Cognitive Function and Variability in Antipsychotic Drug–Naive Patients With First-Episode Psychosis

JAMA Psychiatry, Journal Year: 2024, Volume and Issue: 81(5), P. 468 - 468

Published: Feb. 28, 2024

Importance Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset a group level; however, the question heterogeneity cognitive among patients has not been systematically investigated. Objective To provide an updated quantification before receive potentially confounding antipsychotic treatment, investigate variability compared healthy controls. Data Sources In this systematic review meta-analysis, PubMed articles were searched up September 15, 2022. Study Selection Original studies reporting data on drug–naive first-episode (FEP) included. Extraction Synthesis independently extracted by 2 researchers. tasks clustered according 6 domains Measurement Treatment Research Improve Cognition Schizophrenia (MATRICS) Consensus Battery domain executive function. Random-effects model meta-analyses mean differences coefficient variation ratios (CVRs) performed, as well meta-regressions, assessment study quality, publication bias. Main Outcomes Measures The main measure was Hedges g for cognition CVR within-group variability. Results Fifty included analysis total 2625 FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) 2917 controls 26.0 [4.6]; 55% 45% female). all domains, displayed significant (speed processing: = −1.16; 95% CI, −1.35 −0.98; verbal learning: −1.08; −1.28 −0.88; visual −1.05; −1.27 −0.82; working memory: −1.04; −0.73; attention: −1.03; −1.24 reasoning/problem solving: −0.90; −1.12 −0.68; function: −1.07 −0.69). Individuals also exhibited larger across (CVR range, 1.34-1.92). Conclusions Relevance meta-analysis identified initiation large effect sizes. high within suggests need identify those more severe problems who risk worse outcomes could benefit most from remediation.

Language: Английский

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The MR neuroimaging protocol for the Accelerating Medicines Partnership® Schizophrenia Program

Schizophrenia, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 2, 2025

Abstract Neuroimaging with MRI has been a frequent component of studies individuals at clinical high risk (CHR) for developing psychosis, goals understanding potential brain regions and systems impacted in the CHR state identifying prognostic or predictive biomarkers that can enhance our ability to forecast outcomes. To date, most involving are likely not sufficiently powered generate robust generalizable neuroimaging results. Here, we describe prospective, advanced, modern protocol was implemented complex multi-site, multi-vendor environment, as part large-scale Accelerating Medicines Partnership® Schizophrenia Program (AMP® SCZ), including rationale various choices. This includes T1- T2-weighted structural scans, resting-state fMRI, diffusion-weighted imaging collected two time points, approximately 2 months apart. We also present preliminary variance analyses several measures, such signal- contrast-to-noise ratio (SNR/CNR) spatial smoothness, provide quantitative data on relative percentages participant, site, platform (i.e., scanner model) variance. Site-related is generally small (typically <10%). For SNR/CNR measures from fMRI participant largest (as desired; 40–76%). However, diffusion there substantial platform-related (>55%) due differences hardware capabilities different scanners. Also, smoothness large inherent, difficult control, between vendors their acquisitions reconstructions. These results illustrate some factors will need be considered AMP SCZ data, which cohort date. Watch Dr. Harms discuss this article https://vimeo.com/1059777228?share=copy#t=0 .

Language: Английский

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Relations of temporoparietal connectivity with neighborhood social fragmentation in youth at clinical high-risk for psychosis

Schizophrenia Research, Journal Year: 2025, Volume and Issue: 277, P. 151 - 158

Published: March 1, 2025

Language: Английский

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Enabling FAIR data stewardship in complex international multi-site studies: Data Operations for the Accelerating Medicines Partnership® Schizophrenia Program

Schizophrenia, Journal Year: 2025, Volume and Issue: 11(1)

