RESUMEN
The neuronal underpinnings of cortical folding alterations in schizophrenia remain unclear. Theories on the physiological development of cortical folds stress the importance of white matter fibers for this process and disturbances of fiber tracts might be relevant for cortical folding alterations in schizophrenia. Nine-teen patients with schizophrenia and 19 healthy subjects underwent T1-weighted MRI and DTI. Cortical folding was computed using a surface based approach. DTI was analyzed using FSL and SPM 5. Radial diffusivity and cortical folding were correlated covering the entire cortex in schizophrenia. Significantly increased radial diffusivity of the superior longitudinal fasciculus (SLF) in the left superior temporal region was negatively correlated with cortical folding of the left dorsolateral prefrontal cortex (DLPFC) in patients, i.e. higher radial diffusivity, as an indicator for disturbed white matter fiber myelination, was associated with lower cortical folding of the left DLPFC. Patients with pronounced alterations of the SLF showed significantly reduced cortical folding in the left DLPFC. Our study provides novel evidence for a linkage between prefrontal cortical folding alterations and deficits in connecting white matter fiber tracts in schizophrenia and supports the notion that the integrity of white matter tracts is crucial for intact morphogenesis of the cortical folds.
Asunto(s)
Red Nerviosa/diagnóstico por imagen , Corteza Prefrontal/diagnóstico por imagen , Esquizofrenia/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Alterations in the dopaminergic reward system, predominantly the striatum, constitute core characteristics of schizophrenia. AIMS: Functional connectivity of the dorsal striatum during reward-related trial-and-error learning was investigated in 17 people with schizophrenia and 18 healthy volunteers and related to striatal grey matter volume and psychopathology. METHOD: We used voxel-based morphometry and psychophysiological interaction to examine striatal volume and connectivity. RESULTS: A reduced functional connectivity between left striatum and temporo-occipital areas, precuneus and insula could be detected in the schizophrenia group. The positive correlation between grey matter volume and functional connectivity of the left striatum yielded significant results in a very similar network. Connectivity of the left striatum was negatively correlated with negative symptoms. CONCLUSIONS: Present results suggest a disruption in striatal functional connectivity that is closely linked to grey matter morphometry of the striatum. Decreased connectivity between the striatum and psychopathologically relevant networks may explain the emergence of negative symptoms.
Asunto(s)
Cuerpo Estriado/patología , Sustancia Gris/patología , Red Nerviosa/patología , Esquizofrenia/patología , Adulto , Mapeo Encefálico , Cuerpo Estriado/fisiopatología , Femenino , Sustancia Gris/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/fisiopatología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Esquizofrenia/fisiopatologíaRESUMEN
Individual responsiveness to rewards or rewarding stimuli may affect various domains of normal as well as pathological behavior. The ventral striatum/nucleus accumbens (NAcc) constitutes a key brain structure in the regulation of reward-appetitive behavior. It remains unclear, however, to which extent individual reward-related BOLD response in the NAcc is dependent on individual characteristics of connecting white matter fiber tracts. Using tract-based spatial statistics (TBSS) and statistical parametric mapping (SPM) this combined DTI - fMRI study investigated this question by correlating NAcc BOLD signal upon receipt of a monetary reward with different white matter characteristics (FA, axial diffusivity, radial diffusivity). The results show that increased integrity of white matter as assessed by FA in the cingulate and corpus callosum, the inferior fronto-occipital fasciculus, the anterior thalamic radiation and the anterior limb of the internal capsule was positively correlated with reward-related activation in the NAcc. There were no negative correlations as well as no significant results regarding axial and radial diffusivity. These findings indicate that microstructural properties of fiber tracts connecting, amongst others, the cortex with the striatum may influence intensity of reward-related responsiveness of the ventral striatum by constraining or increasing efficiency in information transfer within relevant circuitries involved in processing of reward.
Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Fibras Nerviosas Mielínicas , Recompensa , Estriado Ventral/fisiología , Adulto , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Fibras Nerviosas Mielínicas/fisiología , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Pruebas Neuropsicológicas , Oxígeno/sangre , Probabilidad , Estriado Ventral/anatomía & histologíaRESUMEN
Recent evidence indicated that the ZNF804A (rs1344706) risk allele A is associated with better cognitive performance in patients with schizophrenia. Moreover, it has been demonstrated that ZNF804A may also be related to relatively intact gray matter volume in patients. To further explore these putatively protective effects, the impact of ZNF804A on cortical thickness and folding was examined in this study. To elucidate potential molecular mechanisms, an allelic-specific gene expression study was also carried out. Magnetic resonance imaging cortical thickness and folding were computed in 55 genotyped patients with schizophrenia and 40 healthy controls. Homozygous risk allele carriers (AA) were compared with AC/CC carriers. ZNF804A gene expression was analyzed in a prefrontal region using postmortem tissue from another cohort of 35 patients. In patients, AA carriers exhibited significantly thicker cortex in prefrontal and temporal regions and less disturbed superior temporal cortical folding, whereas the opposite effect was observed in controls, ie, AA carrier status was associated with thinner cortex and more severe altered cortical folding. Along with this, our expression analysis revealed that the risk allele is associated with lower prefrontal ZNF804A expression in patients, whereas the opposite effect in controls has been observed by prior analyses. In conclusion, our analyses provide convergent support for the hypothesis that the schizophrenia-associated ZNF804A variant mediates protective effects on cortex structure in patients. In particular, the allele-specific expression profile in patients might constitute a molecular mechanism for the observed protective influence of ZNF804A on cortical thickness and folding and potentially other intermediate phenotypes.
Asunto(s)
Trastornos del Conocimiento/patología , Sustancia Gris/patología , Factores de Transcripción de Tipo Kruppel/genética , Corteza Prefrontal/patología , Esquizofrenia/patología , Adolescente , Adulto , Estudios de Casos y Controles , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Trastornos del Conocimiento/genética , Femenino , Perfilación de la Expresión Génica , Sustancia Gris/metabolismo , Heterocigoto , Homocigoto , Humanos , Factores de Transcripción de Tipo Kruppel/metabolismo , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Corteza Prefrontal/metabolismo , Factores Protectores , Esquizofrenia/genética , Adulto JovenRESUMEN
Probabilistic independent component analysis was applied to identify the default mode network (DMN) in resting state data obtained with functional magnetic resonance imaging from 25 DSM-IV schizophrenia and 25 matched healthy subjects. Power spectrum analysis showed a significant diagnosis × frequency interaction and higher power in one frequency band, indicating an alteration of DMN frequency spectrum in schizophrenia.
Asunto(s)
Encéfalo/fisiopatología , Red Nerviosa/fisiopatología , Esquizofrenia/fisiopatología , Adulto , Corteza Cerebral , Femenino , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
In light of bottom-up models of disrupted cognition in schizophrenia, visual processing deficits became a key feature for the pathophysiology of schizophrenia. However, morphometric studies focusing on the visual cortex are limited. Thus, the present study sought to provide a combined cortical shape analysis (cortical thickness, folding) of visual areas, which were implicated to be involved in disturbed visual processing in schizophrenia. A group of 72 patients with schizophrenia according to DSM-IV and 72 age- and gender-matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5-T scanner. Cortical thickness and mean curvature of the V1, V2 and V5/MT+ visual cortex were estimated using an automated computerized algorithm (Freesurfer Software). A GLM controlling for the effect of age was used to estimate differences of cortical shape parameters between the study groups. Significantly increased gyrification of the V1, V2 and the V5/MT+ visual area bilaterally was detected. Conversely, cortical thickness was reduced in patients with schizophrenia only for the V5/MT+ area. This study is the first providing direct in vivo evidence for a disturbed cortical shape of central visual areas in schizophrenia. The present findings of hypergyria are highly indicative for a disrupted corticogenesis of these visual key regions and might constitute a relevant anatomical basis for visual processing deficits in schizophrenia.
