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. 2025 Jul 22:55:e209.
doi: 10.1017/S0033291725100974.

Obstetric complications, cortical gyrification, and cognition in first-episode psychosis

Ana Costas-Carrera  1   2 , Norma Verdolini  3 , Gisela Mezquida  4   5   6   7 , Maria Florencia Forte  7   8 , Joost Janssen  6   9 , Clemente Garcia-Rizo  2   5   6   7 , Anabel Martinez-Aran  6   7   8 , Pablo Andres-Camazon  6   9 , Ana Maria Sánchez-Torres  10   11   12 , Daniel Berge  6   12   13   14 , Elena de la Serna  6   7   15 , Rafael Penades  2   5   6   7 , Isabel Valli  16   17 , Silvia Amoretti  6   18 ; PEPs Group
Affiliations

Obstetric complications, cortical gyrification, and cognition in first-episode psychosis

Ana Costas-Carrera et al. Psychol Med. .

Abstract

Background: Obstetric complications (OCs) are associated with cognitive and brain abnormalities observed in patients with schizophrenia. Gyrification, a measure of cortical integrity sensitive to events occurring during the prenatal and perinatal periods, is also altered in first-episode psychosis (FEP). We examined the relationship between OCs and gyrification in FEP, as well as whether gyrification mediates the relationship between OCs and cognition.

Methods: We examined differences in the Local Gyrification Index (LGI) for the frontal, parietal, temporal, occipital, and cingulate cortices between 139 FEP patients and 125 healthy controls (HCs). Regression analyses explored whether OCs and diagnosis interact to explain LGI variation. Parametric mediation analyses were conducted to assess the effect of LGI on the relationship between OCs and cognition for FEP and HC.

Results: Significant LGI differences were observed between FEP patients and HC in the left parietal and bilateral cingulate and occipital cortices. There was a significant interaction between OCs and diagnosis on the left cingulate cortex (LCC) that was specific to males (p = 0.04) and was driven by gestational rather than intrauterine OCs.In HCs, OCs had a direct effect on working memory (WM) (p = 0.048) in the mediation analysis, whereas in FEP, we observed no significant effect of OCs on either verbal or WM.

Conclusions: OCs interact with diagnosis to predict LCC gyrification, such that males with FEP exposed to OCs exhibit the lowest LGI. OCs influence WM, and LCC gyrification may mediate this relation only in HC, suggesting a differential neurodevelopmental process in psychosis.

Keywords: cognition; cortical folding; delivery; epiphenomena; first-episode psychosis; gyrification; intrauterine period; magnetic resonance imaging; obstetric complications; schizophrenia; verbal memory; working memory.

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Conflict of interest statement

NV has received financial support for CME activities and travel funds from the following entities: Angelini, Janssen-Cilag, Lundbeck, and Otsuka. CGR has received grants from/or served as a consultant, advisor, or speaker for the following entities: Adamed, Angelini, Casen-Recordati, Janssen-Cilag, Lunbeck, and Newron. IB has received honoraria or travel support from Otsuka-Lundbeck and Angelini. EV has received grants and served as a consultant, advisor, or CME speaker for the following entities: AB-Biotics, AbbVie, Adamed, Alcediag, Angelini, Biogen, Beckley-Psytech, Biohaven, Boehringer-Ingelheim, Celon Pharma, Compass, Dainippon Sumitomo Pharma, Esteve, Ethypharm, Ferrer, Gedeon Richter, GH Research, Glaxo-Smith Kline, HMNC, Idorsia, Johnson & Johnson, Lundbeck, Luye Pharma, Medincell, Merck, Newron, Novartis, Orion Corporation, Organon, Otsuka, Roche, Rovi, Sage, Sanofi-Aventis, Sunovion, Takeda, Teva, and Viatris, outside the submitted work. RRJ has been a consultant for, spoken in activities of, or received grants from JanssenCilag, Lundbeck, Otsuka, Pfizer, Ferrer, Juste, Takeda, Exeltis, Casen-Recordati, Angelini, and Rovi. AI has received research support from or served as a speaker or advisor for JanssenCilag, Lundbeck, Otsuka Pharmaceutical, Alter, Rovi, Casen Recordati, and Viatris.

All authors report no financial relationship relevant to the subject of this article.

Figures

Figure 1.
Figure 1.
General linear model mean predicted estimated value for Local Gyrification Index for the left cingulate area covariated by sex, age, chlorpromazine equivalent dose, diagnostic group (FEP patients/HCs), OCs (presence/absence), and the interaction between OCs and the diagnostic group. Note: FEP, first episode psychosis; HC, healthy controls; OCs, obstetric complications.
See this image and copyright information in PMC

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