Differential effects of typical and atypical antipsychotics on brain myelination in schizophrenia

Abstract

Context-Imaging and post-mortem studies provide converging evidence that patients with schizophrenia have a dysregulated developmental trajectory of frontal lobe myelination even in adulthood. Atypical antipsychotics have been shown to have a wide spectrum of efficacy across multiple psychiatric diseases and to be particularly efficacious in treatment resistant cases of disorders such as schizophrenia.Objective-To test the a priori hypothesis that antipsychotic medications may differentially impact frontal lobe myelination in patients with schizophrenia.Design, setting, and participants-Participants ranged in age from 18-35 years, were all male, and were recruited by a single group of investigators using the same criteria. Two cohorts of subjects with schizophrenia early in their disease who were treated either with oral risperidone (Ris) or fluphenazine decanoate (Fd) were imaged in conjunction with cohorts of healthy controls. Each cohort was imaged using a different MRI instrument using identical imaging sequences. Main outcome measure-MRI measures of frontal lobe white matter volume.Results-We estimated differences due to differences in the MRI instruments used in the two studies in the two healthy control groups matched to the patient samples, adjusting for age and other covariates. We then statistically removed those differences (which we assumed were instrument artifacts) from the data in the schizophrenia samples by subtraction. Relative to the differences seen in controls, the two groups of schizophrenic patients differed in their pattern of frontal lobe structure with the Ris-treated group having significantly larger white matter volume than the Fd group.

Brain Diffusion Changes in Emerging Psychosis and the Impact of State-Dependent Psychopathology

“…A recent DTI study showed that FA findings in FEP depended on the size of the studied sample [34]. More longitudinal study designs with large sample and uniform medication strategies, given that atypical and typical antipsychotics may differentially affect myelination in patients [50], are needed to draw robust conclusions on treatment responses. Future studies should also address comorbidities as they could be major sources of hetereogeneity in the biology of high-risk samples [51].…”

Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

“…9,55 In addition, other reports have shown increased levels of serum lipids in patients treated with…”

White Matter Changes Associated with Antipsychotic Treatment in First-Episode Psychosis

“…There are, however, limited longitudinal in-vivo data regarding the potential impact of antipsychotics on the brain, and, in particular, the white matter. Some studies suggest that antipsychotics may have an important therapeutic role in promoting myelination through their effects on oligodendrocytes (Walterfang et al, 2011;Bartzokis et al, 2011), with some empirical work suggesting a protective or myelin-inducing effect of risperidone on the brain white matter (Bartzokis et al, 2007(Bartzokis et al, , 2011Bartzokis et al, 2009). Similarly, animal studies noted that antipsychotic treatment following administration of the copper chelator, cuprizone, promoted oligodendrocyte development and remyelination (Xiao et al, 2008;Zhang et al, 2012), which was evident from magnetic resonance (MR) imaging and confirmed by histological measures (Chandran et al, 2012).…”