Asunto(s)
Esquizofrenia/patología , Corteza Visual/patología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Escalas de Valoración Psiquiátrica , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Corteza Visual/fisiopatología , Percepción Visual , Adulto JovenRESUMEN
INTRODUCTION: Both impaired white matter connectivity and alterations in gray matter morphometry have repeatedly been reported in schizophrenia. Neurodevelopmental models propose a close linkage between gray matter alterations and white matter deficits. However, there are no studies investigating alterations in cortical thickness in relation to white matter connectivity changes. METHODS: This combined diffusion tensor imaging (DTI) - surface based morphometry study examined a potential linkage between disruption in white matter connectivity and alterations in cortical thickness. Cortical thickness was analyzed using the FreeSurfer software package (version 4.0.5, http://surfer.nmr.harvard.edu) in a sample of 19 patients with schizophrenia and 20 healthy controls. RESULTS: Whole brain node-by-node correlational analysis revealed a highly significant association ( r= -.8, p < .0001) between disturbed white matter connectivity in the superior temporal cortex and diminished cortical thickness in the posterior part of the cingulate cortex (Brodmann area 23/31). CONCLUSIONS: This result indicates a significant linkage between disturbed white matter connectivity and reduced cortical thickness in a relevant node of the default mode network that is held to be of high pathophysiological relevance in schizophrenia. The result moreover provides support for the assumption of a neurodevelopmental pathogenesis of the disorder.
Asunto(s)
Giro del Cíngulo/patología , Fibras Nerviosas Mielínicas/patología , Red Nerviosa/patología , Esquizofrenia/patología , Adulto , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Giro del Cíngulo/fisiopatología , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana Edad , Esquizofrenia/fisiopatologíaRESUMEN
The Trail Making Test (TMT), which assesses motor performance, selective attention, working memory and cognitive flexibility is highly sensitive to age-related performance differences. However, the structural basis of this age-performance association is largely unknown. This DTI study examined the influence of white matter characteristics on the association between TMT performance (i.e., speed of processing) and age in a sample of 86 healthy, middle-aged subjects (mean age 27.9 years, range 18-55). Voxel-wise correlation yielded a significant negative association between FA in the body of the corpus callosum (CC) and TMT-A performance (i.e., time taken to complete the test). There was also a significant association between age and TMT-A performance. However, this association between age and TMT-A performance was neither mediated nor moderated by FA in the CC. Results suggest that fast motor performance is strongly dependent on individual white matter characteristics of the CC. This indicates that interindividual variations in white matter of the CC known to be relevant for interhemispheric motor signal transduction critically influence speed of motor processing. However, these interindividual variations do not explain the observed association between age and TMT performance.
Asunto(s)
Imagen de Difusión Tensora/métodos , Fibras Nerviosas Mielínicas/fisiología , Desempeño Psicomotor/fisiología , Prueba de Secuencia Alfanumérica , Adulto , Factores de Edad , Anisotropía , Cuerpo Calloso/fisiología , Humanos , Persona de Mediana EdadRESUMEN
Common genetic variation in the promoter region of the glutamate receptor delta 1 (GRID1) gene has recently been shown to confer increased risk for schizophrenia in several independent large samples. We analysed high-resolution magnetic resonance imaging (MRI) data from 62 patients with schizophrenia and 54 healthy controls using voxel-based morphometry (VBM) to assess the effect of single nucleotide polymorphism rs3814614 (located in the GRID1 promoter region), of which the T allele was identified as a risk factor in a previous association study. There were no effects of genotype or group × genotype interactions on total brain grey matter or white matter, but on regional grey matter. In healthy subjects, we identified a significant effect of rs3814614 genotype in the anterior thalamus (bilaterally), superior prefrontal cortex, and orbitofrontal cortex - in all cases with the homozygous risk genotype TT resulting in higher grey matter density. We did not find this association within the schizophrenia sample, where rs3814614 variation was only associated with grey matter reduction in TT homozygous subjects in medial parietal cortex and increased grey matter in right medial cerebellum. For white matter, we did not find significant genotype effects in healthy controls, and only minor effects within schizophrenia patients in the posterior temporal lobe white matter. Our data indicate that GRID1 rs3814614 genotype is related to grey matter variation in prefrontal and anterior thalamic brain areas in healthy subjects, but not in patients indicating a potential role of this schizophrenia candidate gene in thalamo-cortical functioning.
