Reduction in cortical thickness in treatment-resistant schizophrenia

Reduced grey-matter volume and cortical thickness are well documented in people with schizophrenia, but few studies have examined structural changes in treatment-resistant schizophrenia (TRS). In this study from Brazil, the researchers examined cortical thickness by means of MRI volumetrics in three groups: 61 patients with TRS, 67 patients with non-TRS, and 80 unaffected controls (1). The mean age of all subjects was about 34 years and two-thirds were men. The mean PANSS score of the TRS group was 63.4, significantly greater than the mean score of the non-TRS group which was 54.6. Of the TRS patients, 72% were receiving clozapine whereas the majority of non-TRS patients were receiving either olanzapine, quetiapine, or risperidone.

In comparison with the control group, the TRS group had significant reduction in cortical thickness in four regions of the right hemisphere, including the precentral, middle temporal, and lateral occipital gyri; and six regions of the left hemisphere, including the middle temporal, middle frontal, lateral orbitofrontal, and superior temporal gyri. In comparing the TRS and non-TRS groups, the investigators found a significant reduction in thickness of the left dorsolateral prefrontal cortex in the TRS patients, even when controlling for duration of illness and dose of medication.

The investigators cite existing research suggesting that dysfunction of the dorsolateral prefrontal cortex, which is associated with working memory in healthy subjects, may correlate with poor treatment response. For instance, a 2003 study found that greater cortical volume in this region predicts good response to clozapine (2). Studies that examine the dynamics of volume loss prospectively might help determine the correlates of regional cortical thinning in TRS.

1. Zugman A, Gadelha A, Assuncao I, et al. Reduced dorso-lateral prefrontal cortex in treatment resistant schizophrenia. Schizophr Res. 30 May 2013. doi: 10.1016/j.schres.2013.05.002. [Epub ahead of print] Abstract

2. Molina V, Reig S, Sarramea F, et al. Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia. Psychiatry Res. 2003;124(3):153-161. Abstract

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