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. 2022 Mar 11;8(1):20.
doi: 10.1038/s41537-021-00196-7.

Cortical thinning over two years after first-episode psychosis depends on age of onset

Laura Pina-Camacho #  1   2 , Kenia Martinez #  3 , Covadonga M Diaz-Caneja  3 , Gisela Mezquida  4 , Manuel J Cuesta  5 , Carmen Moreno  3 , Silvia Amoretti  4 , Ana González-Pinto  6 , Celso Arango  3 , Eduard Vieta  7 , Josefina Castro-Fornieles  8 , Antonio Lobo  9 , David Fraguas  10 , Miguel Bernardo  4 , Joost Janssen #  3 , Mara Parellada #  3 ; PEPs Group
Collaborators, Affiliations

Cortical thinning over two years after first-episode psychosis depends on age of onset

Laura Pina-Camacho et al. Schizophrenia (Heidelb). .

Abstract

First-episode psychosis (FEP) patients show structural brain abnormalities at the first episode. Whether the cortical changes that follow a FEP are progressive and whether age at onset modulates these changes remains unclear. This is a multicenter MRI study in a deeply phenotyped sample of 74 FEP patients with a wide age range at onset (15-35 years) and 64 neurotypical healthy controls (HC). All participants underwent two MRI scans with a 2-year follow-up interval. We computed the longitudinal percentage of change (PC) for cortical thickness (CT), surface area (CSA) and volume (CV) for frontal, temporal, parietal and occipital lobes. We used general linear models to assess group differences in PC as a function of age at FEP. We conducted post-hoc analyses for metrics where PC differed as a function of age at onset. We found a significant age-by-diagnosis interaction effect for PC of temporal lobe CT (d = 0.54; p = 002). In a post-hoc-analysis, adolescent-onset (≤19 y) FEP showed more severe longitudinal cortical thinning in the temporal lobe than adolescent HC. We did not find this difference in adult-onset FEP compared to adult HC. Our study suggests that, in individuals with psychosis, CT changes that follow the FEP are dependent on the age at first episode, with those with an earlier onset showing more pronounced cortical thinning in the temporal lobe.

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Conflict of interest statement

L.P-C. has received grant support from Fundación Alicia Koplowitz and Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and has received honoraria or grants unrelated to the present work from Rubió, Rovi and Janssen. C.D-C. holds a Juan Rodés grant from Instituto de Salud Carlos III (JR19/00024), Spanish Ministry of Science and Innovation, and has received honoraria from AbbVie, Sanofi, and Exeltis. C.M. has received grants and served as consultant or advisor from European Union Funds, Fundación Alicia Koplowitz, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, CIBERSAM, Janssen, Angelini, Servier, Nuvelution, Otsuka, Lundbeck and Esteve. E.V. has received grants and served as consultant, advisor or CME speaker unrelated to the present work for the following entities: AB-Biotics, Abbott, Allergan, Angelini, Dainippon Sumitomo Pharma, Ferrer, Gedeon Richter, Janssen, Lundbeck, Otsuka, Sage, Sanofi-Aventis, Sunovion, and Takeda. C.A. has been a consultant, to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion, and Takeda. D.F. has been a consultant to and/or receiving fees from Angelini, Eisai, IE4Lab, Janssen, Lundbeck, and Otsuka and has received grant support from Fundación Alicia Koplowitz and Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. M.B. has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. M.P. has received grants and served as consultant, advisor or CME speaker unrelated to the present work for the following entities: Servier, Exceltis, Lundbeck, Fundación Alicia Koplowitz, Fundación Familia Alonso, Ministry of Health, and Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation. The remaining authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Age-by-diagnosis interaction effect on PC of temporal lobe CT.
For FEP and HC, PC values < 0 indicate cortical thinning (CT decrease) over follow-up.; PC values > 0 indicate thickening (CT increase) over follow-up. Abbreviations: CT cortical thickness, FEP first episode psychosis, HC healthy controls, PC percentage of change.
Fig. 2
Fig. 2. Age-by-diagnosis interaction effect on PC of temporal lobe CSA/CV and on PC of frontal, parietal and occipital CT/CSA/CV.
A Age-by-diagnosis interaction effect on PC of temporal lobe CSA (left side) and CV (right side). For FEP and HC, PC values < 0 indicate decrease (in surface area or volume) over follow-up.; PC values > 0 indicate increase (in surface area or volume) over follow-up. B Cohen’s d, p values and confidence intervals (CI, 95%) for the age-by-diagnosis interaction effect on PC of frontal, parietal and occipital CT/CSA/CV. Abbreviations: CSA cortical surface area, CV cortical volume, FEP first episode psychosis, HC healthy controls, PC percentage of change.
Fig. 3
Fig. 3. Temporal lobe CT for adolescent and adult FEP and HC.
A Temporal lobe CT for adolescent and adult FEP and HC at T1 and T2. Dashed brackets: GLMs (FEP vs. HC comparisons, at T1 and T2). Solid brackets: Repeated measures mixed models (intragroup T2–T1 change of temporal lobe CT). B Association between temporal lobe CT at T1 and PC of temporal lobe CT, for adolescent FEP, adult FEP, and whole FEP samples. Pearson’s correlations, p values and confidence intervals (95%) shown. “x” axis: CT values > 0 indicate thicker cortex in FEP relative to HC, CT values < 0 indicate thinner cortex. “y axis”: PC values < 0 indicate cortical thinning; PC values > 0 indicate cortical thickening over follow-up. T1: baseline scan; T2: follow-up scan. CT cortical thickness, FEP first-episode psychosis, HC healthy controls, PC percentage of change.
Fig. 4
Fig. 4. Association between PC of temporal lobe CT and symptom change scores in FEP clusters 1 and 2.
A Association between PC of temporal lobe CT (at lobar and regional level) and PANSS positive, negative, and total change scores, in FEP clusters 1 and 2. In the correlation matrix, only significant relationships (p < 0.05) are color-coded according to the color bar on the bottom. B Association between PC of temporal lobe CT and PANSS negative change score, in FEP clusters 1 and 2. Pearson’s correlations, p values and confidence intervals (95%) shown for FEP clusters 1 and 2. “x axis”: PANSS change scores < 0 indicate symptom improvement, PANSS change scores > 0 indicate symptom worsening over follow-up. “y axis”: PC values < 0 indicate cortical thinning; PC values > 0 indicate cortical thickening over follow-up. Abbreviations: CT cortical thickness, FEP first-episode psychosis, PANSS positive and negative syndrome scale, PC percentage of change.
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References

    1. Kahn RS, Sommer IE. The neurobiology and treatment of first-episode schizophrenia. Mol. Psychiatry. 2015;20:84–97. doi: 10.1038/mp.2014.66. - DOI - PMC - PubMed
    1. Mechelli A, et al. Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Arch. Gen. Psychiatry. 2011;68:489–495. doi: 10.1001/archgenpsychiatry.2011.42. - DOI - PubMed
    1. Arango C, Kahn R. Progressive brain changes in schizophrenia. Schizophr. Bull. 2008;34:310–311. doi: 10.1093/schbul/sbm166. - DOI - PMC - PubMed
    1. Olabi B, et al. Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biol. Psychiatry. 2011;70:88–96. doi: 10.1016/j.biopsych.2011.01.032. - DOI - PubMed
    1. Haukvik UK, et al. No progressive brain changes during a 1-year follow-up of patients with first-episode psychosis. Psychol. Med. 2016;46:589–598. doi: 10.1017/S003329171500210X. - DOI - PubMed