Asunto(s)
Corteza Prefrontal , Receptores de Glutamato/genética , Esquizofrenia , Tálamo , Adolescente , Adulto , Femenino , Variación Genética , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Esquizofrenia/genética , Esquizofrenia/metabolismo , Esquizofrenia/patología , Tálamo/metabolismo , Tálamo/patología , Adulto JovenRESUMEN
Substantial pathophysiological questions about the relationship of brain pathologies in psychosis can only be answered by multimodal neuroimaging approaches combining different imaging modalities such as structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET) and magnetic-resonance spectroscopy. In particular, the multimodal imaging approach has the potential to shed light on the neuronal mechanisms underlying the major brain structural and functional pathophysiological features of schizophrenia and high-risk states such as prefronto-temporal gray matter reduction, altered higher-order cognitive processing, or disturbed dopaminergic and glutamatergic neurotransmission. In recent years, valuable new findings have been revealed in these fields by multimodal imaging studies mostly reflecting a direct and aligned correlation of brain pathologies in psychosis. However, the amount of multimodal studies is still limited, and further efforts have to be made to consolidate previous findings and to extend the scope to other pathophysiological parameters contributing to the pathogenesis of psychosis. Here, investigating the genetic foundations of brain pathology relationships is a major challenge for future multimodal imaging applications in psychosis research.
Asunto(s)
Investigación Biomédica , Encéfalo , Neuroimagen/métodos , Trastornos Psicóticos , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Mapeo Encefálico , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/fisiopatología , Humanos , Imagenología Tridimensional , Metaanálisis como Asunto , Trastornos Psicóticos/diagnóstico , Trastornos Psicóticos/metabolismo , Trastornos Psicóticos/fisiopatología , CintigrafíaRESUMEN
Alterations in brain function in schizophrenia and other neuropsychiatric disorders are evident not only during specific cognitive challenges, but also from functional MRI data obtained during a resting state. Here we apply probabilistic independent component analysis (pICA) to resting state fMRI series in 25 schizophrenia patients and 25 matched healthy controls. We use an automated algorithm to extract the ICA component representing the default mode network (DMN) as defined by a DMN-specific set of 14 brain regions, resulting in z-scores for each voxel of the (whole-brain) statistical map. While goodness of fit was found to be similar between the groups, the region of interest (ROI) as well as voxel-wise analysis of the DMN showed significant differences between groups. Healthy controls revealed stronger effects of pICA-derived connectivity measures in right and left dorsolateral prefrontal cortices, bilateral medial frontal cortex, left precuneus and left posterior lateral parietal cortex, while stronger effects in schizophrenia patients were found in the right amygdala, left orbitofrontal cortex, right anterior cingulate and bilateral inferior temporal cortices. In patients, we also found an inverse correlation of negative symptoms with right anterior prefrontal cortex activity at rest and negative symptoms. These findings suggest that aberrant default mode network connectivity contributes to regional functional pathology in schizophrenia and bears significance for core symptoms.
Asunto(s)
Amígdala del Cerebelo/fisiopatología , Lóbulo Frontal/fisiopatología , Giro del Cíngulo/fisiopatología , Modelos Estadísticos , Lóbulo Parietal/fisiopatología , Esquizofrenia/fisiopatología , Lóbulo Temporal/fisiopatología , Adulto , Amígdala del Cerebelo/patología , Mapeo Encefálico , Estudios de Casos y Controles , Femenino , Lóbulo Frontal/patología , Neuroimagen Funcional , Giro del Cíngulo/patología , Humanos , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/patología , Vías Nerviosas/fisiopatología , Lóbulo Parietal/patología , Esquizofrenia/patología , Lóbulo Temporal/patologíaRESUMEN
A recent study found genome-wide significant association between common variation in the gene neurocan (NCAN, rs1064395) and bipolar disorder (BD). In view of accumulating evidence that BD and schizophrenia partly share genetic risk factors, we tested this single-nucleotide polymorphism for association with schizophrenia in three independent patient-control samples of European ancestry, totaling 5061 patients and 9655 controls. The rs1064395 A-allele, which confers risk for BD, was significantly over-represented in schizophrenia patients compared to controls (p=2.28×10(-3); odds ratio=1.11). Follow-up in non-overlapping samples from the Schizophrenia Psychiatric GWAS Consortium (5537 patients, 8043 controls) provided further support for our finding (p=0.0239, odds ratio=1.07). Our data suggest that genetic variation in NCAN is a common risk factor for BD and schizophrenia.
