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Cortical-amygdala volumetric ratios predict onset of symptoms of psychosis in 22q11.2 deletion syndrome.

ABSTRACT: Dysfunction of cortical circuitry involving prefrontal cortex, cingulate gyrus and mesial temporal lobe has been implicated in the pathophysiology of psychotic symptoms. 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that comports a 25-fold increased risk of developing psychosis. Morphological changes in the neuroanatomy of this syndrome may represent a biological risk factor for the development of psychosis. The present study explored ratios between cortical volumes and the amygdala. We also explored relationships between these ratios and the eventual development of psychosis in youth with 22q11DS. A group of 73 individuals with 22q11DS, 32 community controls, and 27 unaffected siblings were followed every three years, at four timepoints. We analyzed baseline ratios between 34 bilateral FreeSurfer-generated cortical volumes and amygdala, and examined whether baseline cortical ratios predicted positive symptoms of psychosis 12 years later, at the 4th timepoint. Youth with 22q11DS demonstrated significantly smaller cortical volume-to-amygdala ratios in left anterior cingulate, occipital and parietal cortices. An increased risk of developing psychotic episodes in individuals with 22q11DS was associated with a lower cortical volume- to-amygdala ratio, suggesting that cortico-limbic circuitry may play an important role in emotional modulation and may underlie the pathophysiology of positive symptoms of psychosis.

SUBMITTER: Berhanu D

PROVIDER: S-EPMC5456453 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Cortical-amygdala volumetric ratios predict onset of symptoms of psychosis in 22q11.2 deletion syndrome.

Berhanu David D Mattiaccio Leah M LM Antshel Kevin M KM Fremont Wanda W Middleton Frank A FA Kates Wendy R WR

Psychiatry research. Neuroimaging 20161125

Dysfunction of cortical circuitry involving prefrontal cortex, cingulate gyrus and mesial temporal lobe has been implicated in the pathophysiology of psychotic symptoms. 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that comports a 25-fold increased risk of developing psychosis. Morphological changes in the neuroanatomy of this syndrome may represent a biological risk factor for the development of psychosis. The present study explored ratios between cortical volumes and the amyg ...[more]

PMID: 27918911

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Project description:Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.To determine whether early cognitive decline is associated with risk of psychotic disorder in 22q11DS.Prospective longitudinal cohort study. As part of an international research consortium initiative, we used the largest data set of intelligence (IQ) measurements in patients with 22q11DS reported to date to investigate longitudinal IQ trajectories and the risk of subsequent psychotic illness. A total of 829 patients with a confirmed hemizygous 22q11.2 deletion, recruited through 12 international clinical research sites, were included. Both psychiatric assessments and longitudinal IQ measurements were available for a subset of 411 patients (388 with ?1 assessment at age 8-24 years).Diagnosis of a psychotic disorder, initial IQ, longitudinal IQ trajectory, and timing of the last psychiatric assessment with respect to the last IQ test.Among 411 patients with 22q11DS, 55 (13.4%) were diagnosed as having a psychotic disorder. The mean (SD) age at the most recent psychiatric assessment was 16.1 (6.2) years. The mean (SD) full-scale IQ at first cognitive assessment was lower in patients who developed a psychotic disorder (65.5 [12.0]) compared with those without a psychotic disorder (74.0 [14.0]). On average, children with 22q11DS showed a mild decline in IQ (full-scale IQ, 7.04 points) with increasing age, particularly in the domain of verbal IQ (9.02 points). In those who developed psychotic illness, this decline was significantly steeper (P?<?.001). Those with a negative deviation from the average cognitive trajectory observed in 22q11DS were at significantly increased risk for the development of a psychotic disorder (odds ratio?=?2.49; 95% CI, 1.24-5.00; P?=?.01). The divergence of verbal IQ trajectories between those who subsequently developed a psychotic disorder and those who did not was distinguishable from age 11 years onward.In 22q11DS, early cognitive decline is a robust indicator of the risk of developing a psychotic illness. These findings mirror those observed in idiopathic schizophrenia. The results provide further support for investigations of 22q11DS as a genetic model for elucidating neurobiological mechanisms underlying the development of psychosis.

Project description:The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.

Dataset Information

Cortical-amygdala volumetric ratios predict onset of symptoms of psychosis in 22q11.2 deletion syndrome.

Publications

Cortical-amygdala volumetric ratios predict onset of symptoms of psychosis in 22q11.2 deletion syndrome.

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