Catherine Faget-Agius

Schizophrenia with preserved insight is associated with increased perfusion of the precuneus

BACKGROUND Preserved insight into illness has been suggested to be predictive of outcome in patients with schizophrenia. We aimed to investigate the functional substrate underlying preserved insight in these patients. METHODS We recruited patients with paranoid schizophrenia and healthy controls matched for age and sex. Patients were grouped according to preserved or impaired insight into illness using the Scale to assess Unawareness of Mental Disorder (SUMD). Whole-brain technetium-99m ethyl cysteinate dimer single photon emission computed tomography regional cerebral blood flow was compared at the voxel level between the 2 groups using a statistical parametric map (voxel-level significance of p < 0.001, uncorrected; cluster level significance of p < 0.05, uncorrected). RESULTS We enrolled 31 right-handed patients with schizophrenia and 18 controls in our study. Twenty-one (67.7%) patients had preserved insight. The 2 groups did not differ significantly in demographic and clinical characteristics or in treatment. Compared with controls, the whole group of patients showed bilateral frontotemporal hypoperfusions, with no statistical difference between patients with preserved or impaired insight for these areas. Patients with preserved insight showed significantly increased perfusion of the bilateral precuneus relative to those with impaired insight. LIMITATIONS Patients with subtypes other than paranoid schizophrenia have to be investigated to assess whether involvement of the precuneus in patients with preserved insight can be identified across the full spectrum of subtypes and symptoms of schizophrenia. Moreover, our study concerned only the central dimension (awareness of mental disorder) of 1 scale (SUMD); other dimensions of insight could be studied. CONCLUSION Our results show that schizophrenia with preserved insight is associated with greater perfusion of the precuneus, a brain area known to be involved in self- consciousness, suggesting a compensatory mechanism of fronto-temporal impairment.

A structural equation modelling approach to explore the determinants of quality of life in schizophrenia.

OBJECTIVE This study aimed to analyse the relationships among psychotic symptoms, depression, neurocognition and functioning as determinants of quality of life (QoL) in patients with schizophrenia. METHODS In this cross-sectional study, we evaluated QoL with the Schizophrenia Quality of Life 18-item scale (S-QoL 18), neurocognition with multiple tests exploring memory, attention and executive functions, the severity of psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS), depression with the Calgary Depression Scale for Schizophrenia (CDSS) and functioning using the Functional Remission Of General Schizophrenia (FROGS) scale. We used Structural Equation Modelling (SEM) to describe the relationships among the severity of psychotic symptoms, depression, neurocognition, functioning and QoL. RESULTS Two hundred and seventy-one outpatients with schizophrenia participated in our study. SEM showed good fit with χ(2)/df=1.97, root mean square error of approximation=0.06, comparative fit index=0.93 and standardized root mean square residuals=0.05. This model revealed that depression was the most important feature associated with QoL, mainly for the self-esteem, autonomy and resilience dimensions (direct path coefficient=-0.46). The direct path between functioning and QoL was also significant (path coefficient=0.26). The severity of psychotic symptoms and neurocognitive impairment were weakly and indirectly associated with QoL via functioning (path coefficients=-0.18 and 0.04, respectively). CONCLUSIONS This study contributes to a better understanding of the determinants of QoL in schizophrenia. Our findings should be considered in developing effective strategies for improving QoL among this population.

Neurophysiological correlates of metabolic syndrome and cognitive impairment in schizophrenia: A structural equation modeling approach

OBJECTIVE We aimed to investigate the brain functional substrate underlying relationships between metabolic syndrome (MetS) and cognitive impairment in schizophrenia. METHODS In this cross-sectional study, we collected socio-demographic, clinical, anthropometric, blood, and cognition data and performed brain 99mTc-ECD-SPECT imaging of cerebral blood flow in patients with schizophrenia. Patients were grouped according to the absence or presence of MetS. Whole-brain perfusion SPECTs were compared at voxel level between these two groups, and voxel-wise interregional correlation was performed to compare functional connectivity (voxel level significance of p<0.005, uncorrected; p<0.05 for the cluster, uncorrected; using SPM8). A structural equation model (SEM) was applied to examine the relationships between brain perfusion, connectivity between brain areas, and cognition. RESULTS Of the 55 patients, 17 had MetS. They performed significantly worse than patients without MetS on tests of executive functions (processing speed p=0.005 for TMT-A; and reactive flexibility p=0.014 for TMT-B), attention (D2 attention task p=0.007), and memory (California Verbal Learning Test p=0.039). In comparison to patients without MetS, those with MetS exhibited significant hypoperfusion within the left orbital prefrontal cortex and greater functional connectivity from this left frontal cluster within the left insula and middle/superior frontal gyrus. SEM confirmed the effect on executive functions of brain hypoperfusion and of increased connectivity, suggesting possible compensatory networks in patients with MetS. CONCLUSION Our study identifies the brain functional impact of MetS on cognition, with orbital prefrontal impairment and possible compensatory networks.

