Overview on cognitive impairment in psychotic disorders: From impaired microcircuits to dysconnectivity

Schizophrenia's cognitive deficits, often overshadowed by positive symptoms, significantly contribute to the disorder's morbidity. Increasing attention highlights these deficits as reflections of neural circuit dysfunction across various cortical regions. Numerous connectivity alterations linked to cognitive symptoms in psychotic disorders have been reported, both at the macroscopic and microscopic level, emphasizing the potential role of plasticity and microcircuits impairment during development and later stages. However, the heterogeneous clinical presentation of cognitive impairment and diverse connectivity findings pose challenges in summarizing them into a cohesive picture. This review aims to synthesize major cognitive alterations, recent insights into network structural and functional connectivity changes and proposed mechanisms and microcircuit alterations underpinning these symptoms, particularly focusing on neurodevelopmental impairment, E/I balance, and sleep disturbances. Finally, we will also comment on some of the most recent and promising therapeutic approaches that aim to target these mechanisms to address cognitive symptoms. Through this comprehensive exploration, we strive to provide an updated and nuanced overview of the multiscale connectivity impairment underlying cognitive impairment in psychotic disorders.