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Changes in occipital lobe gyrification may be an early marker for psychosis in youth with velo-cardio-facial syndrome
  1. Jean Starling
  1. Walker Unit, Concord Centre for Mental Health, Concord, West, New South Wales, Australia

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Question

Question: Is cortical gyrification a marker for psychosis in children and adolescents with velo-cardio-facial syndrome (VCFS)?

Population: 58 children aged 9–15 years with VCFS plus 21 unaffected siblings and 18 community controls in the same age range were assessed in the longitudinal part of the study. In addition, 91 children aged 6–9 years with VCFS, 29 unaffected siblings and 54 community controls were assessed cross-sectionally and their data pooled with the longitudinal sample's baseline assessment.

Setting: USA; time period not stated.

Prognostic factors: Cortical gyrification, quantified as the gyrification index (GI) using MRI.

Outcomes: Prodromal symptoms of psychosis (Scale of Prodromal Symptoms, SOPS). The SOPS categorises symptoms into: positive, negative, disorganised and general symptoms.

Methods

Design: Prospective cohort study.

Follow-up period: Three years (range 1.5–5.3 years).

Main results

At baseline, there was a significant difference in age between those with VCFS, their siblings and the community controls (p=0.01; due to the inclusion of the two different age groups at this time point), but not at 3 year follow-up (when only the older age group was analysed). After controlling for age and gender, individuals with VCFS had significantly lower GIs in their frontal and parietal regions compared to their siblings and controls at both time points. Changes in GI did not differ between groups over time. All three groups showed a significant decrease in GI in the frontal, parietal and temporal regions at 3-year follow-up. Change in GI score over 3 years in the VCFS group was negatively correlated with positive prodromal symptoms of psychosis. After correction for multiple comparisons, this relationship remained significant for the left occipital region only (p=0.002). There was also a significant negative correlation between right occipital GI and total symptoms after correction (p=0.006).

Conclusions

Youth with VCFS have reduced cortical folds compared to sibling and community controls. There is no difference in the rate of change of GI among youth with VCFS compared to controls over 3 years. Changes in cortical gyrification in the occipital lobe over time are associated with prodromal symptoms of psychosis in youth with VCFS.

Notes

Loss to follow-up was 16% among children with VCFS, 21% among their siblings and 37% among the community controls. Individual with attention deficit hyperactivity disorder or learning disabilities were not excluded from the control groups.

Abstracted from

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Acknowledgments

Sources of funding The National Institutes of Health and National Alliance for Research in Schizophrenia and Depression (NARSAD)—now the Brain and Behavior Research Foundation.

Commentary

Velo-cardio-facial syndrome (VCFS) is the most common of the microdeletion syndromes and is associated with a wide range of physical, developmental and psychological abnormalities. Some studies report that almost a third of individuals with VCFS develop a psychotic disorder as an adult, suggesting that genes in the 22q11, the typically deleted area, are involved in the aetiology of schizophrenia, making VCFS a topic of great interest to schizophrenia researchers.

While there have been many studies describing structural MRI in VCFS subjects,1 to the author's knowledge this is the first study demonstrating an association between prodromal symptoms, measured using the Scale of Prodromal Symptoms Scale (SOPS) and reduced cortical folding seen on MRIs of children with VCFS. This group of authors have previously published studies about the reduction in brain volume and higher SOPS scores.2 The sample is large (91 subjects at baseline and 58 at follow-up) and has both sibling and normal controls. However, as the subjects were still adolescents, revisiting them in adult life to see if the earlier findings predicted the development of schizophrenia would confirm the significance of these findings.

Clinically, this article provides a preliminary biological rationale for screening teenagers with VCFS for psychotic symptoms. This would enable the early identification and treatment of psychotic symptoms which has been shown to improve outcomes in early psychosis cohorts in the community.3 However, the hypothesis that cortical gyrification could be a vulnerability marker for schizophrenia will require replication.

References

Footnotes

  • Competing interests None.