Trial reportNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Differentiating the effect of antipsychotic medication and illness on brain volume reductions in first-episode psychosis: A Longitudinal, Randomised, Triple-blind, Placebo-controlled MRI Study.
Trial report in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 78 citations in OpenAlex.
- Psychotropic medications and their interactions with subcortical brain volume in bipolar disorder: An ENIGMA mega-analysis.Molecular psychiatry · 2026Pooled it
- Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis.Schizophrenia research · 2024Pooled it
- Antipsychotics cause reversible structural brain changes within one week.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Trial
- Network-Based Spreading of Gray Matter Changes Across Different Stages of Psychosis.JAMA psychiatry · 2023Trial
- Effects of antipsychotic medication on functional connectivity in major depressive disorder with psychotic features.Molecular psychiatry · 2023Trial
- Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial.Translational psychiatry · 2023Trial
- Psychosocial Interventions, Recovery, and Mediating Mechanisms in Schizophrenia-Spectrum Disorders: A Systematic Review and Meta-Analysis of Longitudinal Studies.Brain sciences · 2026Review
- Widespread synaptic density loss in schizophrenia follows molecular and network architecture.Molecular psychiatry · 2026Article
- Data-driven schizophrenia subtyping via brain atrophy trajectories and functional connectivity.Translational psychiatry · 2026Article
- Novel epigenetic loci identified from an epigenome-wide association study underlying brain structural changes in bipolar disorder.Psychological medicine · 2026Article
- Brain Age Disparities in Psychosis Across DSM Diagnoses and B-SNIP Biotypes.Schizophrenia bulletin · 2026Article
- Helping people to discontinue antipsychotics: if, when and how.Schizophrenia (Heidelberg, Germany) · 2025Review
- Substance-Specific Treatment Responses and Resistance Patterns in Induced Psychoses: A Scoping Review of Antipsychotic Efficacy.Healthcare (Basel, Switzerland) · 2025Review
- Subtyping schizophrenia via machine learning by using structural neuroimaging.Translational psychiatry · 2025Review
- Neuroimaging endophenotypes reveal underlying mechanisms and genetic factors contributing to progression and development of four brain disorders.Nature biomedical engineering · 2025Article
- Subcortical brain abnormalities and cognitive function in individuals with psychosis and their unaffected relatives: A normative modeling approach.Schizophrenia research · 2025Article
- Long-acting injectable antipsychotics for patients with first-episode and early-phase schizophrenia: still not considered often enough.CNS spectrums · 2025Review
- Medications for psychosis in people with schizophrenia: what happens if you take them and what happens if you don't?CNS spectrums · 2025Review
- Molecular, physiological and functional features underlying antipsychotic medication use related cortical thinning.Translational psychiatry · 2025Article
- Brain Markers of Resilience to Psychosis in High-Risk Individuals: A Systematic Review and Label-Based Meta-Analysis of Multimodal MRI Studies.Brain sciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Changes in brain volume are a common finding in Magnetic Resonance Imaging (MRI) studies of people with psychosis and numerous longitudinal studies suggest that volume deficits progress with illness duration. However, a major unresolved question concerns whether these changes are driven by the underlying illness or represent iatrogenic effects of antipsychotic medication. In this study, 62 antipsychotic-naïve patients with first-episode psychosis (FEP) received either a second-generation antipsychotic (risperidone or paliperidone) or a placebo pill over a treatment period of 6 months. Both FEP groups received intensive psychosocial therapy. A healthy control group (n = 27) was also recruited. Structural MRI scans were obtained at baseline, 3 months and 12 months. Our primary aim was to differentiate illness-related brain volume changes from medication-related changes within the first 3 months of treatment. We secondarily investigated long-term effects at the 12-month timepoint. From baseline to 3 months, we observed a significant group x time interaction in the pallidum (p < 0.05 FWE-corrected), such that patients receiving antipsychotic medication showed increased volume, patients on placebo showed decreased volume, and healthy controls showed no change. Across the entire patient sample, a greater increase in pallidal grey matter volume over 3 months was associated with a greater reduction in symptom severity. Our findings indicate that psychotic illness and antipsychotic exposure exert distinct and spatially distributed effects on brain volume. Our results align with prior work in suggesting that the therapeutic efficacy of antipsychotic medications may be primarily mediated through their effects on the basal ganglia.
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Registered trials
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.