Psychometric Assessment of an Item Bank for Adaptive Testing on Patient-Reported Experience of Care Environment for Severe Mental Illness: Validation Study.

BACKGROUND: The care environment significantly influences the experiences of patients with severe mental illness and the quality of their care. While a welcoming and stimulating environment enhances patient satisfaction and health outcomes, psychiatric facilities often prioritize staff workflow over patient needs. Addressing these challenges is crucial to improving patient experiences and outcomes in mental health care. OBJECTIVE: This study is part of the Patient-Reported Experience Measure for Improving Quality of Care in Mental Health (PREMIUM) project and aims to establish an item bank (PREMIUM-CE) and to develop computerized adaptive tests (CATs) to measure the experience of the care environment of adult patients with schizophrenia, bipolar disorder, or major depressive disorder. METHODS: We performed psychometric analyses including assessments of item response theory (IRT) model assumptions, IRT model fit, differential item functioning (DIF), item bank validity, and CAT simulations. RESULTS: In this multicenter cross-sectional study, 498 patients were recruited from outpatient and inpatient settings. The final PREMIUM-CE 13-item bank was sufficiently unidimensional (root mean square error of approximation=0.082, 95% CI 0.067-0.097; comparative fit index=0.974; Tucker-Lewis index=0.968) and showed an adequate fit to the IRT model (infit mean square statistic ranging between 0.7 and 1.0). DIF analysis revealed no item biases according to gender, health care settings, diagnosis, or mode of study participation. PREMIUM-CE scores correlated strongly with satisfaction measures (r=0.69-0.78; P<.001) and weakly with quality-of-life measures (r=0.11-0.21; P<.001). CAT simulations showed a strong correlation (r=0.98) between CAT scores and those of the full item bank, and around 79.5% (396/498) of the participants obtained a reliable score with the administration of an average of 7 items. CONCLUSIONS: The PREMIUM-CE item bank and its CAT version have shown excellent psychometric properties, making them reliable measures for evaluating the patient experience of the care environment among adults with severe mental illness in both outpatient and inpatient settings. These measures are a valuable addition to the existing landscape of patient experience assessment, capturing what truly matters to patients and enhancing the understanding of their care experiences. TRIAL REGISTRATION: ClinicalTrials.gov NCT02491866; https://clinicaltrials.gov/study/NCT02491866.

Development of the PREMIUM computerized adaptive testing for measuring the access and care coordination for patients with severe mental illness.

Severe mental illness (SMI) patients often have complex health needs, which makes it difficult to access and coordinate their care. This study aimed to develop a computerized adaptive testing (CAT) tool, PREMIUM CAT-ACC, to measure SMI patients' experience with access and care coordination. This multicenter and cross-sectional study included 496 adult in- and out-patients with SMI (i.e., schizophrenia, bipolar disorder, or major depressive disorder). Psychometric analysis of the 13-item bank showed adequate properties, with preliminary evidence of external validity and no substantial differential item functioning for sex, age, care setting, and diagnosis, making it suitable for CAT administration. A post-hoc CAT simulation demonstrated that the tool was efficient and accurate, with an average of seven items, compared to the full item bank administration. Its use by clinicians can contribute to optimizing patient care pathways and transitioning towards more person-centered healthcare.

Correlation between assessment of cytochrome P450 1A2 activity and enzyme activity scores, and their relation to clozapine exposure.

