Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis

AbstractBackgroundPatients with 22q11.2 deletion syndrome (22q11DS) present a high risk of developing psychosis. While clinical and cognitive predictors for the conversion towards a full-blown psychotic disorder are well defined and largely used in practice, neural biomarkers do not yet exist. However, a number of investigations indicated an association between abnormalities in cortical morphology and higher symptoms severities in patients with 22q11DS. Nevertheless, few studies included homogeneous groups of patients differing in their psychotic symptoms profile.MethodsIn this study, we included 22 patients meeting the criteria for an ultra-high-risk (UHR) psychotic state and 22 age-, gender- and IQ-matched non-UHR patients. Measures of cortical morphology, including cortical thickness, volume, surface area and gyrification, were compared between the two groups using mass-univariate and multivariate comparisons. Furthermore, the development of these measures was tested in the two groups using a mixed-model approach.ResultsOur results showed differences in cortical volume and surface area in UHR patients compared with non-UHR. In particular, we found a positive association between surface area and the rate of change of global functioning, suggesting that higher surface area is predictive of improved functioning with age. We also observed accelerated cortical thinning during adolescence in UHR patients with 22q11DS.ConclusionsThese results, although preliminary, suggest that alterations in cortical volume and surface area as well as altered development of cortical thickness may be associated to a greater probability to develop psychosis in 22q11DS.

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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

PLoS ONE ◽

10.1371/journal.pone.0159928 ◽

2016 ◽

Vol 11 (11) ◽

pp. e0159928 ◽

Cited By ~ 13

Author(s):

Geor Bakker ◽

Matthan W. A. Caan ◽

Wilhelmina A. M. Vingerhoets ◽

Fabiana da Silva- Alves ◽

Mariken de Koning ◽

...

Keyword(s):

High Risk ◽

Psychotic Disorder ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Ultra High Risk ◽

Cortical Morphology

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Brain morphometry in 22q11.2 deletion syndrome: an exploration of differences in cortical thickness, surface area, and their contribution to cortical volume

Scientific Reports ◽

10.1038/s41598-020-75811-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

M. Gudbrandsen ◽

E. Daly ◽

C. M. Murphy ◽

C. E. Blackmore ◽

M. Rogdaki ◽

...

Keyword(s):

Surface Area ◽

Cortical Thickness ◽

Neuropsychiatric Symptoms ◽

22Q11.2 Deletion Syndrome ◽

Structural Mri ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Cortical Volume ◽

Brain Morphometry ◽

Relative Contribution

Abstract 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion in humans, with a heterogenous clinical presentation including medical, behavioural and psychiatric conditions. Previous neuroimaging studies examining the neuroanatomical underpinnings of 22q11.2DS show alterations in cortical volume (CV), cortical thickness (CT) and surface area (SA). The aim of this study was to identify (1) the spatially distributed networks of differences in CT and SA in 22q11.2DS compared to controls, (2) their unique and spatial overlap, as well as (3) their relative contribution to observed differences in CV. Structural MRI scans were obtained from 62 individuals with 22q11.2DS and 57 age-and-gender-matched controls (aged 6–31). Using FreeSurfer, we examined differences in vertex-wise estimates of CV, CT and SA at each vertex, and compared the frequencies of vertices with a unique or overlapping difference for each morphometric feature. Our findings indicate that CT and SA make both common and unique contributions to volumetric differences in 22q11.2DS, and in some areas, their strong opposite effects mask differences in CV. By identifying the neuroanatomic variability in 22q11.2DS, and the separate contributions of CT and SA, we can start exploring the shared and distinct mechanisms that mediate neuropsychiatric symptoms across disorders, e.g. 22q11.2DS-related ASD and/or psychosis/schizophrenia.

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P.3.b.026 Differences in cortical morphology between 22q11.2 deletion syndrome patients and patients at ultra-high risk for psychotic disorders

European Neuropsychopharmacology ◽

10.1016/s0924-977x(15)30650-7 ◽

2015 ◽

Vol 25 ◽

pp. S478

Author(s):

G. Bakker ◽

M.W.A. Caan ◽

W.A.M. Vingerhoets ◽

F. Da Silva-Alves ◽

M. De Koning ◽

...

