It is important to elaborate what we know about the symptomatic, syndromal, and functional course of schizophrenia in order to test models for this illness. The sample of schizophrenic patients from the Chestnut Lodge followup study was subtyped using classical (modified DSMHI-R) criteria and deficit/ nondeficit (Schedule for the Deficit Syndrome) criteria. During the first 5 years of manifest illness, the subtype phenomenologies were moderately stable. Instability consisted of a drift toward disorganization (hebephrenia) and nonspecificity (undifferentiated) among the classical subtypes, and toward the deficit subtype within that categorization. Over the same time, positive symptoms were relatively stable, but negative symptoms became significantly worse. Such changes probably reflect "deterioration" because they were associated with poorer functional outcome an average of 15 years later. These data dovetail with other reports in the literature and suggest a hierarchy of symptomatic/s yndromal progression in early manifest schizophrenia that may reflect active deterioration processes at work. We suggest that any theory of schizophrenic pathophysiology must account for these patterns of symptom course.

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Polydipsia-hyponatremia: Evidence for specific cerebral structural pathology and implications for the pathophysiology of schizophrenia

Subtype Progression and Pathophysiologic Deterioration in Early Schizophrenia

Cuprizone-induced demyelination in mice is a frequently used model in preclinical multiple sclerosis research. A recent quantitative clinically-targeted MRI method, fast macromolecular proton fraction (MPF) mapping demonstrated a promise as a myelin biomarker in human and animal studies with a particular advantage of sensitivity to both white matter (WM) and gray matter (GM) demyelination. This study aimed to histologically validate the capability of MPF mapping to quantify myelin loss in brain tissues using the cuprizone demyelination model. Whole-brain MPF maps were obtained in vivo on an 11.7T animal MRI scanner from 7 cuprizone-treated and 7 control С57BL/6 mice using the fast single-point synthetic-reference method. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. Significant (p < 0.05) demyelination in cuprizone-treated animals was found according to both LFB staining and MPF in all anatomical structures (corpus callosum, anterior commissure, internal capsule, thalamus, caudoputamen, and cortex). MPF strongly correlated with quantitative histology in all animals (r = 0.95, p < 0.001) as well as in treatment and control groups taken separately (r = 0.96, p = 0.002 and r = 0.93, p = 0.007, respectively). Close agreement between histological myelin staining and MPF suggests that fast MPF mapping enables robust and accurate quantitative assessment of demyelination in both WM and GM.

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Polydipsia-hyponatremia: Evidence for specific cerebral structural pathology and implications for the pathophysiology of schizophrenia

Citations

Subtype Progression and Pathophysiologic Deterioration in Early Schizophrenia

Histological validation of fast macromolecular proton fraction mapping as a quantitative myelin imaging method in the cuprizone demyelination model

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