Published: April 3, 2025

Abstract Modern research management, particularly for publicly funded studies, assumes a data governance model in which grantees are considered stewards rather than owners of important sets. Thus, there is an expectation that collected shared as widely possible with the general community. This presents problems complex studies involve sensitive health information. The latter requires balancing participant privacy needs Here, we report on operation ecosystem crafted Accelerating Medicines Partnership® Schizophrenia project, international observational study young individuals at clinical high risk developing psychotic disorder. We review capture systems, dictionaries, organization principles, flow, security, quality control protocols, visualization, monitoring, and dissemination through NIMH Data Archive platform. focus interconnectedness these steps, where our goal to design seamless flow alignment FAIR (Findability, Accessibility, Interoperability, Reusability) principles while local regulatory ethical considerations. process-oriented approach leverages automated pipelines enhance quality, speed, collaboration, underscoring project’s contribution advancing practices involving multisite mental conditions. An feature data’s close-to-real-time assessment (QA) (QC). QA/QC makes it subject redo testing session, well facilitate course corrections prevent repeating errors future acquisition. Watch Dr. Sylvain Bouix discuss his work this article: https://vimeo.com/1025555648 .

Language: Английский

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Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?

Biological Psychiatry, Journal Year: 2021, Volume and Issue: 91(8), P. 709 - 717

Published: Oct. 29, 2021

Large-scale genomic studies of schizophrenia have identified hundreds genetic loci conferring risk to the disorder. This progress offers an important route toward defining biological basis condition and potentially developing new treatments. In this review, we discuss insights from recent genome-wide association study, copy number variant, exome sequencing analyses schizophrenia, together with functional genomics data pre- postnatal brain, in relation synaptic development function. These provide strong support for view that dysfunction within glutamatergic GABAergic (gamma-aminobutyric acidergic) neurons cerebral cortex, hippocampus, other limbic structures is a central component pathophysiology. Implicated genes suggest disturbances connectivity associated susceptibility begin utero but continue throughout development, some alleles disorder through direct effects on function adulthood. model implies novel interventions could include broad preventive approaches aimed at enhancing health during as well more targeted treatments correcting affected adults.

Language: Английский

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Clinical outcomes in individuals at clinical high risk of psychosis who do not transition to psychosis: a meta-analysis

Epidemiology and Psychiatric Sciences, Journal Year: 2022, Volume and Issue: 31

Published: Jan. 1, 2022

Abstract Aims The clinical outcomes of individuals at high risk psychosis (CHR-P) who do not transition to are heterogeneous and inconsistently reported. We aimed comprehensively evaluate longitudinally a wide range in CHR-P developing psychosis. Methods “Preferred Reporting Items for Systematic reviews Meta-Analyses” “Meta-analysis Of Observational Studies Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original longitudinal studies PubMed Web Science databases up 01/11/2021. As primary analysis, we evaluated the following within non-transitioning individuals: (a) change severity attenuated psychotic symptoms (Hedge's g ); (b) negative (c) depressive (d) level functioning (e) frequency remission (at follow-up). secondary compared these those did vs. follow-up. conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity meta-regressions publication bias assessment. was assessed using modified version Newcastle-Ottawa Scale (NOS). Results Twenty-eight were included (2756 individuals, mean age = 20.4, 45.5% females). duration follow-up 30.7 months. Primary analysis: [Hedges’ 1.410, 95% confidence interval (CI) 1.002–1.818]; (Hedges’ 0.683, CI 0.371–0.995); 0.844, 0.371–1.317); 0.776, 0.463–1.089) improved individuals; 48.7% remitted (95% 39.3–58.2%). Secondary 0.706, 0.091–1.322) 0.623, 0.375–0.871) not-transitioning transitioning psychosis, but there no differences or ( p > 0.05). Older associated with higher improvements β 0.225, 0.012); years improvement −0.124, 0.0026); lower proportion Brief Limited Intermittent Psychotic Symptoms frequencies −0.054, 0.0085). There metaregression impact study continent, psychometric instrument used, quality females. NOS scores 4.4 ± 0.9, ranging from 3 6, revealing moderate studies. Conclusions Clinical improve only less than half remit over time. Sustained attention should be provided longer term monitor outcomes.

