Evidence map›Paper›PMID 25684554›Full record

SynthesisSchizophrenia research2015

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

Shinichiro Nakajima, Hiroyoshi Takeuchi, Eric Plitman, Gagan Fervaha, Philip Gerretsen, Fernando Caravaggio, Jun Ku Chung, Yusuke Iwata, Gary Remington, Ariel Graff-Guerrero

Abstract readSystematic Review
In one paragraph

Synthesis in Schizophrenia research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 4 pooled it
5.9field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 4 syntheses or guidelines pooled it, 87 citations in OpenAlex.

  1. Pooled it
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  6. Review
  7. Article
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  11. Distinct structural deficits in treatment-resistant schizophrenia and their putative neurotransmitter basis: a source-based morphometry analysis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
    Article
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  19. Recent Advances and Future Directions in Brain MR Imaging Studies in Schizophrenia: Toward Elucidating Brain Pathology and Developing Clinical Tools.Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine · 2022
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 2 countries.

Shinichiro NakajimaMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. Electronic address: shinichiro_nakajima@hotmail.com.
Hiroyoshi TakeuchiDepartment of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan; Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: hirotak@dk9.so-net.ne.jp.
Eric PlitmanMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: plitmaneric@gmail.com.
Gagan FervahaSchizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: gagan.fervaha@camh.ca.
Philip GerretsenMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: philgerretsen@yahoo.com.
Fernando CaravaggioMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: fernando.caravaggio@gmail.com.
Jun Ku ChungMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Institute of Medical Science, University of Toronto, Toronto, Canada. Electronic address: junku.chung@mail.utoronto.ca.
Yusuke IwataMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo, Japan. Electronic address: yusuke.iwata2010@gmail.com.
Gary RemingtonDepartment of Psychiatry, University of Toronto, Toronto, Canada; Schizophrenia Division, Complex Mental Illness Program, Centre for Addiction and Mental Health, Toronto, Canada; Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: gary.remington@camh.ca.
Ariel Graff-GuerreroMultimodal Imaging Group - Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, Canada. Electronic address: ariel_graff@yahoo.com.mx.
Centre for Addiction and Mental Health · CAUniversity of Toronto · CAKeio University · JP

Funding

Optimal Dosing of Antipsychotic Drugs in Late LifeR01MH084886 · NIMH · CENTRE FOR ADDICTION AND MENTAL HEALTH · PI MAMO, DAVID · 2010 to 2014
$761k
Canadian Institutes of Health ResearchNIMH NIH HHS R01 MH084886
6 · The paper itself

Abstract

backgroundRecent 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.

methodsSystematic 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).

results25 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.

conclusionExisting 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.

Indexed as

NeuroimagingAntipsychotic AgentsDrug ResistanceHumansSchizophreniaAntipsychotic AgentsClozapineGlutamateNeuroimagingSchizophreniaTreatment-resistance

Identifiers

PMID25684554
PMCPMC4409508
OpenAlexW208517808

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.