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.
| Original language | English |
|---|---|
| Pages (from-to) | 164-175 |
| Number of pages | 12 |
| Journal | Schizophrenia Research |
| Volume | 164 |
| Issue number | 1-3 |
| DOIs | |
| Publication status | Published - 2015 May 1 |
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Keywords
- Clozapine
- Glutamate
- Neuroimaging
- Schizophrenia
- Treatment-resistance
ASJC Scopus subject areas
- Psychiatry and Mental health
- Biological Psychiatry
Cite this
Neuroimaging findings in treatment-resistant schizophrenia : A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia. / Nakajima, Shinichiro; Takeuchi, Hiroyoshi; Plitman, Eric; Fervaha, Gagan; Gerretsen, Philip; Caravaggio, Fernando; Chung, Jun Ku; Iwata, Yusuke; Remington, Gary; Graff-Guerrero, Ariel.
In: Schizophrenia Research, Vol. 164, No. 1-3, 01.05.2015, p. 164-175.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Neuroimaging findings in treatment-resistant schizophrenia
T2 - A systematic review: Lack of neuroimaging correlates of treatment-resistant schizophrenia
AU - Nakajima, Shinichiro
AU - Takeuchi, Hiroyoshi
AU - Plitman, Eric
AU - Fervaha, Gagan
AU - Gerretsen, Philip
AU - Caravaggio, Fernando
AU - Chung, Jun Ku
AU - Iwata, Yusuke
AU - Remington, Gary
AU - Graff-Guerrero, Ariel
PY - 2015/5/1
Y1 - 2015/5/1
N2 - 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.
AB - 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.
KW - Clozapine
KW - Glutamate
KW - Neuroimaging
KW - Schizophrenia
KW - Treatment-resistance
UR - http://www.scopus.com/inward/record.url?scp=84929281198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84929281198&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2015.01.043
DO - 10.1016/j.schres.2015.01.043
M3 - Review article
C2 - 25684554
AN - SCOPUS:84929281198
VL - 164
SP - 164
EP - 175
JO - Schizophrenia Research
JF - Schizophrenia Research
SN - 0920-9964
IS - 1-3
ER -