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. 2024 Oct 15;54(13):1-12.
doi: 10.1017/S0033291724001776. Online ahead of print.

Neurodevelopmental predictors of treatment response in schizophrenia and bipolar disorder

Anton Iftimovici  1   2   3   4 , Emma Krebs  1 , William Dalfin  1 , Adrien Legrand  3 , Linda Scoriels  1   2 , Gilles Martinez  3 , Narjes Bendjemaa  3 , Edouard Duchesnay  4 , Boris Chaumette  1   2   3   5 , Marie-Odile Krebs  1   2   3
Affiliations

Neurodevelopmental predictors of treatment response in schizophrenia and bipolar disorder

Anton Iftimovici et al. Psychol Med. .

Abstract

Background: Treatment resistance is a major challenge in psychiatric disorders. Early detection of potential future resistance would improve prognosis by reducing the delay to appropriate treatment adjustment and recovery. Here, we sought to determine whether neurodevelopmental markers can predict therapeutic response.

Methods: Healthy controls (N = 236), patients with schizophrenia (N = 280) or bipolar disorder (N = 78) with a known therapeutic outcome, were retrospectively included. Age, sex, education, early developmental abnormalities (obstetric complications, height, weight, and head circumference at birth, hyperactivity, dyslexia, epilepsy, enuresis, encopresis), neurological soft signs (NSS), and ages at first subjective impairment, clinical symptoms, treatment, and hospitalization, were recorded. A supervised algorithm leveraged NSS and age at first clinical signs to classify between resistance and response in schizophrenia.

Results: Developmental abnormalities were more frequent in schizophrenia and bipolar disorder than in controls. NSS significantly differed between controls, responsive, and resistant participants with schizophrenia (5.5 ± 3.0, 7.0 ± 4.0, 15.0 ± 6.0 respectively, p = 3 × 10-10) and bipolar disorder (5.5 ± 3.0, 8.3 ± 3.0, 12.5 ± 6.0 respectively, p < 1 × 10-10). In schizophrenia, but not in bipolar disorder, age at first subjective impairment was three years lower, and age at first clinical signs two years lower, in resistant than responsive subjects (p = 2 × 10-4 and p = 9 × 10-3, respectively). Age at first clinical signs and NSS accurately predicted treatment response in schizophrenia (area-under-curve: 77 ± 8%, p = 1 × 10-14).

Conclusions: Neurodevelopmental features such as NSS and age of clinical onset provide a means to identify patients who may require rapid treatment adaptation.

Keywords: age at onset of disease; bipolar disorder; neurodevelopment; neurological soft signs; schizophrenia; treatment response.

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Conflict of interest statement

The authors report no conflict of interest in relation to this work.

Figures

Figure 1.
Figure 1.
Effect-size of the difference in neurological soft signs between healthy controls, schizophrenia, and bipolar disorder. Bootstrapped 95% confidence interval of the effect-size between: (a) controls and schizophrenia or bipolar disorder (d = 1.13, p < 1 × 10−10 and d = 1.00, FDR-adjusted p < 1 × 10−10 respectively), (b) schizophrenia and bipolar disorder (d = 0.35, FDR-adjusted p = 0.006), (c) controls and schizophrenia or bipolar disorder without treatment (d = 1.88, p < 1 × 10−10 and d = 0.98, p = 2 × 10−5 respectively), and (d) schizophrenia and bipolar disorder without treatment (d = 0.56, p = 0.06).
Figure 2.
Figure 2.
Bootstrapped 95% confidence interval of the effect-size of the difference for neurological soft signs and age at first clinical signs in (a) schizophrenia (d = 0.82, p < 1 × 10−10 and d = −0.35, p = 9 × 10−3 respectively), and (b) in bipolar disorder (d = 0.48, p = 0.01 and d = −0.3, p = 0.20, respectively).
Figure 3.
Figure 3.
Prediction of treatment response based on age at first subjective symptoms and the three domains of neurological soft signs: motor coordination, motor integration, and sensory integration. (a) ROC curve and area-under-the-curve (AUC). (b) Distribution of responsive and resistant subjects with schizophrenia depending on NSS total (sum of the 3 dimensions) and age at onset of first clinical signs.
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References

    1. Ajnakina, O., Das, T., Lally, J., Di Forti, M., Pariante, C. M., Marques, T. R., … Dazzan, P. (2021). Structural covariance of cortical gyrification at illness onset in treatment resistance: A longitudinal study of first-episode psychoses. Schizophrenia Bulletin, 47(6), 1729–1739. doi: 10.1093/schbul/sbab035 - DOI - PMC - PubMed
    1. Arango, C., Díaz-Caneja, C. M., McGorry, P. D., Rapoport, J., Sommer, I. E., Vorstman, J. A., … Carpenter, W. (2018). Preventive strategies for mental health. The Lancet Psychiatry, 5(7), 591–604. doi: 10.1016/S2215-0366(18)30057-9 - DOI - PubMed
    1. Bachmann, C. J., Aagaard, L., Bernardo, M., Brandt, L., Cartabia, M., Clavenna, A., … Taylor, D. (2017). International trends in clozapine use: A study in 17 countries. Acta Psychiatrica Scandinavica, 136(1), 37–51. doi: 10.1111/acps.12742 - DOI - PubMed
    1. Bachmann, S., & Schröder, J. (2018). Neurological soft signs in schizophrenia: An update on the state- versus trait-perspective. Frontiers in Psychiatry, 8, 272. doi: 10.3389/fpsyt.2017.00272 - DOI - PMC - PubMed
    1. Bora, E., Akgül, Ö, Ceylan, D., & Özerdem, A. (2018). Neurological soft signs in bipolar disorder in comparison to healthy controls and schizophrenia: A meta-analysis. European Neuropsychopharmacology, 28(11), 1185–1193. doi: 10.1016/j.euroneuro.2018.08.006 - DOI - PubMed

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