Is it possible to identify early signs of schizophrenia in the brains of children?

Schizophrenia is a complex disorder that typically manifests in late adolescence or early adulthood. However, scientists have long suspected that its origins begin much earlier. The key question is whether it is possible to detect risk markers during childhood, before the onset of clear clinical symptoms. A recent study sought to address this question by examining brain development in children at increased risk of developing the disorder.

The study, based on the longitudinal Child Health and Development Study (CHADS) project and coordinated by Kristin Robyn Laurens, was conducted by an international research team and included 88 children aged between 9 and 12 years at baseline. Participants were divided into three groups: one with multiple developmental antecedents associated with an increased risk of schizophrenia, another with a family history of the disorder, and a comparison group of typically developing children. Over approximately four years, researchers used structural magnetic resonance imaging (MRI) to track changes in the volume of different brain structures.

The findings revealed a consistent pattern: children at higher risk exhibited greater white matter volume (the tissue responsible for communication between different brain regions) compared to children without identified risk. This pattern remained stable across multiple assessments, suggesting that these differences may emerge early in brain development.

In contrast, no stable differences were observed between groups in grey matter volume (which is generally associated with information processing). Nevertheless, in children with a family history of schizophrenia, some longitudinal changes were observed in specific brain regions involved in memory, emotion, and perception. However, these effects did not remain statistically significant after correction for multiple comparisons and therefore should be interpreted with caution.

Overall, these findings suggest that the brains of children at risk for schizophrenia may exhibit subtle structural differences even before the emergence of clinical symptoms. Although it is not yet possible to predict which individuals will go on to develop the disorder, this line of research highlights the importance of early detection and longitudinal monitoring during development. In the long term, a better understanding of these developmental trajectories may help identify early warning signs and support the development of more timely and effective intervention strategies.

The study was published in the journal CNS Spectrums under the title “Trajectories of grey and white matter volume in children at elevated risk for schizophrenia”, as part of project 194/12 - Characterising developmental trajectories of brain function from childhood into adolescence, supported by the Fundação Bial.

ABSTRACT

Objective: Longitudinal investigation of brain alterations in children putatively at-risk of developing schizophrenia may identify early markers of pathophysiology associated with vulnerability for the disorder. Methods: Children aged 9-12 years with multiple antecedents of schizophrenia (psychoticlike experiences; speech and/or motor delays; and social, emotional, and/or behavioural difficulties; ASz, n=31), with a family history of schizophrenia/schizoaffective disorder (FHx, n=21), and typically developing children (TD, n=35) were recruited through community screening using questionnaires. T1-weighted structural MRI scans were obtained at baseline, and after approximately 2- and 4-years of follow-up, and processed using the FreeSurfer longitudinal pipeline. Across these three assessment waves, total grey matter (GM) and white matter (WM) volume, and regional GM volumes in twelve regions of interest, were compared among the groups using linear mixed models. Results: Children from three groups were 11.21 (±1.61) years at baseline and the average lapse-of-time between each assessment was 1.76 (±0.36) years. The ASz group exhibited consistently higher total WM volume (b=29.45) compared to the TD group, with no statistically significant time-related volumetric WM or GM differences in any region. The FHx group also demonstrated higher total WM volume (b=36.49), and time-related total and regional GM volume changes were observed; however, these effects were attenuated after correction. Conclusion: Global and regionally-specific brain abnormalities distinguished children with different risk profiles for schizophrenia relative to their typically developing peers. Follow-up is required to determine how these changes may relate to later schizophrenia.