Asunto(s)
Proteoglicanos Tipo Condroitín Sulfato/genética , Predisposición Genética a la Enfermedad , Lectinas Tipo C/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple , Esquizofrenia/genética , Trastorno Bipolar/genética , Estudios de Casos y Controles , Frecuencia de los Genes , Genotipo , Humanos , NeurocanoRESUMEN
BACKGROUND: The anterior cingulate cortex plays a central role in altered processes of cognitive control in schizophrenia. However, the cortical foundations of disturbed anterior cingulate cognitive activation are poorly understood. Therefore, this study investigated the association of anterior cingulate cognitive activation and cortical thickness in schizophrenia combining functional magnetic resonance imaging (fMRI) and surface-based morphometry. METHODS: Fifty-three patients with schizophrenia according to DSM-IV and 53 age- and sex-matched healthy subjects were included and underwent fMRI and high-resolution T1-weighted MRI. fMRI data was analyzed using SPM5. Cortical thickness was calculated using an automated computerized algorithm (Freesurfer Software). Statistical cortical maps were created correlating anterior cingulate activation and cortical thickness on a node-by-node basis covering the entire cortex in schizophrenia and healthy control subjects. RESULTS: Patients demonstrated a significantly reduced anterior cingulate cognitive activation. Significantly differing associations of anterior cingulate activation and cortical thickness were found in a pattern of dorsolateral prefrontal, superior frontal-anterior cingulate, and superior temporal cortical regions, where patients but not healthy control subjects demonstrated a significant association of reduced anterior cingulate activation and cortical thinning. A direct comparison of cortical thickness between the diagnostic groups revealed a significantly reduced cortical thickness of these prefrontotemporal regions in schizophrenia. CONCLUSIONS: To our best knowledge, this is the first study indicating that prefrontotemporal cortical thinning constitutes a relevant cortical pathomechanism for altered cognitive activation in schizophrenia. Our data additionally reveal a profound disruption of structural and functional integration in the prefrontotemporal system in schizophrenia.
Asunto(s)
Cognición/fisiología , Giro del Cíngulo/fisiopatología , Corteza Prefrontal/patología , Esquizofrenia/patología , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Lóbulo Temporal/patología , Adolescente , Adulto , Atrofia/patología , Atrofia/psicología , Mapeo Encefálico/métodos , Mapeo Encefálico/psicología , Mapeo Encefálico/estadística & datos numéricos , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Magnética/psicología , Imagen por Resonancia Magnética/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Desempeño Psicomotor/fisiología , Lóbulo Temporal/fisiopatologíaRESUMEN
Psychoeducation has proved to be an effective treatment method for the prevention of relapse in recurrent depression. However, little is known about the processes which could account for the effects of psychoeducational treatment. In this study, patients with recurrent depression (currently remitted) received, over a period of 8 months, 16 sessions of psychoeducational treatment, in order to prevent relapse. Therapist adherence and competence, and the therapeutic alliance, were investigated as predictors of reducing the recurrence risk in depression. Videotapes of 43 participants in a psychoeducational treatment for depression were analyzed, in order to evaluate therapist adherence and competence. Additionally, the therapeutic alliance was assessed by means of a questionnaire. One year after treatment, no associations were found between therapist adherence or competence and the risk of relapse. The patients' view of the therapeutic alliance was moderately associated with the time to relapse. However, the correlation disappeared when controlled for the number of previous depressive episodes. The latter was the most important predictor of time to relapse, explaining 15% of variance.
Asunto(s)
Competencia Clínica , Depresión/psicología , Depresión/rehabilitación , Cooperación del Paciente , Psicoterapia/métodos , Adulto , Anciano , Análisis de Varianza , Depresión/prevención & control , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Prevención Secundaria , Resultado del TratamientoRESUMEN
There is evidence that the different symptom dimensions in obsessive-compulsive disorder (OCD) may be mediated by partially distinct neural systems. This DTI study investigated the relationship between symptom dimensions and white matter microstructure. Fractional anisotropy (FA), axial and radial diffusivity was analyzed in relation to the main OCD symptom dimensions. Symptom severity on the obsessing dimension was negatively correlated with FA in the corpus callosum and the cingulate bundle. Severity on the ordering dimension was negatively correlated with FA in, amongst others, the right inferior fronto-occipital fasciculus and the right optic radiation. All correlations were ascribable to alterations in radial diffusivity while there was no association between symptoms and axial diffusivity. Present results illustrate an association between alterations in visual processing tracts and ordering symptoms which are characterized by altered visual processing and increased attention towards irrelevant detail. They also indicate an association between obsessive thoughts and alterations in structures known to be relevant for cognitive control and inhibition. Hence, different symptom dimensions must be taken into account in order to disentangle the neurobiological underpinnings of OCD.
