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
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)


Available from: Martha E Shenton
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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). "

    Schizophrenia Research 11/2015; DOI:10.1016/j.schres.2015.11.013 · 3.92 Impact Factor
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    • "ACE also influence brain activity in response to emotional stimuli in amygdala, hippocampus, prefrontal, and cingulate cortex, affecting GM structure and function in healthy controls (HC) and in patients with SCZ (Benedetti et al., 2011a; Dannlowski et al., 2012b; Dannlowski et al., 2012a; Taylor et al., 2006). Compared with HC, reduced volumes of GM have been consistently described in patients with SCZ (Kawasaki et al., 2004; Shenton et al., 2001; Wright et al., 2000) and BD (Arnone et al., 2009; Baumann and Bogerts, 1999; Kempton et al., 2008). However, only few studies have addressed the issue of volumetric differences between patients with BD and SCZ revealing considerable heterogeneity. "
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    ABSTRACT: Background: Adverse childhood experiences (ACE) can lead to several negative consequences in adult life, are highly prevalent in psychiatric disorders where they associate with clinical and brain morphological features. Grey matter volume loss is a central characteristic of bipolar disorder (BD) and schizophrenia (SCZ). The aim of this study is to measure the effect of diagnosis and ACE on GM volume in a sample of patients with BD or SCZ compared with healthy controls (HC). Methods: We studied 206 depressed BD patients, 96 SCZ patients and 136 healthy subjects. GM volumes were estimated with 3.0 Tesla MRI and analyzed with VBM technique. The effect of diagnosis was investigated in the whole sample and separately exposed to high and low ACE subjects. Results: An effect of diagnosis was observed in orbitofrontal cortex encompassing BA 47 and insula, and in the thalamus. HC had the highest volume and SCZ patients the lowest with BD patients showing an intermediate volume. This pattern persisted only in subjects with high ACE. No differences were observed for low ACE subjects. Limitations: The three diagnostic groups differ for age and education, previous and current medications, and treatment periods. Conclusions: Our results underline the importance of ACE on the neural underpinnings of psychiatric psychopathology and suggest a major role of exposure to ACE for the GM deficits to reveal in clinical populations. Exposure to early stress is a crucial factor that must be taken in to account when searching for biomarkers of BD and SCZ.
    Journal of Affective Disorders 10/2015; 189:290-297. DOI:10.1016/j.jad.2015.09.049 · 3.38 Impact Factor
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    • "There is a significant overlap in the neural circuitry that subserves olfactory and emotional processing as well as the pathophysiology of schizophrenia, including the orbitofrontal cortex (OFC), the amygdala, the hippocampus and the parahippocampal gyrus (the entorhinal and perirhinal cortices) (Harrison, 1999; Shenton et al., 2001; Esiri and Crow, 2002; Gottfried and Zald, 2005; Schneider et al., 2007; Kamath et al., 2013). Therefore, it is interesting to investigate the role of the above-mentioned brain regions in the association between olfactory function and hedonic traits. "
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    ABSTRACT: Previous studies have established a linkage between olfactory deficits and negative symptoms in schizophrenia. However, it is not known whether olfactory function is associated with hedonic traits in individuals with schizotypy. Seventeen individuals with schizotypy and 18 age- and sex-matched controls participated in this study. Hedonic traits were assessed with the Chapman Scales for Physical and Social Anhedonia (CSAS and CPAS). Olfactory function was assessed with the Sniffin' Stick Test (olfactory threshold, odour discrimination and odour identification). All participants undertook a structural imaging scan for grey matter volume measurements. Individuals with schizotypy had significantly higher CSAS and CPAS scores than healthy controls. They had normal olfactory function. Their odour identification ability was inversely correlated with physical and social anhedonia. The volume of the right parahippocampal gyrus was positively associated with odour identification ability, and negatively associated with physical and social anhedonia. Furthermore, mediation analysis suggested that odour identification ability influences anhedonia through its effect on the right parahippocampal gyrus. No such relationship was found in controls. These findings suggest that there is a relationship between odour identification and anhedonia in individuals with schizotypy, and the association may be mediated by parahippocampal gyrus volume.
    09/2015; 234(2). DOI:10.1016/j.pscychresns.2015.09.011
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