Association between Psychotic Symptoms and Cortical Thickness Reduction across the Schizophrenia Spectrum

Laboratory of Neuroscience, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Johann Wolfgang Goethe-University, 60528 Frankfurt/Main, Germany.
Cerebral Cortex (Impact Factor: 8.67). 01/2012; 23(1). DOI: 10.1093/cercor/bhr380
Source: PubMed


The current study provides a complete magnetic resonance imaging (MRI) analysis of thickness throughout the cerebral cortical mantle in patients with schizophrenia (SZ) and rigorously screened and matched unaffected relatives and controls and an assessment of its relation to psychopathology and subjective cognitive function. We analyzed 3D-anatomical MRI data sets, obtained at 3 T, from 3 different subject groups: 25 SZ patients, 29 first-degree relatives, and 37 healthy control subjects. We computed whole-brain cortical thickness using the Freesurfer software and assessed group differences. We also acquired clinical and psychometric data. The results showed markedly reduced cortical thickness in SZ patients compared with controls, most notably in the frontal and temporal lobes, in the superior parietal lobe and several limbic areas, with intermediate levels of cortical thickness in relatives. In both patients and relatives, we found an association between subjective cognitive dysfunction and reduced thickness of frontal cortex, and predisposition toward hallucinations and reduced thickness of the superior temporal gyrus. Our findings suggest that changes in specific cortical areas may predispose to specific symptoms, as exemplified by the association between temporal cortex thinning and hallucinations.

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    • "A limitation of this study includes our modest sample size. However, our sample size was similar to most other structural MRI studies of schizophrenia patients and relatives [Marcelis et al., 2003; Oertel-Knochel et al., 2013] "
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    ABSTRACT: Schizophrenia is associated with abnormalities in cortical thickness, including both thicker and thinner cortices than controls. Although less reliably than in patients, non-psychotic relatives of schizophrenia patients have also demonstrated both thicker and thinner cortices than controls, suggesting an effect of familial or genetic liability. We investigated cortical thickness in 25 schizophrenia patients, 26 adult non-psychotic first-degree biological relatives, and 23 community controls using the automated program FreeSurfer. Contrary to hypotheses, we found relatives of schizophrenia patients had greater cortical thickness in all lobes compared to patients and controls; however, this finding was not as widespread when compared to controls. In contrast, schizophrenia patients only demonstrated a thinner right fusiform region than controls and relatives. Our finding of greater thickness in adult biological relatives could represent a maladaptive abnormality or alternatively, a compensatory mechanism. Previous literature suggests that the nature of abnormalities in relatives can vary by the age of relatives and change across the developmental period. Abnormalities in patients may depend on lifestyle factors and on current and previous anti-psychotic medication use. Our results speak to the need to study various populations of patients and relatives across the lifespan to better understand different developmental periods and the impact of environmental factors. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 07/2015; DOI:10.1002/ajmg.b.32354 · 3.42 Impact Factor
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    • "This was consistent with other studies of similar patient groups and involving thinning of fronto-temporal-parietal cortical regions [25,26]. Widespread cortical thinning involving frontal, temporal and parietal regions were found in patients with chronic schizophrenia, highlighting that schizophrenia is associated with a potential neurodevelopmental deficits involving disruption of cortical maturation [27,28]. In addition, these changes in cortical thickness have been found to progress over time [29,30]. "
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    ABSTRACT: Although the genome wide supported psychosis susceptibility neurogranin (NRGN) gene is expressed in human brains, it is unclear how it impacts brain morphology in schizophrenia. We investigated the influence of NRGN rs12807809 on cortical thickness, subcortical volumes and shapes in patients with schizophrenia. One hundred and fifty six subjects (91 patients with schizophrenia and 65 healthy controls) underwent structural MRI scans and their blood samples were genotyped. A brain mapping algorithm, large deformation diffeomorphic metric mapping, was used to perform group analysis of subcortical shapes and cortical thickness. Patients with risk TT genotype were associated with widespread cortical thinning involving frontal, parietal and temporal cortices compared with controls with TT genotype. No volumetric difference in subcortical structures (hippocampus, thalamus, amygdala, basal ganglia) was observed between risk TT genotype in patients and controls. However, patients with risk TT genotype were associated with thalamic shape abnormalities involving regions related to pulvinar and medial dorsal nuclei. Our results revealed the influence of the NRGN gene on thalamocortical morphology in schizophrenia involving widespread cortical thinning and thalamic shape abnormalities. These findings help to clarify underlying NRGN mediated pathophysiological mechanisms involving cortical-subcortical brain networks in schizophrenia.
    PLoS ONE 12/2013; 8(12):e85603. DOI:10.1371/journal.pone.0085603 · 3.23 Impact Factor
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    • "in the psychopathology of schizophrenia, and involved in particular with the production of auditory hallucinations (Sun et al., 2009; Garcia-Marti et al., 2012; Oertel-Knöchel et al., 2013). "
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    ABSTRACT: Computational brain-imaging studies of individuals at familial high risk for psychosis have provided interesting results, but interpreting these findings can be a challenge due to a number of factors. We searched the literature for studies reporting whole brain voxel-based morphometry (VBM) or functional magnetic resonance imaging (fMRI) findings in people at familial high risk for schizophrenia compared with a control group. A voxel-wise meta-analysis with the effect-size version of Signed Differential Mapping (ES-SDM) identified regional abnormalities of functional brain response. Similarly, an ES-SDM meta-analysis was conducted on VBM studies. A multi-modal imaging meta-analysis was used to highlight brain regions with both structural and functional abnormalities. Nineteen studies met the inclusion criteria, in which a total of 815 familial high-risk individuals were compared to 685 controls. Our fMRI results revealed a number of regions of altered activation. VBM findings demonstrated both increases and decreases in grey matter density of relatives in a variety of brain regions. The multimodal analysis revealed relatives had decreased grey matter with hyper-activation in the left inferior frontal gyrus/amygdala, and decreased grey matter with hypo-activation in the thalamus. We found several regions of altered activation or structure in familial high-risk individuals. Reliable fMRI findings in the right posterior superior temporal gyrus further confirm that alteration in this area is a potential marker of risk.
    11/2013; 221(1). DOI:10.1016/j.pscychresns.2013.07.008
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