricíclicos/uso terapéutico , Encéfalo/diagnóstico por imagen , Trastorno Depresivo/tratamiento farmacológico , Desipramina/uso terapéutico , Receptores de Serotonina/metabolismo , Tomografía Computarizada de Emisión , Antidepresivos Tricíclicos/farmacología , Encéfalo/metabolismo , Trastorno Depresivo/metabolismo , Desipramina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Radioisótopos de Flúor , Fluorodesoxiglucosa F18 , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/metabolismo , Humanos , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/metabolismo , Pirimidinonas , Receptores de Serotonina/efectos de los fármacosRESUMEN
BACKGROUND: Clinicians have long recognized that psychopaths show deficits in cognitive function, but there have been few experimental studies exploring these deficits. We present here the first in a series of event-related potential (ERP) experiments designed to elucidate and characterize the neural correlates of cognitive processes of psychopaths. METHODS: We recorded ERPs from a topographic array from 11 psychopathic and 10 nonpsychopathic prison inmates, assessed with the Hare Psychopathy Checklist-Revised, during performance of a visual oddball task. ERPs to target (25% of trials) and nontarget (75% of trials) visual stimuli were analyzed. RESULTS: Consistent with previous research, there were no group differences in the latency or amplitude of the ERPs for the nontarget stimuli. For nonpsychopaths, the P300 amplitude was larger when elicited by the target stimuli than when elicited by the nontarget stimuli. In contrast, psychopaths failed to show reliable P300 amplitude differences between the target and nontarget conditions. Psychopaths had a smaller amplitude P300 to target stimuli than did nonpsychopaths. In addition, the amplitude of the P300 was less lateralized in psychopaths than in nonpsychopaths. Psychopaths also had a larger centrofrontal negative wave (N550) during the target condition than did nonpsychopaths. CONCLUSIONS: The results of this study indicate that there are substantial differences between psychopaths and others in the processing of even simple cognitive tasks and provide support for information processing models of psychopathy.
Asunto(s)
Trastorno de Personalidad Antisocial , Atención/fisiología , Corteza Cerebral/fisiopatología , Trastornos del Conocimiento , Potenciales Relacionados con Evento P300/fisiología , Volición/fisiología , Adulto , Análisis de Varianza , Trastorno de Personalidad Antisocial/complicaciones , Trastorno de Personalidad Antisocial/fisiopatología , Estudios de Casos y Controles , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/fisiopatología , Señales (Psicología) , Discriminación en Psicología/fisiología , Humanos , Inhibición Psicológica , Masculino , Persona de Mediana Edad , Inhibición Neural/fisiología , Prisioneros , Percepción del Tamaño/fisiologíaRESUMEN
BACKGROUND: Schizophrenia and psychopathy are both characterized by impulsive, poorly planned behavior. This behavior may originate from a weak or poorly coordinated response inhibition system. We tested the hypothesis that schizophrenia and psychopathy are associated with abnormal neural processing during the suppression of inappropriate responses. METHODS: The participants were schizophrenic patients, nonpsychotic psychopaths, and nonpsychotic, nonpsychopathic control subjects (defined by the Hare Psychopathy Checklist-Revised), all incarcerated in a maximum security psychiatric facility. We recorded behavioral responses and event-related potentials (ERPs) during a Go/No Go task. RESULTS: Schizophrenic patients made more errors of commission than did the nonpsychopathic offenders. As expected, the nonpsychopathic nonpsychotic participants showed greater frontal ERP negativity (N275) to the No Go stimuli than to the Go stimuli. This effect was small in the schizophrenic patients and absent in the psychopaths. For the nonpsychopaths, the P375 ERP component was larger on Go than on No Go trials, a difference that was absent in schizophrenic patients and in the opposite direction in psychopaths. CONCLUSIONS: These findings support the hypothesis that the neural processes involved in response inhibition are abnormal in both schizophrenia and psychopathy; however, the nature of these processes appears to be different in the two disorders.