Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome

Approximately 30% of individuals with 22q11.2 Deletion Syndrome (22q11DS) develop schizophrenia during adolescence/early adulthood, making this syndrome a model for the disorder. Furthermore, negative symptoms exist in up to 80% of patients diagnosed with 22q11DS. The present study aims to uncover morphological brain alterations associated with negative symptoms in a cohort of patients with 22q11DS who are at-risk for developing schizophrenia. A total of 71 patients with 22q11DS aged 12 to 35 (54% females) with no past or present diagnosis of a schizophrenia were included in the study. Psychotic symptom scores were used to divide patients into subgroups by means of a cluster analysis. Three major subgroups were evident: patients with low negative and positive symptoms; patients with high negative symptoms and low positive symptoms; and patients with high negative and positive symptoms. Cortical volume, thickness and gyrification were compared between subgroups using FreeSurfer software. Results showed that patients with high negative symptoms, compared to those with low negative symptoms, have decreased gyrification in the medial occipito-temporal (MOT) and lateral temporo-parietal (LTP) cortices of the left hemisphere, and in the medial temporal (MT)/posterior cingulate (PCC) cortices of the right hemisphere. These findings suggest that high negative symptoms are associated with gyrification reductions predominantly in medial occipital and temporal regions, which are areas implicated in social cognition and early visual processing. Furthermore, as cortical folding develops in utero and during the first years of life, reduced gyrification may represent an early biomarker predicting the development of negative symptoms.