Cortical Morphology Differences in Subjects at Increased Vulnerability for Developing a Psychotic Disorder: A Comparison between Subjects with Ultra-High Risk and 22q11.2 Deletion Syndrome.
BACKGROUND
Subjects with 22q11.2 deletion syndrome (22q11DS) and subjects with ultra-high risk for psychosis (UHR) share a risk of approximately 30% to develop a psychotic disorder. Studying these groups helps identify biological markers of pathophysiological processes involved in the development of psychosis. Total cortical surface area (cSA), total cortical grey matter volume (cGMV), cortical thickness (CT), and local gyrification index (LGI) of the cortical structure have a distinct neurodevelopmental origin making them important target markers to study in relation to the development of psychosis.


METHODS
Structural T1-weighted high resolution images were acquired using a 3 Tesla Intera MRI system in 18 UHR subjects, 18 22q11DS subjects, and 24 matched healthy control (HC) subjects. Total cSA, total cGMV, mean CT, and regional vertex-wise differences in CT and LGI were assessed using FreeSurfer software. The Positive and Negative Syndrome Scale was used to assess psychotic symptom severity in UHR and 22q11DS subjects at time of scanning.


RESULTS
22q11DS subjects had lower total cSA and total cGMV compared to UHR and HC subjects. The 22q11DS subjects showed bilateral lower LGI in the i) prefrontal cortex, ii) precuneus, iii) precentral gyrus and iv) cuneus compared to UHR subjects. Additionally, lower LGI was found in the left i) fusiform gyrus and right i) pars opercularis, ii) superior, and iii) inferior temporal gyrus in 22q11DS subjects compared to HC. In comparison to 22q11DS subjects, the UHR subjects had lower CT of the insula. For both risk groups, positive symptom severity was negatively correlated to rostral middle frontal gyrus CT.


CONCLUSIONS
A shared negative correlation between positive symptom severity and rostral middle frontal gyrus CT in UHR and 22q11DS may be related to their increased vulnerability to develop a psychotic disorder. 22q11DS subjects were characterised by widespread lower degree of cortical gyrification linked to early and postnatal neurodevelopmental pathology. No implications for early neurodevelopmental pathology were found for the UHR subjects, although they did have distinctively lower insula CT which may have arisen from defective pruning processes during adolescence. Implications of these findings in relation to development of psychotic disorders are in need of further investigation in longitudinal studies.
Department of Psychiatry & Psychology, University of Maastricht, Maastricht, The Netherlands.|Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Geor
G
Bakker
Department of Radiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Matthan W A
MW
Caan
Department of Psychiatry & Psychology, University of Maastricht, Maastricht, The Netherlands.|Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Wilhelmina A M
WA
Vingerhoets
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Fabiana
F
da Silva-Alves
Arkin Mental Health Care, Amsterdam, The Netherlands.
Mariken
M
de Koning
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|The Dalglish Family 22q Clinic, Toronto, Ontario, Canada.
Erik
E
Boot
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Dorien H
DH
Nieman
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Arkin Mental Health Care, Amsterdam, The Netherlands.
Lieuwe
L
de Haan
Department of Psychiatry & Psychology, University of Maastricht, Maastricht, The Netherlands.|GGZ Centraal, Center for Mental Health Care Innova, Amersfoort, The Netherlands.
Oswald J
OJ
Bloemen
Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Jan
J
Booij
Department of Psychiatry & Psychology, University of Maastricht, Maastricht, The Netherlands.|Department of Nuclear Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Thérèse A M J
TA
van Amelsvoort
D000328:Adult; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000473:pathology*; D004062:DiGeorge Syndrome / Q000000981:diagnostic imaging / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000473:pathology*; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D011618:Psychotic Disorders / Q000000981:diagnostic imaging / Q000473:pathology*; D018570:Risk Assessment; D012307:Risk Factors; D014057:Tomography, X-Ray Computed; D055815:Young Adult