Structural neural networks subserving oculomotor function in first-episode schizophrenia

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia

Hippocampal volumes in patients with bipolar-schizophrenic spectrum disorders and their unaffected first-degree relatives

BACKGROUND: schizophrenic and bipolar disorders are complex and disabling psychiatric diseases whose classical nosography and classification are still under challenging debate aiming to overcome the traditional “Kraepelinian Dichotomy”. For the past hundred years most clinical work and research in psychiatry has proceeded under the assumption that schizophrenia and bipolar disorderaredistinctentities with separate underlying disease processes and treatments. In more recent years there has been increasing evidence for phenomenological, biological and genetic overlap between the two disorders (Potash and Bienvenu 2009). Nowadays, the categorical approach to psychiatric nosography is in contrast with the recent neurobiological, neuropsychological and genetic findings in affective and schizophrenic disorders. Further, symptoms and signs constituting bipolar and schizophrenic disorders are continuously, not dichotomously, distributed; there may be no point of “real cleavage” (Phelps et al. 2008). This recognition has led some clinicians and researchers to call for a diagnostic model that, moving to a “dimensional perspective”, formally recognizes a continuous spectrum from schizophrenic to bipolar (and recurrent depressive) disorders. Kelsoe argued that the existing data coming from various fields of research in bipolar and schizophrenic disorders may best fit a model in which different set of genes predispose to overlapping phenotypes in a continuum. Given the apparent overlap of regions of the genome implicated in bipolar disorder with those for schizophrenia (Kelsoe 1999; Berrettini 2000), the data suggest the possibility that a common polygenic background predisposes to both bipolar disorder and schizophrenia, according to the so-called “multiple threshold model” (Kelsoe 2003). As highlighted by Craddock and Owen, the recent findings are compatible with a model of functional psychosis in which susceptibility to a spectrum of clinical phenotypes is under the influence of overlapping sets of genes, which, together with environmental and epigenetic factors, determine an individual’s expression of illness (Craddock and Owen 2005). A lot of interest is focusing on brain structural abnormalities in patients suffering from schizophrenia and bipolar disorder. A huge amount of neuroimaging studies has been published so far, however the literature is heterogeneous and there is still some degree of uncertainty concerning what key regions are involved in the pathogenesis of such disorders. Schizophrenia and Bipolar Disorder have a number of overlapping symptoms and risk factors, but it is not yet clear if the disorders are characterized by similar deviations in brain morphometry or whether any such deviations reflect the impact of shared susceptibility genes on brain structure. To date there is no consensus about whether, and to what extent, gray matter loss in Schizophrenia is mirrored in Bipolar Disorder and what is the effect of medication or other confounding factors. Studies in family members of patients, who share the risk of the disease but not the confounding factors, may help elucidate whether abnormalities in brain structures are shared by both illnesses. AIM OF THE STUDY: to investigate hippocampal gray matter volume differences in a group of patients with bipolar-schizophrenic spectrum disorders, a group of their unaffected first-degree relatives, and a group of healthy control subjects. METHODS: a total of 104 subjects - 36 schizophrenic or schizoaffective (SZ), 27 bipolar (BP), 2 major depression, 8 unaffected relatives (UR), and 31 healthy controls (HC) - underwent 1,5 T MRI scanning, with volumetric T1 3D acquisition protocol, at the Neuroradiology Unit of Conegliano Hospital. We calculate bilateral hippocampal gray matter volume (HV) and total cerebral volume (TCV) in a sample of 31 SZ, 27 BP, 8 UR and 26 HC, with a stereological method using ANALYZE 10.0 software. RESULTS: we found statistically significant reductions in bilateral HV in the BP-SZ patients compared to HC; the direct comparison between patient groups identified statistically significant reduction in the right HV of SZ, but no significant differences for left HV or TCV (however statistical significance was lost after normalization); statistically significant reduction in the left HV and a trend towards statistical significance for right HV in the UR compared to HC (a trend towards statistically significant reduction in bilateral HV persisted after normalization). CONCLUSION: it might be speculated that the alterations of the gray matter volume in the hippocampus highlighted in our study could be interpreted as a possible structural “biological marker” in the schizophrenic-bipolar spectrum

Correlation between voxel based morphometry and manual volumetry in magnetic resonance images of the human brain