AIMS: Cytochrome P450 1A2 (CYP1A2) is involved in the metabolism of antipsychotic drugs such as clozapine and olanzapine. Personalization of these treatments requires an accurate estimation of CYP1A2 activity. In this study, we aimed (1) to evaluate the correlation between activity score (AS), covariate-corrected activity score (CCS) and the phenotype of CYP1A2 using a caffeine test probe and (2) to investigate their relationship with dose-adjusted clozapine concentrations in a subgroup of the cohort. METHODS: A multicentric, retrospective and observational study was carried out in the French university hospitals of Marseille and Tours. CYP1A2 activity was calculated by the paraxanthine/caffeine (17X/137X) ratio determined 4 h after an oral intake of 100 mg caffeine. AS was calculated according to the CYP1A2*1F alleles. CCS was calculated according to the CYP1A2*1F alleles, smoking status and the presence of concomitant inhibitors. RESULTS: As expected, among the 89 patients included, the 17X/137X ratio was significantly higher in patients who smoked. We found a significant but modest correlation between the 17X/137X ratio and CCS (R2 = 0.3, P = 1.74 × 10-8 ) but none between the 17X/137X ratio and AS (R2 = -0.007, P = 0.52). AS was not correlated with dose-adjusted clozapine levels, contrary to CCS (R2 = 0.19, P = 0.016) and especially the 17X/137X ratio (R2 = 0.42, P = 1.7 × 10-5 ). CONCLUSIONS: Correlation with clozapine concentrations showed the advantage of the 17X/137X ratio over the CCS in clozapine dose optimization. CYP1A2 activity, especially when determined by the caffeine probe, may be used to personalize clozapine dosing for patients experiencing treatment failure.

Calibration and Validation of a PREMIUM-DT Item Bank to Measure the Experience of Drug Therapy for Patients with Severe Mental Illness.

The aim of this study was to (1) calibrate an item bank to measure patients' experience of drug therapy for adult patients with SMIs and (2) develop computerized adaptive testing (CAT) to improve its use in routine practice. This is a cross-sectional, multicentric study involving 541 patients with schizophrenia, bipolar disorder, and major depressive disorder. Analyses based on classical test and item response theories were performed. After 7 highly inter-correlated items and 4 items with low factor loadings were removed, the remaining 26 items were sufficiently unidimensional (RMSEA = 0.069, CFI = 0.969, TLI = 0.963) and showed adequate fit to the generalized partial credit model. There was no differential item functioning by gender, age, care setting, or diagnosis from moderate- to large-magnitude. The mean score was 46.0 ± 16.9 and was significantly higher for patients reporting good medication adherence. The resulting PREMIUM-DT item bank has strong psychometric properties, and CAT facilitates widespread use in clinical settings (an average of 8 items administered, corresponding to a reliability of >0.90). Our results suggest that practical information and information about the side effects of psychotropic treatments and how to cope with them should be targeted as a priority to improve patients' experience of drug therapy.

Development and Calibration of the PREMIUM Item Bank for Measuring Respect and Dignity for Patients with Severe Mental Illness.

Most patient-reported experience measures (PREMs) are paper-based, leading to a high burden for patients and care providers. The aim of this study was to (1) calibrate an item bank to measure patients' experience of respect and dignity for adult patients with serious mental illnesses and (2) develop computerized adaptive testing (CAT) to improve the use of this PREM in routine practice. Patients with schizophrenia, bipolar disorder, and major depressive disorder were enrolled in this multicenter and cross-sectional study. Psychometric analyses were based on classical test and item response theories and included evaluations of unidimensionality, local independence, and monotonicity; calibration and evaluation of model fit; analyses of differential item functioning (DIF); testing of external validity; and finally, CAT development. A total of 458 patients participated in the study. Of the 24 items, 2 highly inter-correlated items were deleted. Factor analysis showed that the remaining items met the unidimensional assumption (RMSEA = 0.054, CFI = 0.988, TLI = 0.986). DIF analyses revealed no biases by sex, age, care setting, or diagnosis. External validity testing has generally supported our assumptions. CAT showed satisfactory accuracy and precision. This work provides a more accurate and flexible measure of patients' experience of respect and dignity than that obtained from standard questionnaires.

Measuring the Patient Experience of Mental Health Care: A Systematic and Critical Review of Patient-Reported Experience Measures.

