Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study

Aberrant cortical gyrification in schizophrenia: a surface-based morphometry study

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J Psychiatry Neurosci 2012;37(6):399-406

Lena Palaniyappan, MBBS; Peter F. Liddle, BMBCh, PhD

Palaniyappan, Liddle — Division of Psychiatry, University of Nottingham, South Block, Queen’s Medical Centre, Nottingham, United Kingdom


Background: Schizophrenia is considered to be a disorder of cerebral connectivity associated with disturbances of cortical development. Disturbances in connectivity at an early period of cortical maturation can result in widespread defects in gyrification. Investigating the anatomic distribution of gyrification defects can provide important information about neurodevelopment in patients with schizophrenia.

Methods: We undertook an automated surface-based morphometric assessment of gyrification on 3-dimensionally reconstructed cortical surfaces across multiple vertices that cover the entire cortex. We used a sample from our previous research of 57 patients (50 men) with schizophrenia and 41 controls (39 men) in whom we had tested a specific hypothesis regarding presence of both hypoand hypergyria in the prefrontal cortex using a frontal region-of-interest approach.

Results: Regions with significant reductions in gyrification (hypogyria) were seen predominantly in the left hemisphere, involving the insula and several regions of the multimodal association cortex. Although the prefrontal hypergyria documented earlier did not survive the statistical correction required for a whole brain search (cluster inclusion at p = 0.0001), significant hypergyric frontal clusters emerged when the threshold was lowered (cluster inclusion at p = 0.05). In the insula, a reduction in gyrification was related to reduced cortical thickness in patients with schizophrenia.

Limitations: We studied a sample of patients taking antipsychotic medications, which could have confounded the results. Our sample was predominantly male, limiting the generalizability of our findings.

Conclusion: Our observations suggest that the disturbances in cortical gyrification seen in patients with schizophrenia might be related to a disrupted interaction between the paralimbic and the multimodal association cortex and thus might contribute to the pathogenesis of the illness.

Submitted Aug. 31, 2011; Revised Dec. 30, 2011, Feb. 22, 2012; Accepted Feb. 24, 2012.

Acknowledgements: This work was supported by a New Investigator grant from the University of Nottingham and an Interdisciplinary Research Award from the Nottingham Institute of Neuroscience, University of Nottingham. We are grateful to the volunteers who participated in this study and would like to acknowledge Pavan Mallikarjun and Verghese Joseph for clinical recruitment. We would like to thank Thomas White, Kathrin Doege, Dawn-Marie Walker and Dorothee Auer for assisting the data acquisition.

Competing interests: L. Palaniyappan has received a Young Investigator Travel Fellowship from Eli Lilly. P.F. Liddle has received honor aria for academic presentations from GlaxoSmithKline, AstraZeneca, Janssen-Cilag, Bristol Myers Squibb and Eli Lilly; has taken part in advisory panels for Bristol Myers Squibb, Eli Lilly, Pfizer and GlaxoSmithKline; has received institutional grant support from the Medical Research Council (G0601442 and MR/J01186X/1) and the Dr. Hadwen Trust; and receives book royalties from the Royal College of Psychiatrists.

Contributors: Both authors contributed to study design, data acquisition and analysis, article writing and review and approved article publication.

DOI: 10.1503/jpn.110119

Correspondence to: L. Palaniyappan, Division of Psychiatry, A Floor, South Block, Queen’s Medical Centre, Nottingham, NG7 2UH, England, United Kingdom; Lena.Palaniyappan@nottingham.ac.uk