Cingulate Volume Abnormalities in Emerging Psychosis
Department of Psychiatry, c/o University Hospital Basel, University of Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Current pharmaceutical design
(Impact Factor: 3.45).
02/2012; 18(4):495-504. DOI: 10.2174/138161212799316316
Neuroanatomical abnormalities, including cingulate cortex volume abnormalities, are a common feature in psychosis. However, the extent to which these are related to a vulnerability to psychosis, as opposed to the disorder per se, is less certain. AIM UND HYPOTHESES: The aim of the present study is to compare cingulate gray matter volumes in different stages of psychosis. We reviewed previous studies of subjects in a prodromal stage of psychosis and tested cingulate volume changes during the transition to psychosis.
A cross-sectional MRI study of manually traced cingulate gray-matter volumes in 37 individuals with an at risk mental state (ARMS) for psychosis, 23 individuals with a first-episode psychosis (FEP), and 22 healthy controls (HC) was performed using a 1.5 T MRI-scanner. 16 of 37 ARMS individuals (43 %) developed psychosis during follow up (ARMS-T), whereas 21 did not (ARMS-NT). The mean duration of follow up in ARMS was 25.1 months. 8 cingulate subregions were analysed in a region-of-interest analysis.
Compared to HC, subjects with an ARMS had significantly reduced left caudal anterior cingulate cortex volume (p < 0.027). This finding was also evident at a trend level (p: 0.069) in FEP patients. Within ARMS, the ARMS-T group showed a significantly reduced whole right cingulate cortex (p: 0.036), right subgenual cingulate cortex (p: 0.036) and right posterior cingulate cortex (p: 0.012) compared to ARMS-NT.
These results suggest that the at risk mental state is associated with cingulate volume reductions, in particular in the left caudal anterior cingulate cortex (CACC). These abnormalities do not only seem to occur with transition to psychosis, but may be a correlate of an increased vulnerability to psychosis.
Available from: Stefan Borgwardt
- "Cross-sectional studies indicate that, relative to healthy controls, UHR subjects have reduced grey matter (GM) volume in frontal (Meisenzahl et al.
2008; Mechelli et al.
2011), lateral and medial temporal regions (Meisenzahl et al.
2008). Studies that used a region of interest (ROI) approach reported GM volume increases (Buehlmann et al.
2010) but also reductions (Phillips et al.
2002) in the hippocampus, reductions in the planum polare/temporale, insula and superior temporal gyrus (Takahashi et al.
2009, 2010), increases in the pituitary volume (Büschlen et al.
2011), and reductions in the anterior cingulate cortex (ACC) (Röthlisberger et al.
2012) in the UHR group compared with healthy controls. "
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Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis.
We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness.
At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not.
These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.
Available from: Stefania Tognin
- "In whole-brain voxel-based morphometry (VBM) studies, UHR-T relative to UHR-NT subjects showed reduced gray matter (GM) volume of the inferior frontal cortex, medial and lateral temporal, anterior cingulate cortex (ACC), insular, inferior and superior frontal cortices (2), and reduced GM density of the left temporal lobe and right cerebellum (3). In addition, VBM studies employing a region of interest (ROI) approach indicated that individuals who subsequently make transition to psychosis show reduced volume in the left parahippocampal gyrus (4), the bilateral insula (5) and the left ACC (6), and increased volume of the pituitary gland (7, 8) and the hippocampus (9). A recent VBM investigation has also shown that, in individuals at UHR for psychosis, lower scores on a semantic fluency task are associated with reduced GM density in a distributed network including the right superior/middle temporal gyrus, the right insula, and the left ACC, suggesting that the combination of these two types of data could inform outcome prediction in this population (10). "
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ABSTRACT: Neuroimaging holds the promise that it may one day aid the clinical assessment of individual psychiatric patients. However, the vast majority of studies published so far have been based on average differences between groups, which do not permit accurate inferences at the level of the individual. We examined the potential of structural Magnetic Resonance Imaging (MRI) data for making accurate quantitative predictions about symptom progression in individuals at ultra-high risk for developing psychosis. Forty people at ultra-high risk for psychosis were scanned using structural MRI at first clinical presentation and assessed over a period of 2 years using the Positive and Negative Syndrome Scale. Using a multivariate machine learning method known as relevance vector regression (RVR), we examined the relationship between brain structure at first clinical presentation, characterized in terms of gray matter (GM) volume and cortical thickness (CT), and symptom progression at 2-year follow-up. The application of RVR to whole-brain CT MRI data allowed quantitative prediction of clinical scores with statistically significant accuracy (correlation = 0.34, p = 0.026; Mean Squared-Error = 249.63, p = 0.024). This prediction was informed by regions traditionally associated with schizophrenia, namely the right lateral and medial temporal cortex and the left insular cortex. In contrast, the application of RVR to GM volume did not allow prediction of symptom progression with statistically significant accuracy. These results provide proof-of-concept that it could be possible to use structural MRI to inform quantitative prediction of symptom progression in individuals at ultra-high risk of developing psychosis. This would enable clinicians to target those individuals at greatest need of preventative interventions thereby resulting in a more efficient use of health care resources.
Available from: Alice Egerton
- "Our finding is broadly consistent with the numerous reports of abnormalities in the anterior cingulate cortex in early psychosis. For example, structural abnormalities in this area are present at onset of psychosis and may be predictive of conversion to psychosis in those at high risk of developing the disorder (Borgwardt et al, 2007; Dazzan et al, 2011; Fornito et al, 2008; Pantelis et al, 2003; Rothlisberger et al, 2012; Fusar-Poli et al, 2011). Moreover, functional magnetic resonance imaging studies show that antipsychotic treatment may be particularly effective in normalizing activity in the anterior cingulate cortex ((Snitz et al, 2005) and see (Karch et al, 2012) for review). "
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ABSTRACT: Many patients with schizophrenia show a limited symptomatic response to treatment with dopaminergic antipsychotics. This may reflect the additional involvement of non-dopaminergic neurochemical dysfunction in the pathophysiology of the disorder. We tested the hypothesis that brain glutamate levels would differ between patients with first-episode psychosis who were symptomatic compared with those with minimal symptoms following antipsychotic treatment. Proton magnetic resonance spectroscopy (1H-MRS) spectra were acquired at 3 Tesla in the anterior cingulate cortex and left thalamus in 15 patients with first-episode psychosis in symptomatic remission, and 17 patients with first-episode psychosis who were still symptomatic following at least one course of antipsychotic treatment. Metabolite levels were estimated in ratio to creatine (Cr) using LCModel. Levels of glutamate/Cr in the anterior cingulate cortex were significantly higher in patients who were still symptomatic than in those in remission (T(30)=3.02; P=0.005). Across the entire sample, higher levels of glutamate/Cr in the anterior cingulate cortex were associated with a greater severity of negative symptoms (r=0.42; P=0.017) and a lower level of global functioning (r=-0.47; P=0.007). These findings suggest that clinical status following antipsychotic treatment in schizophrenia is linked to glutamate dysfunction. Treatment with compounds acting on the glutamatergic system might therefore be beneficial in patients who respond poorly to dopaminergic antipsychotics.
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