Raphaëlle Richieri

Predictive value of brain perfusion SPECT for rTMS response in pharmacoresistant depression

PurposeThe aim of this study was to determine the predictive value of whole-brain voxel-based regional cerebral blood flow (rCBF) for repetitive transcranial magnetic stimulation (rTMS) response in patients with pharmacoresistant depression.MethodsThirty-three right-handed patients who met DSM-IV criteria for major depressive disorder (unipolar or bipolar depression) were included before rTMS. rTMS response was defined as at least 50% reduction in the baseline Beck Depression Inventory scores. The predictive value of 99mTc-ethyl cysteinate dimer (ECD) single photon emission computed tomography (SPECT) for rTMS response was studied before treatment by comparing rTMS responders to non-responders at voxel level using Statistical Parametric Mapping (SPM) (p < 0.001, uncorrected).ResultsOf the patients, 18 (54.5%) were responders to rTMS and 15 were non-responders (45.5%). There were no statistically significant differences in demographic and clinical characteristics (p > 0.10). In comparison to responders, non-responders showed significant hypoperfusions (p < 0.001, uncorrected) in the left medial and bilateral superior frontal cortices (BA10), the left uncus/parahippocampal cortex (BA20/BA35) and the right thalamus. The area under the curve for the combination of SPECT clusters to predict rTMS response was 0.89 (p < 0.001). Sensitivity, specificity, positive predictive value and negative predictive value for the combination of clusters were: 94, 73, 81 and 92%, respectively.ConclusionThis study shows that, in pharmacoresistant depression, pretreatment rCBF of specific brain regions is a strong predictor for response to rTMS in patients with homogeneous demographic/clinical features.

Risk factors for treatment resistance in unipolar depression: A systematic review

BACKGROUND Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression. METHODS The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments. RESULTS Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression. LIMITATIONS Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies. CONCLUSION Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

The Schizophrenia Caregiver Quality of Life questionnaire (S-CGQoL): Development and validation of an instrument to measure quality of life of caregivers of individuals with schizophrenia

OBJECTIVE This study aims to validate a self-administered, multidimensional QoL instrument based on the point of view of caregivers of individuals with schizophrenia. METHODS Data were collected through the departments of six psychiatric hospitals in France (n=246). The item reduction and validation processes were based on both item response theory and classical test theory. RESULTS The S-CGQoL contains 25 items describing seven dimensions (Psychological and Physical Well-Being; Psychological Burden and Daily Life; Relationships with Spouse; Relationships with Psychiatric Team; Relationships with Family; Relationships with Friends; and Material Burden). The seven-factor structure accounted for 74.4% of the total variance. Internal consistency was satisfactory; Cronbachs alpha coefficients ranged from 0.79 to 0.92 in the whole sample. The scalability was satisfactory, with INFIT statistics falling within an acceptable range. In addition, the results confirmed the absence of DIF and supported the invariance of the item calibrations. CONCLUSION The S-CGQoL is a self-administered QoL instrument that presents satisfactory psychometric properties and can be completed in 5 min, thereby fulfilling the goal of brevity sought in research and clinical practice.

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.

Quality of life among caregivers of patients with schizophrenia: a cross-cultural comparison of Chilean and French families.

BackgroundTo our knowledge, no study has examined quality of life (QoL) among caregivers of individuals with schizophrenia between a developing and a developed country. The aim of this study was to assess QoL of the caregivers of individuals with schizophrenia in two countries characterized by different social, economic and cultural conditions, namely Chile and France.MethodsData were collected from public mental health outpatient services in Arica (Chile), and in Marseille (France). QoL was measured with the short-form health survey scale - 36 items (SF36). QoL of 41 Chilean caregivers was firstly compared with 245 French caregivers. Univariate and multivariate analyses using linear regression were then performed to determine variables potentially related to QoL scores.ResultsThe caregivers were primarily mothers in the two groups, but Chilean caregivers were younger, and lived more frequently with the individual with schizophrenia than French caregivers. The SF36 scores were globally low in the two groups, especially on the mental QoL scores. Chilean caregivers reported lower physical SF36 scores than French caregivers. In the multivariate analysis, being mother and Chilean caregivers were the most regular features associating to a lower QoL.ConclusionDespite differences between Chile and France, especially in terms of quality and quantity of mental health services and economic supports, caregivers’ QoL levels remain particularly low for both countries. Future support programmes should address the specific needs of caregivers.