This is a comparative study between manual volumetry (MV) and voxel based morphometry (VBM) as methods of evaluating the volume of brain structures in magnetic resonance images. The volumes of the hippocampus and the amygdala of 16 panic disorder patients and 16 healthy controls measured through MV were correlated with the volumes of gray matter estimated by optimized modulated VBM. The chosen structures are composed almost exclusively of gray matter. Using a 4 mm Gaussian filter, statistically significant clusters were found bilaterally in the hippocampus and in the right amygdala in the statistical parametric map correlating with the respective manual volume. With the conventional 12 mm filter,a significant correlation was found only for the right hippocampus. Therefore,narrowfilters increase the sensitivity of the correlation procedure, especially when small brain structures are analyzed. The two techniques seem to consistently measure structural volume.Trata-se de estudo comparativo entre a volumetria manual(VM) e a morfometria baseada no vóxel (MBV), como métodos de avaliação do volume de estruturas cerebrais. Os volumes do hipocampo e da amídala de 16 pacientes de pânico e 16 controles sadios medidos através da VM foram correlacionados com os volumes de matéria cinzenta estimados pela MBV.As estruturas escolhidas são constituídas quase exclusivamente de matéria cinzenta. Utilizando um filtro Gaussiano de 4 mm, encontram-se, bilateralmente, aglomerados significativos de correlação nas duas estruturas no mapa estatístico paramétrico, correspondendo ao respectivo volume manual. Com o filtro convencional de 12 mm, apenas uma correlação significativa foi encontrada no hipocampo direito. Portanto, filtros estreitos aumentam a sensibilidade do procedimento de correlação,especialmente quando estruturas pequenas são analisadas. Ambas as técnicas parecem medir consistentemente o volume estrutural.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)(FAEPA) Hospital das Clínicas da FMRPUSP - Fundação de Apoio ao Ensino, Pesquisa e Asssistênci

Are Bipolar Disorder and Schizophrenia Neuroanatomically Distinct? An Anatomical Likelihood Meta-analysis

Objective: There is renewed debate on whether modern diagnostic classification should adopt a dichotomous or dimensional approach to schizophrenia and bipolar disorder. This study synthesizes data from voxel-based studies of schizophrenia and bipolar disorder to estimate the extent to which these conditions have a common neuroanatomical phenotype. Methods: A post-hoc meta-analytic estimation of the extent to which bipolar disorder, schizophrenia, or both conditions contribute to brain gray matter differences compared to controls was achieved using a novel application of the conventional anatomical likelihood estimation (ALE) method. 19 schizophrenia studies (651 patients and 693 controls) were matched as closely as possible to 19 bipolar studies (540 patients and 745 controls). Result: Substantial overlaps in the regions affected by schizophrenia and bipolar disorder included regions in prefrontal cortex, thalamus, left caudate, left medial temporal lobe, and right insula. Bipolar disorder and schizophrenia jointly contributed to clusters in the right hemisphere, but schizophrenia was almost exclusively associated with additional gray matter deficits (left insula and amygdala) in the left hemisphere. Limitation: The current meta-analytic method has a number of constraints. Importantly, only studies identifying differences between controls and patient groups could be included in this analysis. Conclusion: Bipolar disorder shares many of the same brain regions as schizophrenia. However, relative to neurotypical controls, lower gray matter volume in schizophrenia is more extensive and includes the amygdala. This fresh application of ALE accommodates multiple studies in a relatively unbiased comparison. Common biological mechanisms may explain the neuroanatomical overlap between these major disorders, but explaining why brain differences are more extensive in schizophrenia remains challenging

Glutamatergic Metabolites and Gray Matter Losses in Schizophrenia: A Longitudinal Study Using In Vivo Proton Magnetic Resonance Spectroscopy

Approximately one in hundred people suffer from schizophrenia. Current medications partially improve the symptoms. There is no cure. Glutamate, an excitatory neurotransmitter, is a possible cause of the schizophrenia symptoms. Excessive glutamate release eventually leads to neurodegeneration. Longitudinal studies are necessary to observe the neurodegenerative process. Seventeen schizophrenia patients and 17 healthy volunteers underwent proton magnetic resonance spectroscopy (MRS) and imaging to measure neurochemical and structural changes in vivo. Metabolite levels were measured from a 1.5cm3 voxel in the anterior cingulate and thalamus using the stimulated echo acquisition mode sequence. Gray matter (GM) was assessed with voxel-based morphometry and ANALYZE. Total glutamatergic metabolite (tGL), N-acetylaspartate (NAA), and GM were significantly decreased in schizophrenia over 80 months. Reduced tGL and NAA levels were significantly correlated with GM changes. tGL loss was negatively correlated with social functioning. Significantly decreased tGL levels were possibly associated with GM loss in the spectroscopy voxel. Metabolite signal-to-noise ratio, but not quantification, was decreased as a function of MR system age. These findings demonstrate the feasibility of long-term MRS studies and implications for the pathophysiology of schizophrenia. tGL and GM losses were consistent with neurodegeneration but the effects of an early neurodevelopmental lesion or the effects of chronic medication cannot be ruled out. Structural and metabolite changes in these patients implicate glutamate as a possible target of medication in this disorder. The association between tGL loss and social functioning suggests it might be possible to arrest deterioration with pharmaceuticals that target glutamate

Neurodegeneration in Schizophrenia: Evidence from In Vivo

Although schizophrenia is primarily considered to be a neurodevelopmental disorder, there is a growing consensus that the disorder may also involve neurodegeneration. Recent research using non-invasive neuroimaging techniques, such as magnetic resonance imaging, suggests that some patients with schizophrenia show progressive losses of gray matter in the frontal and temporal lobes of the brain. The cellular mechanisms responsible for such gray matter losses are unknown, but have been hypothesized to involve abnormal increases in apoptosis

A Review of Structural MRI and Diffusion Tensor Imaging in Schizotypal Personality Disorder

Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity—abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region—abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation—abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia