2026 ECNP Congress

PS02-2236

Parkinsonism and psychopathology severity in real-world outpatients with schizophrenia: a PRISM analysis

Joaquín Galvañ — J.D. Lopez-Morinigo, G. Salazar de Pablo, M. Sepúlveda, J.L. Ayuso-Mateos, N. Van der Wee, B. Penninx, M. Kas, C. Arango, C. Díaz-Caneja · Institute of Psychiatry and Mental Health Hospital General Universitario Gregorio Marañón, Department of Child and Adolescent Psychiatry, Madrid, Spain

2026 ECNP Congress

Background

Extrapyramidal symptoms have been recognised as illness-related features of schizophrenia, beyond merely medication-induced effects [1-3]. Among them, parkinsonism is the most prevalent subtype and has been linked to poorer clinical outcomes [2-3]. Yet, the prevalence and clinical correlates of parkinsonism in clinically stabilised, community-dwelling outpatients with schizophrenia receiving antipsychotic treatment remain insufficiently characterised. We aimed to examine the prevalence of parkinsonism and its associations with psychopathology and functioning severity, together with relevant demographic and pharmacological correlates, in real-world outpatients with schizophrenia.

Methods

Data were drawn from the PRISM project [4-5], a European-funded, cross-sectional, naturalistic study conducted across the Netherlands and Spain between 2017–2019 (PRISM-1) and 2022–2023 (PRISM-2). Patients aged 18–45 years with a DSM-IV diagnosis of schizophrenia were included if clinically stable on antipsychotic medication for ≥8 weeks and excluded if scoring >22 on the PANSS-Positive subscale. Parkinsonism was assessed with the Extrapyramidal Symptoms Rating Scale (ESRS), psychopathology with the PANSS, social functioning with the SFS, and loneliness with the De Jong Gierveld Scale. Quantitative variables were summarised as mean±SD and compared using Student’s t-tests, whereas categorical variables were expressed as percentages and compared using χ² tests. Associations were examined through Spearman’s correlations and multivariable linear regression models adjusted for cohort (PRISM-1/2), age, sex, ethnicity (White/“non-White”), cumulative antipsychotic dose (chlorpromazine equivalents), and concomitant psychotropic medication (yes/no).

Results

Ninety patients were included, mean age 31.53±6.64 years, 36.7% female, 27.8% of “non-White” ethnicity. Most patients received second-generation antipsychotics (89.3%), in monotherapy regime (73.5%), and oral route (63.3%)—most used antipsychotics were aripiprazole (n=37) and clozapine (n=20). Concomitant psychotropic medication was used by 25.6% of participants. Overall, 51.5% of participants presented parkinsonism (ESRS≥1), with a higher prevalence among “non-White” ethnicity (80% vs. 40%, p<0.001), unrelated to sex or age (all p>0.05). Parkinsonism presence did not differ according to antipsychotic exposure, regime, route, generation, or concomitant psychotropic medication (all p>0.05). Parkinsonism severity was correlated with positive (PANSS-P: rₛ=0.228, 95% CI [0.016-0.420], p=0.031), negative (PANSS-N: rₛ=0.278, 95%CI [0.069-0.463], p=0.008), general (PANSS-G: rₛ=0.210, 95%CI [-0.003-0.405], p=0.047) and total (PANSS-T: rₛ=0.283, 95 %CI [0.074-0.468], p=0.007) symptoms severity, remaining significantly associated with negative (PANSS-N: β=0.352, 95%CI [0.941-3.781], p=0.001) and total (PANSS-T: β=0.325, 95%CI [1.517-7.340], p=0.003) symptoms severity in fully adjusted regression models. No significant associations were found between parkinsonism severity and measures of social functioning or loneliness (all p>0.05).

Conclusions

We observed a high prevalence of parkinsonism in clinically stabilised, community-dwelling outpatients with chronic schizophrenia receiving antipsychotics, higher among participants of “non-White” ethnicity, potentially reflecting underlying genetic susceptibility. Parkinsonism severity was associated with psychopathology—particularly negative symptoms—but not with antipsychotic exposure nor measures of social functioning or loneliness. This association supports the hypothesis that parkinsonism represents an illness-intrinsic feature of schizophrenia rather than solely a medication-induced effect [1-3] and may reflect shared disturbances in dopaminergic cortical–subcortical circuits [1-3]. Incorporating neurological assessments into routine psychiatric evaluations may provide an accesible clinical marker to monitor illness trajectories and guide treatment decisions [1-3]. Future mechanistic studies are warranted to clarify causal relationships and to determine whether targeting parkinsonism may modify clinical outcomes in schizophrenia.

References

  1. Walther S, Van Harten PN, Waddington JL, Cuesta MJ, Peralta V, Dupin L, et al. Movement disorder and sensorimotor abnormalities in schizophrenia and other psychoses - European consensus on assessment and perspectives. Eur Neuropsychopharmacol. 2020 Sep;38:25–39. doi:10.1016/j.euroneuro.2020.07.00[3
  2. Pieters LE, Nadesalingam N, Walther S, van Harten PN. A systematic review of the prognostic value of motor abnormalities on clinical outcome in psychosis. Neurosci Biobehav Rev. 2022 Jan 1;132:691–705. doi:10.1016/j.neubiorev.2021.11.027[
  3. Galvañ J, Suárez-Campayo J, Ayora M, Gil S, Winter-van Rossum I, Berger G, et al. Extrapyramidal symptoms as early clinical predictors in first-episode schizophrenia and schizophreniform disorder: findings from the OPTiMiSE trial. Eur Neuropsychopharmacol. 2025 Sep;98:35–45. doi:10.1016/j.euroneuro.2025.06.007
  4. Kas MJ, Penninx B, Sommer B, Serretti A, Arango C, Marston H. A quantitative approach to neuropsychiatry: The why and the how. Neurosci Biobehav Rev. 2019 Feb;97:3–9. doi:10.1016/j.neubiorev.2017.12.008
  5. Bilderbeck AC, Penninx BWJH, Arango C, Van Der Wee N, Kahn R, Winter-van Rossum I, et al. Overview of the clinical implementation of a study exploring social withdrawal in patients with schizophrenia and Alzheimer’s disease. Neurosci Biobehav Rev. 2019 Feb;97:87–93. doi:10.1016/j.neubiorev.2018.06.019