MRI anatomy of schizophrenia

Article (PDF Available)inBiological Psychiatry 45(9):1099-119 · June 1999with36 Reads
DOI: 10.1016/S0006-3223(99)00018-9 · Source: PubMed
Structural magnetic resonance imaging (MRI) data have provided much evidence in support of our current view that schizophrenia is a brain disorder with altered brain structure, and consequently involving more than a simple disturbance in neurotransmission. This review surveys 118 peer-reviewed studies with control group from 1987 to May 1998. Most studies (81%) do not find abnormalities of whole brain/intracranial contents, while lateral ventricle enlargement is reported in 77%, and third ventricle enlargement in 67%. The temporal lobe was the brain parenchymal region with the most consistently documented abnormalities. Volume decreases were found in 62% of 37 studies of whole temporal lobe, and in 81% of 16 studies of the superior temporal gyrus (and in 100% with gray matter separately evaluated). Fully 77% of the 30 studies of the medial temporal lobe reported volume reduction in one or more of its constituent structures (hippocampus, amygdala, parahippocampal gyrus). Despite evidence for frontal lobe functional abnormalities, structural MRI investigations less consistently found abnormalities, with 55% describing volume reduction. It may be that frontal lobe volume changes are small, and near the threshold for MRI detection. The parietal and occipital lobes were much less studied; about half of the studies showed positive findings. Most studies of cortical gray matter (86%) found volume reductions were not diffuse, but more pronounced in certain areas. About two thirds of the studies of subcortical structures of thalamus, corpus callosum and basal ganglia (which tend to increase volume with typical neuroleptics), show positive findings, as do almost all (91%) studies of cavum septi pellucidi (CSP). Most data were consistent with a developmental model, but growing evidence was compatible also with progressive, neurodegenerative features, suggesting a "two-hit" model of schizophrenia, for which a cellular hypothesis is discussed. The relationship of clinical symptoms to MRI findings is reviewed, as is the growing evidence suggesting structural abnormalities differ in affective (bipolar) psychosis and schizophrenia.

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Available from: Martha E Shenton, Jul 22, 2014
    • "In vivo human neuroimaging investigations have revealed a number of thalamic abnormalities in schizophrenia, including reduced volume (McCarley et al., 1999; Shenton et al., 2001; Glahn et al., 2008), altered activity during cognition (Minzenberg et al., 2009 ), and diminished expression of neurochemical markers of neuronal integrity, such as N-acetyl aspartate (NAA) (Kraguljac et al., 2012) Given the centrality of cognitive impairment, thalamocortical models of schizophrenia emphasize dysfunction of the MD nucleus and, to a lesser extent, the pulvinar (Andreasen et al., 1998; Jones, 1997; Swerdlow, 2010; Cronenwett and Csernansky, 2010). However, evidence for differential involvement of specific nuclei is inconsistent. "
    [Show abstract] [Hide abstract] ABSTRACT: Available online xxxx Brain circuitry underlying cognition, emotion, and perception is abnormal in schizophrenia. There is considerable evidence that the neuropathology of schizophrenia includes the thalamus, a key hub of cortical-subcortical circuitry and an important regulator of cortical activity. However, the thalamus is a heterogeneous structure composed of several nuclei with distinct inputs and cortical connections. Limitations of conventional neuroimaging methods and conflicting findings from post-mortem investigations have made it difficult to determine if thalamic pathology in schizophrenia is widespread or limited to specific thalamocortical circuits. Resting-state fMRI has proven invaluable for understanding the large-scale functional organization of the brain and investigating neural circuitry relevant to psychiatric disorders. This article summarizes resting-state fMRI investigations of thalamocortical functional connectivity in schizophrenia. Particular attention is paid to the course, diagnostic specificity, and clinical correlates of thalamocortical network dysfunction.
