Neurocognitive Deficits Mediate the Relationship Between Structural Abnormalities and Clinical Outcomes in Individuals With Ultrahigh Risk for Psychosis: A Multimodal Neuroimaging and Longitudinal Neurocognitive Study

Cognitive deficits and improvements have been observed in individuals with ultrahigh risk for psychosis (UHR) over their clinical course, but the relationship between brain structural and functional characteristics, neurocognitive deficits and improvements, and clinical prognosis remains unclear. A total of 50 UHR individuals were assessed using 129 neurocognitive assessments to explore cognitive deficits and improvements over 3 years. Neurocognitive deficits (intercept) and improvements (slope) were investigated using a general linear mixed model, and their relationship with symptom severity was assessed using the Positive and Negative Syndrome Scale five factor scores. In addition, psychobiological measurements including brain structure, brain activity during a verbal fluency task, and mismatch negativity were also tested. Possible models including the paths from brain structure, brain function, neurocognitive function, and symptom severity outcomes were compared. The intercept of verbal fluency was negatively associated with negative symptoms at baseline (corrected P = .0001) and at the 4-month follow-up (corrected P = .0016).A model including these relationships exhibited significant paths from the cortical surface area in the right banks of the superior temporal sulcus to verbal fluency (P < .001) and from verbal fluency to 4-month negative symptoms (P < .001), but not from brain activity to negative symptoms (P = .072). Structural and functional characteristics of the brain may not be directly associated with short-term symptom severity, and these relationships may be partly mediated by neurocognitive function.