Neurocognition, Insight and Medication Nonadherence in Schizophrenia: A Structural Equation Modeling Approach

Objective The aim of this study was to examine the complex relationships among neurocognition, insight and nonadherence in patients with schizophrenia. Methods Design: Cross-sectional study. Inclusion criteria: Diagnosis of schizophrenia according to the DSM-IV-TR criteria. Data collection: Neurocognition was assessed using a global approach that addressed memory, attention, and executive functions; insight was analyzed using the multidimensional ‘Scale to assess Unawareness of Mental Disorder;’ and nonadherence was measured using the multidimensional ‘Medication Adherence Rating Scale.’ Analysis: Structural equation modeling (SEM) was applied to examine the non-straightforward relationships among the following latent variables: neurocognition, ‘awareness of positive symptoms’ and ‘negative symptoms’, ‘awareness of mental disorder’ and nonadherence. Results One hundred and sixty-nine patients were enrolled. The final testing model showed good fit, with normed χ2 = 1.67, RMSEA = 0.063, CFI = 0.94, and SRMR = 0.092. The SEM revealed significant associations between (1) neurocognition and ‘awareness of symptoms,’ (2) ‘awareness of symptoms’ and ‘awareness of mental disorder’ and (3) ‘awareness of mental disorder’ and nonadherence, mainly in the ‘attitude toward taking medication’ dimension. In contrast, there were no significant links between neurocognition and nonadherence, neurocognition and ‘awareness of mental disorder,’ and ‘awareness of symptoms’ and nonadherence. Conclusions Our findings support the hypothesis that neurocognition influences ‘awareness of symptoms,’ which must be integrated into a higher level of insight (i.e., the ‘awareness of mental disorder’) to have an impact on nonadherence. These findings have important implications for the development of effective strategies to enhance medication adherence.

Maintenance transcranial magnetic stimulation reduces depression relapse: A propensity-adjusted analysis

BACKGROUND The effectiveness of repetitive transcranial magnetic stimulation (TMS) is well established while studies of maintenance TMS are lacking. We aim here to determine whether maintenance is associated to a decrease in the relapse rate of depression, following successful acute treatment. METHODS We enrolled 59 consecutive patients with pharmacoresistant depression who have responded (>50% decrease in symptom severity) up to 6 weeks of acute TMS treatment. These patients received either 20 weeks of maintenance TMS (n=37) or no additional TMS treatment (n=22). We performed propensity adjusted-analysis to examine the association between the relapse rate over this 20-week period and maintenance TMS. Propensity analysis eliminated differences in baseline characteristics between patient with and without maintenance TMS and approximated the conditions of random site-of-treatment assignment. RESULTS At 20 weeks, relapse rate was significantly different between the two groups (p=0.004, propensity analysis): 14 patients in the maintenance TMS group (37.8%) vs. 18 in the non-maintenance TMS group (81.8%), with an adjusted Hazard Ratio (HR)=0.288 (0.124-0.669). CONCLUSIONS Maintenance TMS was associated with a significantly lower relapse rate in patients with pharmacoresistant depression in routine practice among responders.

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.

Chronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset

OBJECTIVES Inflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery. METHOD Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L. RESULTS Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043). CONCLUSION Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ.

Association of metabolic syndrome and inflammation with neurocognition in patients with schizophrenia

The aim of this study is to assess the relationships of metabolic syndrome (MetS) and inflammation with neurocognition in schizophrenia. In this cross-sectional study, we included patients with diagnosis of schizophrenia according to the DSM-IV-TR criteria. We collected socio-demographic information, clinical characteristics, anthropometric measurements, blood tests, and neurocognition measures. A multivariate analysis using multiple linear regressions was performed to determine variables that are potentially associated with neurocognition. The analyses were repeated using MetS as a dichotomised variable (< and ≥ 3 MetS criteria), a continuous variable (number of MetS criteria present), and for each component of MetS. One hundred and sixty-eight outpatients participated in our study. The prevalence of MetS was 27.4%. An association was found between the number of MetS criteria present and cognitive impairment. Among the different components of MetS, hypertriglycerides and abdominal obesity were the only factors associated with cognitive impairment. Other factors, such as smoking and alcohol dependence or abuse, also revealed a significant relationship, whereas inflammation was not associated with cognitive impairment. In conclusion, our findings suggest that MetS, alcohol use and non-smoking status are associated with cognitive impairment. These findings may support complementary therapeutic approaches in cognitive remediation that lessen the severity of cognitive impairment in schizophrenia.