Carina Heller1, Saskia Steinmann2, James J Levitt3, Nikos Makris4, Kevin M Antshel5, Wanda Fremont6, Ioana L Coman7, Stefan R Schweinberger8, Thomas Weiß9, Sylvain Bouix10, Marek R Kubicki11, Wendy R Kates6, Zora Kikinis10. 1. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry and Psychotherapy, Jena University Hospital, Germany; Department of Clinical Psychology, Friedrich-Schiller-University Jena, Germany. Electronic address: carina.heller@uni-jena.de. 2. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Psychiatry Neuroimaging Branch, Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Brockton Division, Brockton, MA, USA. 4. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Departments of Psychiatry and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. 5. Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA; Department of Psychology, Syracuse University, Syracuse, NY, USA. 6. Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA. 7. Department of Computer Science, SUNY Oswego, Oswego, NY, USA. 8. Department of General Psychology, Friedrich-Schiller-University Jena, Germany. 9. Department of Clinical Psychology, Friedrich-Schiller-University Jena, Germany. 10. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 11. Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Abstract
BACKGROUND: Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating 22q11.2 deletion syndrome (22q11DS), a genetic syndrome associated with a 30% risk for developing schizophrenia in adulthood and a decline in Verbal IQ (VIQ) preceding psychosis onset. Here, we examined white matter (WM) tracts in FST sub-circuits, especially those in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC) sub-circuits, and their associations with VIQ in young adults with 22q11DS. METHODS: Diffusion MRI scans were acquired from 21 individuals with 22q11DS with prodromal symptoms of schizophrenia, 30 individuals with 22q11DS without prodromal symptoms, and 30 healthy controls (mean age: 21 ± 2 years). WM tracts were reconstructed between striatum and thalamus with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. Fractional anisotropy (FA) and radial diffusivity (RD) were used for group comparisons. VIQ was assessed and associations with the diffusion measures were evaluated. RESULTS: FA was significantly increased and RD decreased in most tracts of the DLPFC and VLPFC sub-circuits in 22q11DS. Verbal IQ scores correlated negatively with FA and, at trend level, positively with RD in the right thalamus-IFG tract in 22q11DS with prodromal symptoms. CONCLUSIONS: While abnormalities in FST sub-circuits are associated with schizophrenia, we observed that these abnormalities are also present in 22q11DS individuals with prodromal symptoms and are associated with verbal performance in the right thalamus-IFG tract.
BACKGROUND: Abnormalities in fronto-striatal-thalamic (FST) sub-circuits are present in schizophrenia and are associated with cognitive impairments. However, it remains unknown whether abnormalities in FST sub-circuits are present before psychosis onset. This may be elucidated by investigating 22q11.2 deletion syndrome (22q11DS), a genetic syndrome associated with a 30% risk for developing schizophrenia in adulthood and a decline in Verbal IQ (VIQ) preceding psychosis onset. Here, we examined white matter (WM) tracts in FST sub-circuits, especially those in the dorsolateral (DLPFC) and ventrolateral prefrontal cortex (VLPFC) sub-circuits, and their associations with VIQ in young adults with 22q11DS. METHODS: Diffusion MRI scans were acquired from 21 individuals with 22q11DS with prodromal symptoms of schizophrenia, 30 individuals with 22q11DS without prodromal symptoms, and 30 healthy controls (mean age: 21 ± 2 years). WM tracts were reconstructed between striatum and thalamus with rostral middle frontal gyrus (rMFG) and inferior frontal gyrus (IFG), representing DLPFC and VLPFC respectively. Fractional anisotropy (FA) and radial diffusivity (RD) were used for group comparisons. VIQ was assessed and associations with the diffusion measures were evaluated. RESULTS: FA was significantly increased and RD decreased in most tracts of the DLPFC and VLPFC sub-circuits in 22q11DS. Verbal IQ scores correlated negatively with FA and, at trend level, positively with RD in the right thalamus-IFG tract in 22q11DS with prodromal symptoms. CONCLUSIONS: While abnormalities in FST sub-circuits are associated with schizophrenia, we observed that these abnormalities are also present in 22q11DS individuals with prodromal symptoms and are associated with verbal performance in the right thalamus-IFG tract.
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