    Full-text · Article · Aug 2016
    • "The answer to this question is important in understanding the pathophysiology of schizophrenia and developing therapeutic approaches. P3 may track the course of neurophysiological pathology in schizophrenia because it reflects attentional processes (Polich and Kok, 1995) and cortical gray matter volumes (Ford et al., 1994a), which are both found to be abnormal in schizophrenia (McCarley et al., 1999; Mesholam-Gately et al., 2009). Indeed, P3 amplitude reduction in schizophrenia has been related to attentional and gray matter deficits (Grillon et al., 1990; McCarley et al., 1993 McCarley et al., , 2002). "
    [Show abstract] [Hide abstract] ABSTRACT: P3 event-related potential may track the course of neurophysiological pathology in schizophrenia. Reduction in the amplitude of the auditory P3 is a widely replicated finding, already present at the first psychotic episode, in schizophrenia. Whether a progressive deficit is present in auditory P3 in schizophrenia over the course of illness is yet to be clarified. Previous longitudinal studies did not report any change in P3 over time in schizophrenia. However, these studies have been inconclusive, because of their relatively short follow-up periods, lack of follow-up data on controls, and assessment of patients already at the chronic stages of schizophrenia. Auditory P3 potentials, elicited by an oddball paradigm, were assessed in 14 patients with first-episode schizophrenia and 22 healthy controls at baseline and at the 6-year follow-up. P3 amplitudes were smaller in patients with first-episode schizophrenia than in controls. Importantly, over the 6-year interval, the P3 amplitudes were reduced in controls, but they did not change in patients. The lack of P3 reduction over time in patients with schizophrenia might be explained by the maximal reduction in P3 already at baseline or by the alleviation of P3 reduction over time.
    Full-text · Article · Jun 2016
    • "This phenomenon of stress exacerbation is known as the dual hit or two hit hypothesis of neurodegeneration (Carvey et al., 2006; Leak, 2014). Many authors have applied the dual hit hypothesis to the hippocampus, in terms of epilectic seizure activity, schizophrenia, temporal sclerosis, memory loss, and Alzheimer's disease (Dalton et al., 2012; Hamelin and Depaulis, 2015; Hill et al., 2014; Hoffmann et al., 2004; Lewis, 2005; Llorente et al., 2011; McCarley et al., 1999; Ouardouz et al., 2010; Somera-Molina et al., 2007; Zhu et al., 2007). However, there is no model of synergistic cell death in hippocampal neurons in response to sequential hits of proteotoxic and oxidative stressors, the two major features of neurodegenerative disorders. "
    [Show abstract] [Hide abstract] ABSTRACT: The dual hit hypothesis of neurodegeneration states that severe stress sensitizes vulnerable cells to subsequent challenges so that the two hits are synergistic in their toxic effects. Although the hippocampus is vulnerable to a number of neurodegenerative disorders, there are no models of synergistic cell death in hippocampal neurons in response to combined proteotoxic and oxidative stressors, the two major characteristics of these diseases. Therefore, we developed a relatively high-throughput dual hit model of stress synergy in primary hippocampal neurons. In order to increase the rigor of our study and strengthen our interpretations, we employed three independent, unbiased viability assays at multiple timepoints. Stress synergy was elicited when hippocampal neurons were treated with the proteasome inhibitor MG132 followed by exposure to the oxidative toxicant paraquat, but only after 48h. MG132 and paraquat only elicited additive effects 24h after the final hit and even loss of heat shock protein 70 activity and glutathione did not promote stress synergy at this early timepoint. Dual hits of MG132 elicited modest glutathione loss and slightly synergistic toxic effects 48h after the second hit, but only at some concentrations and only according to two viability assays (metabolic fitness and cytoskeletal integrity). The thiol N-acetyl cysteine protected hippocampal neurons against dual MG132/MG132 hits but not dual MG132/paraquat hits. Our findings support the view that proteotoxic and oxidative stress propel and propagate each other in hippocampal neurons, leading to synergistically toxic effects, but not as the default response and only after a delay. The neuronal stress synergy observed here lies in contrast to astrocytic responses to dual hits, because astrocytes that survive severe proteotoxic stress resist additional cell loss following second hits. In conclusion, we present a new model of hippocampal vulnerability in which to test therapies, because neuroprotective treatments that are effective against severe, synergistic stress are more likely to succeed in the clinic. This article is protected by copyright. All rights reserved.
    Full-text · Article · Mar 2016
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