A review of MRI findings in schizophrenia.Schizophr. Res. 49(1-2), 1-52

Clinical Neuroscience Division, Laboratory of Neuroscience, Department of Psychiatry, Harvard Medical School, Brockton, MA 02301, USA.
Schizophrenia Research (Impact Factor: 3.92). 05/2001; 49(1-2):1-52. DOI: 10.1016/S0920-9964(01)00163-3
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ABSTRACT After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin, E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described 'dementia praecox' and the 'schizophrenias', were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82-120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137-147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi-92% of studies reviewed, basal ganglia-68% of studies reviewed, corpus callosum-63% of studies reviewed, and thalamus-42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. (ABSTRACT TRUNCATED)

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Available from: Martha E Shenton, Sep 28, 2015
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    • "Onset is during adolescence or young adulthood, and it is often lifelong and chronic. Although progress has been made in delineating brain abnormalities in schizophrenia (Fitzsimmons et al., 2013), the etiology, pathogenesis, and biological course still remain elusive, with evidence suggesting a variety of deficiencies and abnormalities, including neurodevelopmental and neurodegenerative abnormalities, as well as a number of dopaminergic, myelin, oligodendrocyte , and volumetric alterations in a number of brain regions that are not proximal but may reflect an underlying anatomical and or functional connection (e.g., see reviews in Harrison, 1999; Jaaro-Peled et al., 2010; Kubicki et al., 2005; Shenton et al., 2001). "
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    ABSTRACT: In recent years evidence has accumulated to suggest that neuroinflammation might be an early pathology of schizophrenia that later leads to neurodegeneration, yet the exact role in the etiology, as well as the source of neuroinflammation, are still not known. The hypothesis of neuroinflammation involvement in schizophrenia is quickly gaining popularity, and thus it is imperative that we have reliable and reproducible tools and measures that are both sensitive, and, most importantly, specific to neuroinflammation. The development and use of appropriate human in vivo imaging methods can help in our understanding of the location and extent of neuroinflammation in different stages of the disorder, its natural time-course, and its relation to neurodegeneration. Thus far, there is little in vivo evidence derived from neuroimaging methods. This is likely the case because the methods that are specific and sensitive to neuroinflammation are relatively new or only just being developed. This paper provides a methodological review of both existing and emerging positron emission tomography and magnetic resonance imaging techniques that identify and characterize neuroinflammation. We describe \how these methods have been used in schizophrenia research. We also outline the shortcomings of existing methods, and we highlight promising future techniques that will likely improve state-of-the-art neuroimaging as a more refined approach for investigating neuroinflammation in schizophrenia. Copyright © 2015 Elsevier B.V. All rights reserved.
    Schizophrenia Research 06/2015; DOI:10.1016/j.schres.2015.05.034 · 3.92 Impact Factor
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    • "Schizophrenia has long been conceptualized as a " dysconnectivity syndrome " [Friston, 1998] in that the interconnections between modular systems in the brain are awry [David, 1994]. Several neuroimaging studies using magnetic resonance imaging (MRI) have uncovered dysconnectivity in several neural pathways using both structural and functional neuroimaging [Pettersson-Yeo et al., 2011; Shenton et al., 2001; Wheeler and Voineskos, 2014] and have suggested that they may arise early in the course of, or even predate the disorder [Carletti et al., 2012]. The heterogeneity of structures that are implicated in schizophrenia suggests that the associated abnormalities manifest globally, rather than being focal to one particular region or pathway. "
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    ABSTRACT: Schizophrenia is often regarded as a "dysconnectivity" disorder and recent work using graph theory has been used to better characterize dysconnectivity of the structural connectome in schizophrenia. However, there are still little data on the topology of connectomes in less severe forms of the condition. Such analysis will identify topological markers of less severe disease states and provide potential predictors of further disease development. Individuals with psychotic experiences (PEs) were identified from a population-based cohort without relying on participants presenting to clinical services. Such individuals have an increased risk of developing clinically significant psychosis. 123 individuals with PEs and 125 controls were scanned with diffusion-weighted MRI. Whole-brain structural connectomes were derived and a range of global and local GT-metrics were computed. Global efficiency and density were significantly reduced in individuals with PEs. Local efficiency was reduced in a number of regions, including critical network hubs. Further analysis of functional subnetworks showed differential impairment of the default mode network. An additional analysis of pair-wise connections showed no evidence of differences in individuals with PEs. These results are consistent with previous findings in schizophrenia. Reduced efficiency in critical core hubs suggests the brains of individuals with PEs may be particularly predisposed to dysfunction. The absence of any detectable effects in pair-wise connections illustrates that, at less severe stages of psychosis, white-matter alterations are subtle and only manifest when examining network topology. This study indicates that topology could be a sensitive biomarker for early stages of psychotic illness. Hum Brain Mapp, 2015.© 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 04/2015; 36:2629–2643. DOI:10.1002/hbm.22796 · 5.97 Impact Factor
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    • "Reduced hippocampal volume has been consistently reported in this population (Eliez et al., 2000; Kates et al., 2001, 2004, 2006; Simon et al., 2005c; Campbell et al., 2006; Debbané et al., 2006; Deboer et al., 2007) and was significantly correlated with lower verbal IQ (Deboer et al., 2007). Alterations of the hippocampal formation are considered to be a biomarker for schizophrenia and tend to show a similar pattern of functional relationships to that described above (for review, see Shenton et al., 2001). Despite the important role that the hippocampus plays in core cognitive, affective and behavioral aspects of the 22q11.2DS "
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    ABSTRACT: The fornix is the primary subcortical output fiber system of the hippocampal formation. In children with 22q11.2 deletion syndrome (22q11.2DS), hippocampal volume reduction has been commonly reported, but few studies as yet have evaluated the integrity of the fornix. Therefore, we investigated the fornix of 45 school-aged children with 22q11.2DS and 38 matched typically developing (TD) children. Probabilistic diffusion tensor imaging (DTI) tractography was used to reconstruct the body of the fornix in each child׳s brain native space. Compared with children, significantly lower fractional anisotropy (FA) and higher radial diffusivity (RD) was observed bilaterally in the body of the fornix in children with 22q11.2DS. Irregularities were especially prominent in the posterior aspect of the fornix where it emerges from the hippocampus. Smaller volumes of the hippocampal formations were also found in the 22q11.2DS group. The reduced hippocampal volumes were correlated with lower fornix FA and higher fornix RD in the right hemisphere. Our findings provide neuroanatomical evidence of disrupted hippocampal connectivity in children with 22q11.2DS, which may help to further understand the biological basis of spatial impairments, affective regulation, and other factors related to the ultra-high risk for schizophrenia in this population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Psychiatry Research: Neuroimaging 02/2015; 232(1). DOI:10.1016/j.pscychresns.2015.02.002 · 2.42 Impact Factor
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