Language: Английский

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Accelerating Medicines Partnership^® Schizophrenia (AMP^®SCZ): developing tools to enable early intervention in the psychosis high risk state

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(1), P. 42 - 43

Published: Jan. 14, 2023

Schizophrenia is a severe mental illness that presents with pos­itive, negative and cognitive symptoms ranks among the top 15 leading causes of disability worldwide1. Signs risk for developing this can occur months to years before diagnosis. This early period, referred as clinical high (CHR) psychosis state, reflects time during which attenuated psychotic symptoms, marked declines in social role functioning, help-seeking behavior, non-psychotic comorbidity are noted. Intervention CHR state prevent future illness-related dis­ability2. Longitudinal studies individuals show that, at two-year follow-up, approximately 20% transition psychosis3, 41% undergo remission4, but many remainder experience significant problems functioning4. Studies underway establish calculators biomarkers help identify who most likely convert psychosis, more work needed develop tools use mechanistic input stratify populations by predicted outcomes beyond psychosis5. The stage represents unique opportunity interventions guided such tools, focused on reducing conversion improving long-term functional outcomes. Aimed capitalizing opportunity, Accelerating Medicines Partnership® (AMP® SCZ) large international collaboration algorithms using set assessments, multi-modal biomarkers, endpoints be used predict trajectories advance testing pharmacological need. goal accurately remit, an acute episode, or have intermediate feature persistent and/or mood along impairment. will potential serve indicators treatment efficacy persons. AMP SCZ partnership, managed Foundation National Institutes Health (FNIH), brings together breadth scientific regulatory expertise lived from partners: US Institute Mental (NIMH), Food Drug Administration (FDA), European Agency (EMA); private industry (Boehringer Ingelheim; Janssen Research & Development; Otsuka Pharmaceutical Development Commercialization); non-profit patient advocacy organizations (American Psychiatric Association Foundation; Alliance Illness; One Mind; Psychosis Action Alliance); charitable foundation (Wellcome). partnership contribute $117.7 million over 5 ($99.4 NIMH, $7.5 industry, $10.8 organizations) support implementation program. program composed two Networks – Psychosis-Risk Outcomes Network (ProNET) Yale University, Trajectories Predictors Population: Prediction Scientific Global Consortium (PRESCIENT) University Melbourne/Orygen Data Processing, Analysis Coordination Center (DPACC) Harvard Medical School6. ProNET PRESCIENT form harmonized research network individuals: identifying biological markers, endpoints, other measures disease trajectory group. DPACC responsible managing, processing, disseminating, archiving analyzing data, rapidly disseminated made accessible all qualified researchers public within NIMH Archive7. recruit cohort (N=1,977) between ages 12 30 meet criteria based Positive SYmptoms CAARMS Harmonized SIPS (PSYCHS) interview, new psychometric instrument defining associated healthy controls (N=640) across 42 sites 14 countries (US, Canada, UK, Spain, Italy, Switzerland, Netherlands, Germany, Denmark, Australia, Singapore, South Korea, Chile China). participants complete screening, baseline battery follow-up assessments 24 months. Healthy screening subset (approximately per site) month 2, visits. assessed core 2 post-baseline, additional completed timepoints. subjects longitudinally up years. Subjects their first episode (“converted” cases) course study participation continue followed scheduled. Measures include assessments; neurophysiology, neuroimaging, genetics fluid biomarkers; speech facial expression (audio/video recording); digital assessments8. collect active (e.g., daily survey interactions feelings connectedness) passive spent sleeping, number texts phone calls received made; spend green space, home, school, exercising, therapy visits, relationships) automated assessment community functioning global positioning system (GPS) data. Through measures, able assess bio-psycho-social data elucidate affecting could targeted psychosocial interventions. primary endpoint interest 24-month defined threshold PSYCHS. Secondary remission recovery non-conversion/non-remission. Clinical cover multiple domains positive anxiety, symptoms8. biomarker collected analyzed prediction models drawing recent theoretical methodological advances dynamic prediction, probabilistic multimodal modeling). These leverage existing field9 guide selection stratification trials interest. For example, higher relative rest. developed may utility decision making about stepping down (clinical trajectory, response) response incoming information. Some calculators, prioritize less invasive readily available enable community-based settings tolerable subjects. novel generated dataset tested cross-validation approaches designed improve generalizability derived cohorts. By integrating strengths stakeholders, sharing discoveries openly, priming research, aims catalyze knowledge population intervention earliest stages schizophrenia, maximizing patients.

