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Annotation

Salisbury DF, Kuroki N, Kasai K, Shenton ME, McCarley RW. Progressive and interrelated functional and structural evidence of post-onset brain reduction in schizophrenia. Arch Gen Psychiatry . 2007 May 1 ; 64(5):521-9. PubMed Abstract

Comments on Paper and Primary News
Primary News: Schizophrenia and Neurodegeneration—Case Bolstered by MRI, Electrophysiology

Comment by:  Dan Javitt, SRF Advisor
Submitted 29 May 2007 Posted 29 May 2007

Salisbury et al., in the May 2007 issue of Archives of General Psychiatry, demonstrate associated progressive reductions in mismatch negativity (MMN) amplitude and Heschl’s gyrus reduction in schizophrenia. These findings provide strong support for involvement of auditory cortex in the pathogenesis of schizophrenia, and demonstrate that pathological changes in the illness are not confined to specific brain regions, such as prefrontal cortex, that receive the preponderance of attention.

Further, the manuscript helps resolve an important current controversy in the MMN literature. Deficits in MMN generation have been among the most consistent findings in chronic schizophrenia, with a recent meta-analysis showing large (~1 sd unit) effect size MMN reductions across studies (Umbricht et al., 2005). As noted by Salisbury et al., however, deficits have not been observed in first-episode patients (Salisbury et al., 2002; Umbricht et al., 2006)....  Read more


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Primary News: Schizophrenia and Neurodegeneration—Case Bolstered by MRI, Electrophysiology

Comment by:  Lei Wang
Submitted 5 June 2007 Posted 5 June 2007

The authors reported a cross-sectional (first hospitalization or within 1 year of first hospitalization) and longitudinal (1.5-year follow-up) study of electrophysiologic testing (mismatch negativity, or MMN, amplitude) and high-resolution structural magnetic resonance imaging of Heschl gyrus and planum temporale gray matter volumes. Schizophrenia subjects showed longitudinal volume reduction of left hemisphere Heschl gyrus (P = .003), which was highly correlated with MMN reduction (r = 0.6; P = .04). The interrelated progressive reduction of functional and structural measures suggests progressive pathologic processes early in schizophrenia. The design of the study helped minimize the effect of medication, the authors commented, therefore allowing the interpretation that brain change is due to disease progression.

From an imaging perspective, this is a straightforward longitudinal study of brain structure following previously published image processing and measuring protocols (Kasai et al., 2003). T1- and T2-weighted MR scans...  Read more


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Primary News: Schizophrenia and Neurodegeneration—Case Bolstered by MRI, Electrophysiology

Comment by:  Robert McClure (Disclosure)
Submitted 10 June 2007 Posted 10 June 2007

Longitudinal increases in volume of the lateral ventricles and decreases in brain volume—progressive changes—are often observed over time early in the course of schizophrenia. There is not uniform agreement over the proper interpretation of these changes, prompting vigorous, healthy debate among investigators. A major point of contention appears to be whether these volume changes actually constitute evidence of active disease progression.

In the current study, the authors seek to bolster the case for structural progression by demonstrating evidence of interrelated progressive functional impairment. They buttress the case for structural progression by demonstrating a relationship between worsening deficit in mismatch negativity and auditory cortex volume decreases.

Identification of a direct causal relationship between the underlying pathophysiology of schizophrenia and volume losses observed early in the illness would conclusively demonstrate structural progression. Such a direct link has not yet been established, so the results of this study constitute...  Read more


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