Quality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study

Inflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94–0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55–11.07), higher body mass index (OR = 1.16, 95% CI = 1.06–1.28), higher Fagerström score (OR = 1.22, 95% CI = 1.01–1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia.

Validation of a functional remission threshold for the Functional Remission of General Schizophrenia (FROGS) scale

OBJECTIVE The aim of this study was to develop a functional remission threshold for the Functional Remission Of General Schizophrenia (FROGS) scale, and test its validity regarding clinical and quality of life outcomes. METHODS DESIGN Cross-sectional study. INCLUSION CRITERIA Schizophrenia according to DSM-IV-TR criteria. DATA COLLECTION Functioning was assessed using the FROGS and the Global Assessment of Functioning (GAF) scales; psychotic symptoms using the Positive and Negative Syndrome Scale; memory, attention, and executive functions were assessed using the California Verbal Learning Test, the D2 attention task, the Stroop color-word test, the verbal fluency test, the Trail Making Test A and B and the Wechsler Adult Intelligence Scale; and quality of life using the schizophrenia quality of life (S-QoL 18) scale. ANALYSIS A logistic regression analysis including the different dimensions of the FROGS was used to create a composite score to classify patients into remitted and non-remitted according a gold standard (cut-off: GAF>= 61). Receiver operating characteristics analyses were then performed to determine the area under the curve (AUC). RESULTS Of 137 patients enrolled, 26 were functionally remitted and 111 were not remitted according to GAF score. The AUC for the combination of the FROGSs dimensions to detect functional remission was 0.903 (p<0.001). Sensitivity and specificity for the combination of the FROGS dimensions using the Youden index were 88.5 [69.8; 97.6] and 81.1 [72.5; 87.9], respectively. Validity of this combination was satisfactory. Patients in functional remission had a lower severity of the disease, especially for PANSS negative (p<0.001) and general psychopathology (p<0.001) symptoms. Only two cognitive functions (i.e. fluency and episodic memory) were improved in remitted patients. Higher quality of life levels were globally associated with better functioning. CONCLUSIONS These findings provide for first accurate FROGS thresholds to detect functional remission in schizophrenia.

Neural substrate of quality of life in patients with schizophrenia: a magnetisation transfer imaging study.

The aim of this study was to investigate the neural substrate underlying quality of life (QoL) and to demonstrate the microstructural abnormalities associated with impaired QoL in a large sample of patients with schizophrenia, using magnetisation transfer imaging. A total of 81 right-handed men with a diagnosis of schizophrenia and 25 age- and sex-similar healthy controls were included and underwent a 3T MRI with magnetization transfer ratio (MTR) to detect microstructural abnormalities. Compared with healthy controls, patients with schizophrenia had grey matter (GM) decreased MTR values in the temporal lobe (BA21, BA37 and BA38), the bilateral insula, the occipital lobe (BA17, BA18 and BA19) and the cerebellum. Patients with impaired QoL had lower GM MTR values relative to patients with preserved QoL in the bilateral temporal pole (BA38), the bilateral insula, the secondary visual cortex (BA18), the vermis and the cerebellum. Significant correlations between MTR values and QoL scores (p < 0.005) were observed in the GM of patients in the right temporal pole (BA38), the bilateral insula, the vermis and the right cerebellum. Our study shows that QoL impairment in patients with schizophrenia is related to the microstructural changes in an extensive network, suggesting that QoL is a bio-psychosocial marker.

Determinants of brain SPECT perfusion and connectivity in treatment-resistant depression

This study aims to characterize and compare functional brain single photon emission tomography (SPECT) perfusion and connectivity in treatment-resistant depression (TRD) according to distinct demographic or clinical profiles (male vs. female; old vs. young; unipolar vs. bipolar) and to study their relationship to the severity and the duration of episode/illness. We retrospectively included 127 consecutive patients who met DSM-IV criteria for a nonpsychotic major TRD episode. All patients were studied using (99m)Tc-ethyl cysteinate dimer SPECT. Whole-brain, voxel-based, between-groups analyses were performed according to demographic and clinical data and in comparison to 37 healthy subjects. Voxel-wise interregional correlation was also performed to compare functional SPECT connectivity. Finally, relationships were searched for regarding severity and duration of episode/illness. The whole group of patients exhibited significant hypoperfusion within bilateral fronto-temporal, insular, and anterior cingulate cortices, as well as within the left caudate. Functional connectivity between left frontal and left cerebellar regions was higher in patients than in healthy subjects. Gender, age, and type of mood disorder did not influence these SPECT patterns. A significant relationship was found between brain SPECT perfusion and either duration or global severity of illness in particular frontal areas. Our data support the hypothesis of a shared SPECT pattern, whatever the profile of TRD, involving fronto-temporal regions and the cerebellum.