BACKGROUND: There is growing concern about measuring patient experience with mental health care. There are currently numerous patient-reported experience measures (PREMs) available for mental health care, but there is little guidance for selecting the most suitable instruments. The objective of this systematic review was to provide an overview of the psychometric properties and the content of available PREMs. METHODS: A comprehensive review following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines was conducted using the MEDLINE database with no date restrictions. The content of PREMs was analyzed using an inductive qualitative approach, and the methodological quality was assessed according to Pesudovs quality criteria. RESULTS: A total of 86 articles examining 75 PREMs and totaling 1932 items were included. Only four PREMs used statistical methods from item response theory (IRT). The 1932 items covered seven key mental health care domains: interpersonal relationships (22.6%), followed by respect and dignity (19.3%), access and care coordination (14.9%), drug therapy (14.1%), information (9.6%), psychological care (6.8%) and care environment (6.1%). Additionally, a few items focused on patient satisfaction (6.7%) rather than patient experience. No instrument covered the latent trait continuum of patient experience, as defined by the inductive qualitative approach, and the psychometric properties of the instruments were heterogeneous. CONCLUSION: This work is a critical step in the creation of an item library to measure mental health care patient-reported experience that will be used in France to develop, validate, and standardize item banks and computerized adaptive testing (CAT) based on IRT. It will also provide internationally replicable measures that will allow direct comparisons of mental health care systems. TRIAL REGISTRATION: NCT02491866.

Posttraumatic Stress Disorder is associated with altered reward mechanisms during the anticipation and the outcome of monetary incentive cues.

BACKGROUND: Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. METHODS: Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. RESULTS: During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p < 0.05 family-wise error (FWE)-corrected), while TECs had specific activation in the anterior cingulate cortex. When obtaining monetary gains, PTSD patients had specific activation in the caudate nucleus, while TECs had specific activations in the right hypothalamus, subthalamic nucleus, and left inferior frontal gyrus. CONCLUSION: For the first time, functional brain activation during both the anticipation and the outcome of monetary rewards is reported altered in PTSD patients. These alterations might be associated with the complex symptomatology of PTSD.

The Patient-Reported Experience Measure for Improving qUality of care in Mental health (PREMIUM) project in France: study protocol for the development and implementation strategy.

BACKGROUND: Measuring the quality and performance of health care is a major challenge in improving the efficiency of a health system. Patient experience is one important measure of the quality of health care, and the use of patient-reported experience measures (PREMs) is recommended. The aims of this project are 1) to develop item banks of PREMs that assess the quality of health care for adult patients with psychiatric disorders (schizophrenia, bipolar disorder, and depression) and to validate computerized adaptive testing (CAT) to support the routine use of PREMs; and 2) to analyze the implementation and acceptability of the CAT among patients, professionals, and health authorities. METHODS: This multicenter and cross-sectional study is based on a mixed method approach, integrating qualitative and quantitative methodologies in two main phases: 1) item bank and CAT development based on a standardized procedure, including conceptual work and definition of the domain mapping, item selection, calibration of the item bank and CAT simulations to elaborate the administration algorithm, and CAT validation; and 2) a qualitative study exploring the implementation and acceptability of the CAT among patients, professionals, and health authorities. DISCUSSION: The development of a set of PREMs on quality of care in mental health that overcomes the limitations of previous works (ie, allowing national comparisons regardless of the characteristics of patients and care and based on modern testing using item banks and CAT) could help health care professionals and health system policymakers to identify strategies to improve the quality and efficiency of mental health care. TRIAL REGISTRATION: NCT02491866.

Fear extinction learning improvement in PTSD after EMDR therapy: an fMRI study.

Objective: Neurobiological models of Posttraumatic Stress Disorder (PTSD) implicate fear processing impairments in the maintenance of the disorder. Eye Movement Desensitization and Reprocessing (EMDR) is one of the most efficient psychotherapies to treat PTSD. We aimed at exploring the brain mechanisms of the fear circuitry involved in PTSD patients' symptom remission after EMDR therapy. Method: Thirty-six PTSD participants were randomly assigned to either EMDR group receiving EMDR therapy or Wait-List (WL) group receiving supportive therapy. Participants underwent a behavioural fear conditioning and extinction paradigm during functional magnetic resonance (fMRI). In the EMDR group, patients were scanned at baseline, before EMDR and one week after remission. In the WL group, patients were scanned at baseline and within the same time interval as the EMDR group. Results: In the EMDR group after treatment, fear responses in the late extinction were significantly lower than before therapy. In parallel, significant functional activity and connectivity changes were found in the EMDR group versus the WL during the late extinction. These changes involve the fear circuit (amygdalae, left hippocampus), the right inferior frontal gyrus, the right frontal eye field and insula (pFWE < .05). Conclusion: These functional modifications underlie a significant improvement of fear extinction learning in PTSD patients after EMDR therapy.

