“The glue that holds the pieces together”: Unlocking Cognitive Health in Psychotic Disorders

Psychotic disorders like schizophrenia have a strong neurodevelopmental component, yet symptoms often do not emerge until adolescence or early adulthood. Cognitive impairments are among the earliest and most disabling symptoms. Intriguingly, our research reveals that many brain alterations linked to these impairments resemble those associated with premature ageing, such as brain atrophy and advanced brain age. Understanding the neurodevelopmental pathways of these cognitive impairments is crucial for creating effective early interventions. We aim to combat cognitive impairment in psychotic disorders as early as possible by: 1) Understanding the developmental features of brain age acceleration in psychotic disorders and what risk factors might exacerbate these, using large-scale neuroimaging datasets and computationally advanced methods; 2) Characterising the cellular changes associated with advanced brain age, using experimental mouse models for schizophrenia; 3) Identifying proteomic treatment targets that could prevent or slow down cognitive impairment in psychotic disorders, using prospective proteomic samples (of individuals who later went on to develop psychosis). Our goal is to unravel advanced brain age at a cellular level, embed this within a neurodevelopmental framework, and identify effective treatment targets for early intervention against cognitive impairments in psychotic disorders to mitigate cognitive impairments at the earliest stages of the disease.