Neuroimaging biomarkers to predict treatment response in schizophrenia: the end of 30 years of solitude?

Abstract

Studies that have used structural magnetic resonance imaging (MRI) suggest that individuals with psychoses have brain alterations, particularly in frontal and temporal cortices, and in the white matter tracts that connect them. Furthermore, these studies suggest that brain alterations may be particularly prominent, already at illness onset, in those individuals more likely to have poorer outcomes (eg, higher number of hospital admissions, and poorer symptom remission, level of functioning, and response to the first treatment with antipsychotic drugs). The fact that, even when present, these brain alterations are subtle and distributed in nature, has limited, until now, the utility of MRI in the clinical management of these disorders. More recently, MRI approaches, such as machine learning, have suggested that these neuroanatomical biomarkers can be used for direct clinical benefits. For example, using support vector machine, MRI data obtained at illness onset have been used to predict, with significant accuracy, whether a specific individual is likely to experience a remission of symptoms later on in the course of the illness. Taken together, this evidence suggests that validated, strong neuroanatomical markers could be used not only to inform tailored intervention strategies in a single individual, but also to allow patient stratification in clinical trials for new treatments.

Keywords: first-episode schizophrenia; magnetic resonance imaging; psychosis.

Figure 1.. White matter maps of differences between nonresponders and responders. The figure shows areas of significantly decreased fractional anisotropy in nonresponders when compared with responders, at baseline (A) (P<0.05; Family-Wise Error [FEW]-corrected) and at 1 2-week follow-up (B) (P<0.05; FWE-corrected). Fractional anisotropy white matter skeleton is represented by green voxels displayed on a background image that corresponds to the mean fractional anisotropy image in standard Montreal Neurological Institute (MNI) MNI152 brain space (radiological view), with the coordinate number on top. Red-yellow voxels represent regions in which the fractional anisotropy was significantly lower in the nonresponder group relative to the responder group. From reference 33: Reis Marques TR, Taylor H, Chaddock CA, et al White matter integrity as predictor of response to treatment in first episode psychosis. Brain. 2014;137:172-182. © 2013, Oxford University Press.

Figure 2.. Voxel clusters showing differences in gyrification among responders, nonresponders, and healthy controls. Clusters of spatially contiguous suprathreshold voxels indicating higher gyrification for each between-group comparison are displayed in red, yellow, and purple. There were no clusters of reduced gyrification in these between-group comparisons. All clusters are displayed on a reconstructed average white matter surface (fsaverage in the FreeSurfer software) and sun/ived multiple testing using Monte Carlo simulation with a cluster inclusion criterion of P=0.05. The left hemisphere is on the left side of the image, and the right hemisphere is on the right side. The exact values of dusterwise probability for the clusters are presented in Table III. From reference 32: Paianiyappan L, Marques TR, Taylor H, et al Cortical folding defects as markers of poor treatment response in first-episode psychosis. JAMA Psychiatry. 2013;70:1031-1040. Copyright © 2013, American Medical Association.