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. 2015 May;164(1-3):164-75.
doi: 10.1016/j.schres.2015.01.043. Epub 2015 Feb 13.

Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia

Shinichiro Nakajima  1 , Hiroyoshi Takeuchi  2 , Eric Plitman  3 , Gagan Fervaha  4 , Philip Gerretsen  5 , Fernando Caravaggio  6 , Jun Ku Chung  7 , Yusuke Iwata  8 , Gary Remington  9 , Ariel Graff-Guerrero  10
Affiliations

Neuroimaging findings in treatment-resistant schizophrenia: A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia

Shinichiro Nakajima et al. Schizophr Res. 2015 May.

Abstract

Background: Recent developments in neuroimaging have advanced the understanding of biological mechanisms underlying schizophrenia. However, neuroimaging correlates of treatment-resistant schizophrenia (TRS) and superior effects of clozapine on TRS remain unclear.

Methods: Systematic search was performed to identify neuroimaging characteristics unique to TRS and ultra-resistant schizophrenia (i.e. clozapine-resistant [URS]), and clozapine's efficacy in TRS using Embase, Medline, and PsychInfo. Search terms included (schizophreni*) and (resistan* OR refractory OR clozapine) and (ASL OR CT OR DTI OR FMRI OR MRI OR MRS OR NIRS OR PET OR SPECT).

Results: 25 neuroimaging studies have investigated TRS and effects of clozapine. Only 5 studies have compared TRS and non-TRS, collectively providing no replicated neuroimaging finding specific to TRS. Studies comparing TRS and healthy controls suggest that hypometabolism in the prefrontal cortex, hypermetabolism in the basal ganglia, and structural anomalies in the corpus callosum contribute to TRS. Clozapine may increase prefrontal hypoactivation in TRS although this was not related to clinical improvement; in contrast, evidence has suggested a link between clozapine efficacy and decreased metabolism in the basal ganglia and thalamus.

Conclusion: Existing literature does not elucidate neuroimaging correlates specific to TRS or URS, which, if present, might also shed light on clozapine's efficacy in TRS. This said, leads from other lines of investigation, including the glutamatergic system can prove useful in guiding future neuroimaging studies focused on, in particular, the frontocortical-basal ganglia-thalamic circuits. Critical to the success of this work will be precise subtyping of study subjects based on treatment response/nonresponse and the use of multimodal neuroimaging.

Keywords: Clozapine; Glutamate; Neuroimaging; Schizophrenia; Treatment-resistance.

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Figures

Figure 1
Figure 1
Flowchart illustrating literature search and exclusion process (PRISMA diagram). Abbreviations: ASL = arterial spin labeling, AVH = auditory verbal hallucinations, CLZ = clozapine, CT = computed tomography, DTI = diffusion tensor imaging, MRS = magnetic resonance imaging, fMRI = functional MRI, MRS = magnetic resonance spectroscopy, PET = positron emission tomography, SPECT = single photon emission tomography, TRS = treatment resistant schizophrenia.
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