Asunto(s)
Mapeo Encefálico , Encéfalo/patología , Fibras Nerviosas Mielínicas/patología , Trastorno Obsesivo Compulsivo/patología , Trastorno Obsesivo Compulsivo/fisiopatología , Adulto , Anisotropía , Encéfalo/efectos de los fármacos , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Procesamiento de Imagen Asistido por Computador , Masculino , Fibras Nerviosas Mielínicas/efectos de los fármacos , Trastorno Obsesivo Compulsivo/tratamiento farmacológico , Escalas de Valoración Psiquiátrica , Adulto JovenRESUMEN
In light of current etiological concepts the glutamatergic system plays an essential role for the pathophysiology of the disorder, offering multiple options for new treatment strategies. The D-amino oxidase activator (DAOA) gene is closely connected to the glutamatergic system and its therapeutic and pathophysiological relevance for schizophrenia is therefore intensively debated. In a further step to shed light on the role of DAOA in schizophrenia, we aimed to investigate the association of the functional DAOA Arg30Lys (rs2391191) variant and cortical thickness in schizophrenia. Cortical thickness was computed by an automated surface-based technique (FreeSurfer) in 52 genotyped patients with schizophrenia and 42 healthy controls. Cortical thickness of the entire cortex was compared between risk carriers and non-risk carriers regarding the Arg30Lys polymorphism in patients and healthy controls on the basis of a node-by-node procedure and an automated clustering approach. Risk carriers with schizophrenia show significantly thinner cortex in two almost inversely arranged clusters on the left and right hemisphere comprising middle temporal, inferior parietal, and lateral occipital cortical areas. The clusters encompass an area of 1174 mm(2) (left) and 1156 mm(2) (right). No significant effect was observed in healthy controls.The finding of our study that the Arg30Lys risk variant is associated with a distinct cortical thinning provides new evidence for the pathophysiological impact of DAOA in schizophrenia. The affected areas are mostly confined to cortical regions with a crucial role in the ToM network and visual processing, which both can be influenced by glutamatergic modulation. Our finding thus underlines the importance of DAOA and related glutamatergic processes as a putative target for therapeutic interventions in schizophrenia.
Asunto(s)
Proteínas Portadoras/genética , Corteza Cerebral/patología , Predisposición Genética a la Enfermedad/genética , Variación Genética/genética , Ácido Glutámico/fisiología , Esquizofrenia/genética , Esquizofrenia/patología , Adulto , Arginina/genética , Femenino , Estudios de Asociación Genética/métodos , Humanos , Péptidos y Proteínas de Señalización Intracelular , Lisina/genética , Masculino , Polimorfismo Genético/genética , Adulto JovenRESUMEN
BACKGROUND: Schizophrenia is associated with often widespread changes in white matter structure. Most studies have investigated changes in fractional anisotropy, whereas alterations in radial or axial diffusivity have barely been investigated until now. AIMS: To investigate radial diffusivity as a potential marker of dysmyelination in direct relation to abnormalities in neural activation. METHOD: Neural activation in association with decision-making under uncertainty was investigated in 19 people with schizophrenia and 20 healthy controls and linked to radial diffusivity as measured by diffusion tensor imaging. RESULTS: Decision-making under uncertainty was associated with a significantly decreased activation in a frontostriatocingulate network in the schizophrenia group. Structurally, they exhibited increased radial diffusivity in temporal white matter that was negatively correlated with activation in parts of the frontostriatocingulate network. CONCLUSIONS: Present data indicate that altered diffusivity within relevant white matter networks may be closely linked to abnormal neural activation in schizophrenia.
Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/patología , Imagen de Difusión Tensora/métodos , Imagen por Resonancia Magnética/métodos , Esquizofrenia/patología , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Toma de Decisiones , Difusión , Femenino , Lateralidad Funcional , Humanos , Masculino , Vías Nerviosas/patología , IncertidumbreRESUMEN
Studies using diffusion tensor imaging (DTI) have shown multifocal reduction in anisotropy of white matter fibre tracts in schizophrenia, and a few of these also suggest changes in apparent diffusion coefficient (ADC). In this study, we assessed ADC in 18 patients with schizophrenia and 18 healthy controls using a voxel-based approach. We did not find evidence of statistically significant changes in ADC in either direction at P < 0.05 (FDR corrected) using different smoothing filter sizes; only at an uncorrected threshold of P < 0.001 did we find an increase in a small right prefrontal area close to our previous FA finding. Our findings therefore do not support ADC changes to be a marker of white matter or grey matter abnormalities in schizophrenia. Changes in other parameters like fractional anisotropy (FA) might be a more sensitive indicator of white matter pathology in this disorder.
Asunto(s)
Mapeo Encefálico , Encéfalo/patología , Imagen de Difusión Tensora/métodos , Esquizofrenia/patología , Adulto , Anisotropía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Adulto JovenRESUMEN
The formation of new perceptual categories involves learning to extract that information from a wide range of often noisy sensory inputs, which is critical for selecting between a limited number of responses. To identify brain regions involved in visual classification learning under noisy conditions, we developed a task on the basis of the classical dot pattern prototype distortion task [M. I. Posner, Journal of Experimental Psychology, 68, 113-118, 1964]. Twenty-seven healthy young adults were required to assign distorted patterns of dots into one of two categories, each defined by its prototype. Categorization uncertainty was modulated parametrically by means of Shannon's entropy formula and set to the levels of 3, 7, and 8.5 bits/dot within subsets of the stimuli. Feedback was presented after each trial, and two parallel versions of the task were developed to contrast practiced and unpracticed performance within a single session. Using event-related fMRI, areas showing increasing activation with categorization uncertainty and decreasing activation with training were identified. Both networks largely overlapped and included areas involved in visuospatial processing (inferior temporal and posterior parietal areas), areas involved in cognitive processes requiring a high amount of cognitive control (posterior medial wall), and a cortico-striatal-thalamic loop through the body of the caudate nucleus. Activity in the medial prefrontal wall was increased when subjects received negative as compared with positive feedback, providing further evidence for its important role in mediating the error signal. This study characterizes the cortico-striatal network underlying the classification of distorted visual patterns that is directly related to decision uncertainty.
Asunto(s)
Conducta de Elección/fisiología , Aprendizaje/fisiología , Modelos Neurológicos , Distorsión de la Percepción/fisiología , Incertidumbre , Percepción Visual/fisiología , Adulto , Entropía , Retroalimentación , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Procesos Mentales/fisiología , Estimulación Luminosa/métodos , Adulto JovenRESUMEN
OBJECTIVE: Cerebral gyrification is attributed to a large extent to genetic and intrauterine/perinatal factors. Hence, investigating gyrification might offer important evidence for disturbed neurodevelopmental mechanisms in schizophrenia. As an extension of recent ROI analyses of gyrification in schizophrenia the present study is the first to compare on a node-by-node basis mean curvature as a sensitive parameter for the identification of local gyrification changes of the whole cortex in first-episode schizophrenia. METHODS: A group of 54 patients with first-episode schizophrenia according to DSM-IV and 54 age and gender matched healthy control subjects were included. All participants underwent high-resolution T1-weighted MRI scans on a 1.5 T scanner. Mean curvature was calculated dividing the sum of the principal curvatures by two at each point of the curved surface as implemented in the Freesurfer Software package. Statistical cortical maps were created to estimate gyrification differences between groups based on a clustering approach. RESULTS: A significantly increased gyrification was observed in first-episode schizophrenia patients relative to controls in a right parahippocampal-lingual cortex area. The cluster encompassed a surface area of 750 mm². A further analysis of cortical thickness of this cluster demonstrated concurrent significant reduced cortical thickness of this area. CONCLUSIONS: This is the first study to reveal an aberrant gyrification of the medial surface in first-episode schizophrenia. This finding is in line with substantial evidence showing medial temporal lobe abnormalities in schizophrenia. The present morphometric data provide further support for an early disruption of cortical maturation in schizophrenia.