Language: Английский

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Mismatch Negativity in Response to Auditory Deviance and Risk for Future Psychosis in Youth at Clinical High Risk for Psychosis

JAMA Psychiatry, Journal Year: 2022, Volume and Issue: 79(8), P. 780 - 780

Published: June 8, 2022

Importance

Although clinical criteria for identifying youth at risk psychosis have been validated, they are not sufficiently accurate predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals high (CHR-P).

Objective

To examine whether mismatch negativity (MMN) event–related potential amplitude, which is deficient in schizophrenia, reduced young people with the CHR-P syndrome and associated outcomes, accounting effects antipsychotic medication use.

Design, Setting, Participants

MMN data were collected as part multisite case-control North American Prodrome Longitudinal Study (NAPLS-2) from 8 university-based outpatient research programs. Baseline June 2009 through April 2013. Clinical assessed throughout 24 months. Participants healthy controls data. who developed (ie, converters) compared those did develop nonconverters) followed up Analysis took place between December 2019 2021.

Main Outcomes Measures

Electroencephalography was recorded during a passive auditory oddball paradigm. elicited by duration-, pitch-, duration + pitch double-deviant tones measured.

Results

group (n = 580; mean [SD] age, 19.24 [4.39] years) included 247 female (42.6%) control 241; 20.33 [4.74] 114 (47.3%). In group, 450 (77.6%) taking baseline. amplitudes, irrespective deviant type, future converters 77, unmedicated n 54) nonconverters 238, 190) both full sample (d 0.27) subsample 0.33). sample, baseline status interacted type indicating that MMN, single deviants, 0.43). Further, within subsample, deficits most strongly earlier conversion (hazard ratio, 1.40 [95% CI, 1.03-1.90];P .03], persisted over above positive symptom severity.

Conclusions Relevance

This study found amplitude sensitive CHR-P, particularly baseline, although associations modest. While shows limited promise biomarker onset on its own, it contribute novel information multivariate algorithms serve translational neurophysiological target development subgroup at-risk individuals.

Language: Английский

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Transdiagnostic risk of mental disorders in offspring of affected parents: a meta‐analysis of family high‐risk and registry studies

World Psychiatry, Journal Year: 2023, Volume and Issue: 22(3), P. 433 - 448

Published: Sept. 15, 2023

The offspring of parents with mental disorders are at increased risk for developing themselves. to may extend transdiagnostically other than those present in the parents. literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched published up September 2022 retrieve original family high-risk registry studies reporting any type disorder. random-effects meta-analyses relative (risk ratio, RR) absolute (lifetime, age assessment) disorders, defined according ICD or DSM. Cumulative incidence by was determined using meta-analytic Kaplan-Meier curves. measured heterogeneity I2 statistic, bias Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed impact study design (family vs. registry) specific transdiagnostic risks. Transdiagnosticity appraised TRANSD criteria. identified 211 independent that reported data 3,172,115 psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, borderline personality 20,428,575 control offspring. RR lifetime disorder were 3.0 55% anxiety disorders; 2.6 17% psychosis; 2.1 bipolar disorder; 1.9 51% depressive 1.5 38% use disorders. offspring's same diagnosed their parent 8.4 32% attention-deficit/hyperactivity 5.8 8% 5.1 5% 2.8 9% 2.3 14% 1% eating 2.2 31% There 37 significant associations between parental different psychosis, disorder, onset emerged 16, 5 6 years, cumulated 3%, 19% 24% 18; 8%, 36% 46% 28. Heterogeneity ranged from 0 0.98, 96% high bias. restricted prospective confirmed pattern findings similar RR, greater risks compared all types. This demonstrates global, level affected have strongly elevated as well parent. suggest range should be considered candidates primary prevention.

Language: Английский

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Normative Modeling of Brain Morphometry in Clinical High Risk for Psychosis

JAMA Psychiatry, Journal Year: 2023, Volume and Issue: 81(1), P. 77 - 77

Published: Oct. 11, 2023

The lack of robust neuroanatomical markers psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in measures individuals at may be nested within the range observed healthy individuals.

Language: Английский

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