Keyword(s):

High Risk ◽

Psychotic Disorders ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Ultra High Risk ◽

Cortical Morphology

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Dopamine in high-risk populations: A comparison of subjects with 22q11.2 deletion syndrome and subjects at ultra high-risk for psychosis

Psychiatry Research Neuroimaging ◽

10.1016/j.pscychresns.2017.11.014 ◽

2018 ◽

Vol 272 ◽

pp. 65-70 ◽

Cited By ~ 3

Author(s):

Claudia Vingerhoets ◽

Oswald J.N. Bloemen ◽

Erik Boot ◽

Geor Bakker ◽

Mariken B. de Koning ◽

...

Keyword(s):

High Risk ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Ultra High Risk ◽

High Risk Populations

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Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome

World Psychiatry ◽

10.1002/wps.20347 ◽

2016 ◽

Vol 15 (3) ◽

pp. 259-265 ◽

Cited By ~ 32

Author(s):

Maude Schneider ◽

Marco Armando ◽

Maria Pontillo ◽

Stefano Vicari ◽

Martin Debbané ◽

...

Keyword(s):

High Risk ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Risk Status ◽

Ultra High Risk

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Ultra High Risk Status and Transition to Psychosis in 22q11.2 Deletion Syndrome

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.258 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S81-S82

Author(s):

M. Armando ◽

M. Schneider ◽

M. Pontillo ◽

S. Vicari ◽

M. Debbane ◽

...

Keyword(s):

High Risk ◽

Predictive Value ◽

Transition Rate ◽

22Q11.2 Deletion Syndrome ◽

Human Model ◽

Deletion Syndrome ◽

Additional Contribution ◽

22Q11.2 Deletion ◽

Level Of Functioning ◽

Ultra High Risk

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high-risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of sociodemographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.56176 months after initial assessment. Eighty-nine participants with 22q11DS (age range: 8–30 years; mean: 16.1647) were assessed using the structured interview for psychosis-risk syndromes. Information on axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non-UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high-risk samples. Nevertheless, the relatively high transition rate in non-UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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ADOLESCENTS WITH 22q11.2 DELETION SYNDROME: A POPULATION ULTRA HIGH-RISK FOR SCHIZOPHRENIA

Schizophrenia Research ◽

10.1016/s0920-9964(08)70057-4 ◽

2008 ◽

Vol 102 (1-3) ◽

pp. 17

Author(s):

Martin Debbane ◽

Martial Van der Linden ◽

Marie Schaer ◽

Bronwyn Glaser ◽

Stephan Eliez

Keyword(s):

High Risk ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Ultra High Risk

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Associations between neurodevelopmental genes, neuroanatomy, and ultra high risk symptoms of psychosis in 22q11.2 deletion syndrome

American Journal of Medical Genetics Part B Neuropsychiatric Genetics ◽

10.1002/ajmg.b.32515 ◽

2017 ◽

Vol 174 (3) ◽

pp. 295-314 ◽

Cited By ~ 10

Author(s):

Carlie A. Thompson ◽

Jason Karelis ◽

Frank A. Middleton ◽

Karen Gentile ◽

Ioana L. Coman ◽

...

Keyword(s):

High Risk ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

22Q11.2 Deletion ◽

Ultra High Risk

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Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms

10.1101/2020.11.03.20221978 ◽

2020 ◽

Author(s):

Joëlle Bagautdinova ◽

Daniela Zöller ◽

Marie Schaer ◽

Maria Carmela Padula ◽

Valentina Mancini ◽

...

Keyword(s):

Cortical Thickness ◽

Mixed Model ◽

Superior Temporal Gyrus ◽

22Q11.2 Deletion Syndrome ◽

Structural Mri ◽

Brain Maturation ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

22Q11.2 Deletion ◽

Cortical Thinning

AbstractSchizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1-6 time points were collected from 324 participants aged 5-35 years (N=148 22q11DS, N=176 controls), resulting in a total of 636 scans (N=334 22q11DS, N=302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N=61, 146 scans), or remained exempt of (N=47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in fronto-temporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly fronto-temporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.

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