Objetivo: Los modelos neurobiológicos del TEPT implican deficiencias en el procesamiento del miedo en el mantenimiento del trastorno. EMDR es una de las psicoterapias más eficaces para tratar el TEPT. Nuestro objetivo fue explorar los mecanismos cerebrales de los circuitos de miedo implicados en la remisión de los síntomas de los pacientes con el TEPT después de la terapia EMDR.Método: Treinta y seis participantes con el TEPT fueron asignados aleatoriamente a un grupo EMDR que recibió terapia EMDR o un grupo de Lista de Espera (LE) que recibió terapia de apoyo. Los participantes se sometieron a un paradigma de condicionamiento y extinción del miedo conductual durante la resonancia magnética funcional (fMRI). En el grupo EMDR, los pacientes fueron escaneados al inicio del estudio, antes de EMDR y una semana después de la remisión. En el grupo LE, los pacientes fueron escaneados al inicio y en el mismo intervalo de tiempo que el grupo EMDR.Resultados: En el grupo EMDR después del tratamiento, las respuestas de miedo en la extinción tardía fueron significativamente más bajas que antes de la terapia. En paralelo, se encontraron cambios significativos en la actividad funcional y en la conectividad en el grupo EMDR v/s el grupo LE durante la extinción tardía. Estos cambios involucran el circuito de miedo (amígdala, hipocampo izquierdo), el giro frontal inferior derecho, los campos del ojo frontal derecho y la ínsula (pFWE < .05).Conclusión: Estas modificaciones funcionales subyacen a una mejora significativa del aprendizaje de extinción del miedo en pacientes con el TEPT después de la terapia EMDR.

Patients' satisfaction with hospital health care: Identifying indicators for people with severe mental disorder.

BACKGROUND: Patients' perception of psychiatric healthcare is a critical indicator in measuring service quality. The aim of the study was to determine patient's level of satisfaction with the quality of health care delivered at the inpatient departments, and to identify the service quality factors that were important to patients. METHOD: The Satisfaction with Psychiatry Care Questionnaire-22 was administered to 125 consecutive inpatients with schizophrenia or schizoaffective disorder in a stable condition. Sociodemographic and background variables, illness and symptom severity, insight, social anhedonia, self-esteem, perceived social support, and satisfaction with quality of life were collected. RESULTS: Although the participants generally expressed satisfaction with the inpatient services, they indicated that the weakest aspects of the service were in the domains of 'personal experience', 'information' and 'activity'. Women were significantly more dissatisfied than men with 'staff', 'care', and by general satisfaction. Multiple regression analysis revealed that satisfaction with hospital health care was associated with five indicators: insight, satisfaction with physical health, self-efficacy, family support, and social anhedonia. CONCLUSION: Personality related factors rather than psychopathological symptoms were associated with a satisfaction with care of admitted patients with severe mental illness. These factors could be targets for interventions aimed to improve treatment and hospital services.

Assessment of health needs, satisfaction with care, and quality of life in compulsorily admitted patients with severe mental disorders.

This cross-sectional study compared the levels of needs, care satisfaction, quality of life, and social support of compulsory admitted patients with severe mental disorders to a comparable group of voluntary admitted patients. One hundred and twenty-five patients with schizophrenia and schizoaffective disorder were admitted to a hospital by district psychiatrist order (DPO), court observation order (COO), or voluntary (VA). Participants were assessed before discharge using questionnaires, and psychiatric rating scales. A linear discriminant analysis revealed eight variables that best differentiated the three groups. COO patients were significantly discriminated from the two other groups (DPO and VA) by severe negative symptoms, better satisfaction with both nursing staff and family support. COO subjects had more non-illness unmet needs, while reported better hedonic capacity for social and interpersonal pleasure - compared to VA patients. DPO patients were significantly indicated by poorer awareness to illness, but better satisfaction with subjective feelings. VA subjects were significantly discriminated from compulsory admitted patients by higher illness severity scores. Assessment of unmet needs, satisfaction with care, quality of life, hedonic capacity, and social support constitute the factors that differentiate compulsory admitted patients and could be targets for interventions aimed to reduce the negative effects of compulsory admissions.

Serotonin transporter gene expression predicts the worsening of suicidal ideation and suicide attempts along a long-term follow-up of a Major Depressive Episode.

