Braam, E.E. (Esmée) (2017) Structural Brain Correlates of Neurological Soft Signs in Antipsychotic Naïve Individuals at Ultra High-Risk for Psychosis. thesis, Medicine.
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Abstract
Background: Neurological soft signs (NSS) occur more frequently across different stages of patients who suffer from schizophrenia and psychosis, as well as in unaffected relatives and individuals at ultra high-risk (UHR) for developing psychosis, than in the general population. This has led many researchers to conceptualize NSS as a vulnerability marker for the illness. A number of studies using structural Magnetic Resonance Imaging (MRI) techniques have examined the links between increased NSS scores and brain morphology in individuals with established schizophrenia and first-episode psychosis. These studies have found that increased severity of NSS is associated with brain abnormalities in a number of regions such as the preand post-central gyri, the lingual gyri, the caudate nucleus, the putamen, the thalamus, the globus pallidus and the cerebellum, suggesting that deficits in cerebello-thalamo-cortico structures might underlie NSS. Although an increased prevalence of NSS has been observed in UHR individuals, the correlation between NSS and gray matter volume (GMV) in UHR individuals has not been examined in this high risk group. Aim: To investigate whether severity of NSS is associated with smaller GMV in cortical, subcortical and cerebellar structures in individuals at UHR for developing psychosis, and to determine whether this relationship is specific to individuals who did develop a psychotic disorder (UHR-P) relative to individuals who did not develop psychosis (UHR-NP) and healthy controls (HC). Method: Structural T1-weighted MRI scans of brain anatomy were obtained from 56 antipsychotic naïve individuals identified as being at UHR for developing psychosis and 35 HC. NSS were assessed by the Neurological Evaluation Scale (NES). MR images were preprocessed using unified voxel-based morphometry (VBM). 47 UHR individuals were followed between 2 and 12 years (mean: 7.5) to determine who transitioned to psychosis and who did not. Cluster-based statistics were employed to identify brain regions where GMV was associated with NSS total and subscale scores. Statistical analyses were corrected for age, sex and total intracranial volume (TIV). Regions of interest (ROIs) analyses were also performed. Results: NSS total and subscale scores were significantly higher in UHR individuals compared to HC. NSS scores did not differ significantly between UHR-P (n = 23) and UHR-NP individuals (n = 24). There were no significant interactions correlating NSS scores with GMV in UHR individuals compared to HC. A negative significant correlation between higher scores of the ‘other’ subscale and lower GMV in parts of the left cingulate gyrus was found in HC. Also, there was a significant negative correlation between higher NSS total scores and lower GMV in parts of the cerebellum in UHR individuals, irrespective of subsequent transition. Similar correlations were found for the ‘sensory integration’ and ‘sequencing of complex motor acts’ subscales in this sample. UHR-P did not show significant correlations between NSS scores and GMV. UHR-NP individuals showed the same negative correlation between higher NSS total scores and lower GMV in the cerebellar cluster. No significant interactions were found between the transition groups. Discussion: NSS might be used to differentiate UHR individuals from the general population, but may not be a specific predictor for the development of psychosis in UHR individuals. Our findings suggest that NSS, particularly those involving sensory function (including audio-visual integration, stereognosis, graphesthesia, extinction and right/left confusion), might be an expression of specific deficits of GMV in parts of the cerebellum. The lack of an association between NSS and brain morphology in UHR-P individuals suggests that the brain abnormalities underlying these signs are not specific to a psychotic disorder but, rather, might be a nonspecific marker of a neurodevelopmental insult. These findings suggest that lower GMV in parts of the cerebellum underlie neurological soft signs in UHR individuals and support the neurodevelopmental model of schizophrenia.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Scientific supervisor UMCG: and Tol, Dr. M.J. van and GIPS-M supervisor: and Kallenberg, Prof. dr. C.G.M. |
| Supervisor name: | Scientific supervisor MNC: and Cropley, Dr. V.L. and Co-supervisors MNC: and Pantelis, Prof. dr. C. and Zalesky, Dr. A. and University of Melbourne and Melbourne Neuropsychiatric Centre |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:45 |
| Last Modified: | 25 Jun 2020 10:45 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/682 |
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