High C-reactive protein levels are associated with depressive symptoms in schizophrenia

BACKGROUND Depressive symptoms are frequently associated with schizophrenia symptoms. C - Reactive protein (CRP), a marker of chronic inflammation, had been found elevated in patients with schizophrenia and in patients with depressive symptoms. However, the association between CRP level and depressive symptoms has been poorly investigated in patients with schizophrenia. The only study conducted found an association between high CRP levels and antidepressant consumption, but not with depressive symptoms investigated with the Calgary Depression Rating Scale for Schizophrenia (CDSS). OBJECTIVES The aim of this study was to evaluate CRP levels and depressive symptoms in patients with schizophrenia, and to determine whether high CRP levels are associated with depressive symptoms and/or antidepressant consumption, independently of potential confounding factors, especially tobacco-smoking and metabolic syndrome. METHODS Three hundred and seven patients with schizophrenia were enrolled in this study (mean age = 35.74 years, 69.1% male gender). Depressive symptoms was investigated with the CDSS. Patients were classified in two groups: normal CRP level (≤ 3.0mg/L) and high CRP level (> 3.0mg/L). Current medication was recorded. RESULTS 124 subjects (40.4%) were classified in the high CRP level group. After adjusting for confounding factors, these patients were found to have higher CDSS scores than those with normal CRP levels in multivariate analyses (p = 0.035, OR = 1.067, 95% CI = 1.004-1.132). No significant association between CRP levels and antidepressants consumption was found. LIMITATIONS The size sample is relatively small. The cut-off point for high cardiovascular risk was used to define the two groups. CRP was the sole marker of inflammation in this study and was collected at only one time point. The design of this study is cross-sectional and there are no conclusions about the directionality of the association between depression and inflammation in schizophrenia. CONCLUSION This study found an association between high rates of CRP levels and depressive symptoms in patients with schizophrenia, but no association with antidepressant consumption. Further studies are needed to investigate the impact of inflammation in schizophrenia.

Functional brain substrate of quality of life in patients with schizophrenia: A brain SPECT multidimensional analysis.

The aim of this study was to investigate the functional brain substrate of quality of life (QoL) in patients with schizophrenia. Participants comprised 130 right-handed patients with schizophrenia who underwent whole-brain single photon emission computed tomography (SPECT) with (99m)Tc-labeled ethylcysteinate dimer ((99m)Tc-ECD) for exploring correlations of regional cerebral blood flow (rCBF) with the eight dimensions score of the Schizophrenia Quality of Life questionnaire (S-QoL 18). A significant positive correlation was found between the global index of the S-QoL 18 and rCBF in the right superior temporal sulcus and between psychological well-being dimension and rCBF in Brodmann area (BA)6, BA8, BA9, and BA10 and between self-esteem dimension and rCBF in striatum and between family relationship dimension and rCBF in BA1, BA2, BA3, BA4, BA8, BA22, BA40, BA42 and BA44 and between relationship with friends dimension and rCBF in BA44 and between physical well-being dimension and rCBF in parahippocampal gyrus, and finally between autonomy dimension and rCBF in cuneus and precuneus. A significant negative correlation was found between resilience dimension and rCBF in precuneus and between sentimental life dimension and rCBF in BA10. Our findings provide neural correlates of QoL. Brain regions involved in cognitions, emotional information processing and social cognition underlie the different QoL dimensions.

Structural and functional reorganization of working memory system during the first decade in schizophrenia. A cross-sectional study

INTRODUCTION Progressive atrophy occurs in brain regions involved in the working memory network along the schizophrenias course, but without parallel evolution of working memory impairment. We investigated the functional organization inside this network at different stages of the disease. METHODS Twenty-eight patients with schizophrenia (16 with long disease duration (>60 months) and 12 with short disease duration (<60 months)) and eleven healthy controls underwent structural and functional MRI during an n-back task to determine atrophy and activation patterns. RESULTS At similar n-back performances and relative to short disease duration patients, long disease duration patients activated more frontal temporal parietal and frontal network during 0-back and 1-back tasks respectively. n-back scores were correlated to atrophy in the frontal-temporal areas. DISCUSSION Functional reorganization in the working memory network may play a compensatory role during the first ten years of schizophrenia.