Cortical folding defects as markers of poor treatment response in first episode psychosis

Context: At present, no reliable predictors exist to distinguish future responders from non-responders to treatment during the first episode of psychosis (FEP). Among potential neuroimaging predictors of treatment response, gyrification represents an important marker of the integrity of normal cortical development that may characterise, already at illness onset, a subgroup of patients with particularly poor outcome.

Objective: We test the hypothesis that patients with FEP who do not respond to 12 weeks of antipsychotic treatment have, already at illness onset, significant gyrification defects.

Design: Case-control structural magnetic resonance imaging study with 12-weeks longitudinal follow-up to determine treatment response.

Participants: 126 subjects, including 80 patients presenting with FEP and 46 healthy controls. Patients were scanned at the outset and received various antipsychotic medications in a naturalistic clinical setting. They were followed up for 12-weeks and classified as Responders or Non-Responders if they reached criteria for symptom remission, evaluated with the Psychiatric and Personal History Schedule (PPHS).

Setting: Secondary psychiatric services in an inner city area (South London, United Kingdom).

Outcome: Cortical gyrification was assessed using local gyrification index (LGI) in a vertex-wise fashion across the entire cortical surface with correction for multiple testing using permutation analysis. Differences in LGI were assessed between Responders, Non-Responders, and healthy controls. The effect of diagnosis (affective vs. non-affective psychosis) on the LGI was also investigated in Responders and Non-Responders.

Results: Patients with FEP showed a significant reduction in gyrification (hypogyria) across multiple brain regions, compared to healthy controls. Interestingly, Non-Responders showed prominent hypogyria at bilateral insular, left frontal and right temporal regions when compared to Responders (all clusters significant at p<0.05). These effects were present for both affective and non-affective psychoses.

Conclusions: Gyrification appears to be a useful predictor of antipsychotic treatment response. Early neurodevelopmental aberrations may predict unfavourable prognosis in psychosis, irrespective of the existing diagnostic boundaries.