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

Harvard University, Cambridge, Massachusetts, United States
Schizophrenia Research (Impact Factor: 3.92). 05/2001; 49(1-2):1-52. DOI: 10.1016/S0920-9964(01)00163-3
Source: PubMed


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
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    • "Schizophrenia patients consistently display lower brain volumes and reduced cortical thickness when compared to healthy controls (Edgar et al., 2012;Kuperberg et al., 2003;Olabi et al., 2011;Shenton et al., 2001;van Haren et al., 2011;Venkatasubramanian et al., 2008). However, there is growing evidence of heterogeneity of brain structural patterns in schizophrenia patients. "
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    ABSTRACT: Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. Patient subgroups were based on an established clinical threshold of − 1.4 z-score on the International Shopping List Task of the CogState battery. A series of between-group vertex-wise general linear models on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe (predominantly in the left middle frontal gyrus, the inferior frontal gyrus, the orbitofrontal gyrus and precentral gyrus), and the bilateral parahippocampal gyri (p < .05 FDR corrected). When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex (p < .05 uncorrected) in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls, even with a liberal threshold (p < .05 uncorrected). No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments also demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM impairments in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments.
    Full-text · Article · Dec 2015 · Clinical neuroimaging
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    • "Increases in the volume of lateral ventricles (LVs) were among the first identified abnormalities in schizophrenia (Johnstone et al., 1976) and since that time increases in LVs volume remain among the most reliable volumetric abnormalities reported in schizophrenia (Kempton et al., 2010; Nakamura et al., 2007; Shenton et al., 2001). Such increases are present not only in chronic schizophrenia patients but also in the early stages of disease (Nakamura et al., 2007; Shenton et al., 2001). Changes in the corpus callosum (CC) are also described in schizophrenia, where the midsagittal area of the CC has been reported to be decreased in schizophrenia patients (Woodruff et al., 1995), with effects more detectable in first episode than chronic schizophrenia (Arnone et al., 2008). "
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    ABSTRACT: The lateral and third ventricles, as well as the corpus callosum (CC), are known to be affected in schizophrenia. Here we investigate whether abnormalities in the lateral ventricles (LVs), third ventricle, and corpus callosum are related to one another in first episode schizophrenia (FESZ), and whether such abnormalities show progression over time. Nineteen FESZ and 19 age- and handedness-matched controls were included in the study. MR images were acquired on a 3-Tesla MRI at baseline and ~1.2 years later. FreeSurfer v.5.3 was employed for segmentation. Two-way or univariate ANCOVAs were used for statistical analysis, where the covariate was intracranial volume. Group and gender were included as between-subjects factors. Percent volume changes between baseline and follow-up were used to determine volume changes at follow-up. Bilateral LV and third ventricle volumes were significantly increased, while central CC volume was significantly decreased in patients compared to controls at baseline and at follow-up. In FESZ, the bilateral LV volume was also inversely correlated with volume of the central CC. This inverse correlation was not present in controls. In FESZ, an inverse correlation was found between percent volume increase from baseline to follow-up for bilateral LVs and lesser improvement in the Global Assessment of Functioning score. Significant correlations were observed for abnormalities of central CC, LVs and third ventricle volumes in FESZ, suggesting a common neurodevelopmental origin in schizophrenia. Enlargement of ventricles was associated with less improvement in global functioning over time.
    Full-text · Article · Dec 2015 · Brain Imaging and Behavior
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    • "Here, we extend these findings to an examination of LTC structure. Research on altered LTC structure in schizophrenia has focused most often on the STG (Shenton et al., 2001). Given its well-established role in language perception and production (Price, 2010), it is thought that STG structural abnormalities may contribute to impaired integration of language and memory processes (Stephan et al., 2009) that could underlie positive symptoms in schizophrenia (e.g., auditory hallucinations and thought disorder) — a hypothesis supported by recent meta-analyses (Palaniyappan et al., 2012a; Palaniyappan et al., 2012b). "
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    ABSTRACT: Background: Structural alterations of the lateral temporal cortex (LTC) in association with memory impairments have been reported in schizophrenia. This study investigated whether alterations of LTC structure were linked with impaired facial and/or verbal memory in young first-degree relatives of people with schizophrenia and, thus, may be indicators of vulnerability to the illness. Methods: Subjects included 27 non-psychotic, first-degree relatives of schizophrenia patients, and 48 healthy controls, between the ages of 13 and 28. Participants underwent high-resolution magnetic resonance imaging (MRI) at 1.5Tesla. The LTC was parcellated into superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, and temporal pole. Total cerebral and LTC volumes were measured using semi-automated morphometry. The Wechsler Memory Scale - Third Edition and the Children's Memory Scale - Third Edition assessed facial and verbal memory. General linear models tested for associations among LTC subregion volumes, familial risk and memory. Results: Compared with controls, relatives had significantly smaller bilateral middle temporal gyri. Moreover, right middle temporal gyral volume showed a significant positive association with delayed facial memory in relatives. Conclusion: These results support the hypothesis that smaller middle temporal gyri are related to the genetic liability to schizophrenia and may be linked with reduced facial memory in persons at genetic risk for the illness. The findings add to the growing evidence that children at risk for schizophrenia on the basis of positive family history have cortical and subcortical structural brain abnormalities well before psychotic illness occurs.
    Full-text · Article · Nov 2015 · Schizophrenia Research
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