Evidence map›Paper›PMID 35435461›Full record

ArticlePsychopharmacology2022

Changes in corticostriatal connectivity and striatal tissue iron associated with efficacy of clozapine for treatment‑resistant schizophrenia.

Annie Blazer, K N Roy Chengappa, William Foran, Ashley C Parr, Charles E Kahn, Beatriz Luna, Deepak K Sarpal

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychopharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 2 pooled it
1.9field-weighted citation impact, top 15% 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

18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

Annie BlazerDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
K N Roy ChengappaDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
William ForanDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Ashley C ParrDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Charles E KahnDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Beatriz LunaDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA.
Deepak K SarpalDepartment of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA, 15213, USA. sarpaldk@upmc.edu.
University of Pittsburgh · US

Funding

Neural Biomarkers of Clozapine ResponseK23MH110661 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SARPAL, DEEPAK K · 2016 to 2019
$725k
NIMH NIH HHS K23 MH110661NIMH NIH HHS K23MH110661
6 · The paper itself

Abstract

rationaleThough numerous studies demonstrate the superiority of clozapine (CLZ) for treatment of persistent psychotic symptoms that are characteristic of treatment-refractory schizophrenia (TRS), what remains unknown are the neural and molecular mechanisms underlying CLZ's efficacy. Recent work implicates increased corticostriatal functional connectivity as a marker of response to non-CLZ, dopamine (DA) D2-receptor blocking antipsychotic drugs. However, it is undetermined whether this connectivity finding also relates to CLZ's unique efficacy, or if response to CLZ is associated with changes in striatal DA functioning.

objectiveIn a cohort of 22 individuals with TRS, we examined response to CLZ in relation to the following: (1) change in corticostriatal functional connectivity; and (2) change in a magnetic resonance-based measure of striatal tissue iron (R2'), which demonstrates utility as a proxy measure for elements of DA functioning.

methodsParticipants underwent scanning while starting CLZ and after 12 weeks of CLZ treatment. We used both cortical and striatal regions of interest to examine changes in corticostriatal interactions and striatal R2' in relation to CLZ response (% reduction of psychotic symptoms).

resultsWe first found that response to CLZ was associated with an increase in corticostriatal connectivity between the dorsal caudate and regions of the frontoparietal network (P < 0.05, corrected). Secondly, we observed no significant changes in striatal R2' across CLZ treatment.

conclusionOverall, these results indicate that changes in corticostriatal networks without gross shifts in striatal DA functioning underlies CLZ response. Our results provide novel mechanistic insight into response to CLZ treatment.

Indexed as

Antipsychotic AgentsClozapineSchizophreniaHumansIronSchizophrenia, Treatment-ResistantAntipsychotic AgentsClozapineIronAntipsychotic treatmentClozapineFunctional connectivityR2’SchizophreniaStriatumTreatment-resistant schizophreniaTreatment response

Identifiers

PMID35435461
PMCPMC9013738
OpenAlexW4223968697

What OpenQuestion holds

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Registered trials

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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.