Longitudinal study of brain morphology in first episode schizophrenia.
ABSTRACT Beginning with Kraepelin, schizophrenia has been viewed as a progressive disorder. Although numerous studies of the longitudinal course of schizophrenia have demonstrated the clinical deterioration that occurs predominantly in the early stages of the illness, the pathophysiology of this clinical phenomenon has not been established. This aspect of the illness may be of critical importance to understanding the pathogenesis of schizophrenia and determining preventive therapeutic strategies. Abnormalities in brain morphology have been consistently described in schizophrenia, but it is not known when in the natural history of the illness they arise and whether they are progressive. Previous studies of brain morphology have been inconclusive, in part because of the variability of methods for image acquisition and analysis, assessment of patients already at chronic stages of their illness with extensive prior treatment exposure, and inadequate periods of follow-up.
To address these questions we examined 107 patients in their first episode of schizophrenia or schizoaffective disorder and 20 healthy volunteers using high resolution magnetic resonance imaging (MRI) and clinical assessments of psychopathology and treatment outcome for periods of up to 6 years. Fifty-one patients and 13 control subjects had MRIs after at least 12 months of follow-up.
Results confirm the findings of ventricular enlargement and anterior hippocampal volume reductions in first episode schizophrenia patients that have been previously reported. In addition, we found changes in selected structures over time in relation to treatment outcome, including increases in ventricular volume that were associated with poor outcome patients. Contrary to our hypothesis, there were no significant reductions in cortical and hippocampal volumes over time.
The finding of progressive ventricular enlargement in patients with poor outcome schizophrenia is consistent with the hypothesis that persistent positive and negative symptoms result in progressive brain changes in the form of ventricular enlargement, possibly due to neurodegeneration rather than the confounding effects of treatment. Future studies of first episodes of schizophrenia should utilize higher resolution imaging techniques that compare clinically well characterized patients with and without poor outcome and recurrent symptoms to control subjects who are well matched to patients for age and gender. There is also a need to control for treatment effects of typical antipsychotic medication on brain structure.
- SourceAvailable from: Martha E Shenton[Show abstract] [Hide abstract]
ABSTRACT: INTRODUCTION: There is converging evidence supporting hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in schizophrenia spectrum disorders (SSD), such as schizotypal personality disorder (SPD), first-episode schizophrenia (FESZ) and chronic schizophrenia (CHSZ). Such an aberrant HPA activity might have volumetric consequences on the pituitary gland. However, previous magnetic resonance imaging (MRI) studies assessing pituitary volume (PV) in SSD are conflicting. The main objective of this study was to examine further PV in SSD. METHODS: PV were manually traced on structural MRIs in 137 subjects, including subjects with SPD (n=40), FESZ (n=15), CHSZ (n=15), and HC (n=67). We used an ANCOVA to test PV between groups and gender while controlling for inter-subject variability in age, years of education, socioeconomic status, and whole brain volume. RESULTS: Overall, women had larger PV than men, and within the male sample all SSD subjects had smaller PV than HC, statistically significant only for the SPD group. In addition, dose of medication, illness duration and age of onset were not associated with PV. CONCLUSION: Chronic untreated HPA hyperactivity might account for smaller PV in SPD subjects, whereas the absence of PV changes in FESZ and CHSZ patients might be related to the normalizing effects of antipsychotics on PV. SPD studies offer a way to examine HPA related alterations in SSD without the potential confounds of medication effects.Schizophrenia Research 03/2013; 146(1-3). DOI:10.1016/j.schres.2013.02.024 · 4.43 Impact Factor
Dataset: PsychMed broome 2010