The quest for biomarkers in suicidal behaviors has been elusive so far, despite their potential utility in clinical practice. One of the most robust biological findings in suicidal behaviors is the alteration of the serotonin transporter function in suicidal individuals. Our main objective was to investigate the predictive value of the serotonin transporter gene expression (SLC6A4) for suicidal ideation and as secondary, for suicide attempts in individuals with a major depressive episode (MDE). A 30-week prospective study was conducted on 148 patients with a MDE and 100 healthy controls including 4 evaluation times (0, 2, 8 and 30 weeks). Blood samples and clinical data were collected and SLC6A4 mRNA levels were measured from peripheral blood mononuclear cells using RT-qPCR. We first demonstrated the stability and reproducibility of SLC6A4 mRNA expression measures over time in healthy controls (F=0.658; p=0.579; η2=0.008; ICC=0.91, 95% CI [0.87-0.94]). Baseline SLC6A4 expression level (OR=0.563 [0.340-0.932], p=0.026) as well as early changes in SLC6A4 expression between baseline and the 2nd week (ß=0.200, p=0.042) predicted the worsening of suicidal ideation (WSI) in the following 8 weeks. Moreover, changes in SLC6A4 expression between the 2nd and 8th weeks predicted the occurrence of a suicide attempt within 30 weeks (OR=10.976 [1.438-83.768], p=0.021). Altogether, the baseline level and the changes in SLC6A4 mRNA expression during a MDE might predict the WSI and the occurrence of suicidal attempts and could be a useful biomarker in clinical practice.

Impaired cortico-limbic functional connectivity in schizophrenia patients during emotion processing.

Functional dysconnection is increasingly recognized as a core pathological feature in schizophrenia. Aberrant interactions between regions of the cortico-limbic circuit may underpin the abnormal emotional processing associated with this illness. We used a functional magnetic resonance imaging (fMRI) paradigm designed to dissociate the various components of the cortico-limbic circuit (i.e. a ventral automatic circuit that is intertwined with a dorsal cognitive circuit), in order to explore bottom-up appraisal as well as top-down control during emotion processing. In schizophrenia patients compared to healthy controls, bottom-up processes were associated with reduced interaction between the amygdala and both the anterior cingulate cortex (ACC) and the dorsolateral prefrontal cortex (DLPFC). Contrariwise, top-down control processes led to stronger connectivity between the ventral affective and the dorsal cognitive circuits, i.e. heightened interactions between the ventral ACC and the DLPFC as well as between dorsal and ventral ACC. These findings offer a comprehensive view of the cortico-limbic dysfunction in schizophrenia. They confirm previous results of impaired propagation of information between the amygdala and the prefrontal cortex and suggest a defective functional segregation in the dorsal cognitive part of the cortico-limbic circuit.

Modeling a linkage between blood transcriptional expression and activity in brain regions to infer the phenotype of schizophrenia patients.

Hundreds of genetic loci participate to schizophrenia liability. It is also known that impaired cerebral connectivity is directly related to the cognitive and affective disturbances in schizophrenia. How genetic susceptibility and brain neural networks interact to specify a pathological phenotype in schizophrenia remains elusive. Imaging genetics, highlighting brain variations, has proven effective to establish links between vulnerability loci and associated clinical traits. As previous imaging genetics works in schizophrenia have essentially focused on structural DNA variants, these findings could be blurred by epigenetic mechanisms taking place during gene expression. We explored the meaningful links between genetic data from peripheral blood tissues on one hand, and regional brain reactivity to emotion task assayed by blood oxygen level-dependent functional magnetic resonance imaging on the other hand, in schizophrenia patients and matched healthy volunteers. We applied Sparse Generalized Canonical Correlation Analysis to identify joint signals between two blocks of variables: (i) the transcriptional expression of 33 candidate genes, and (ii) the blood oxygen level-dependent activity in 16 region of interest. Results suggested that peripheral transcriptional expression is related to brain imaging variations through a sequential pathway, ending with the schizophrenia phenotype. Generalization of such an approach to larger data sets should thus help in outlining the pathways involved in psychiatric illnesses such as schizophrenia. IMAGING: SEARCHING FOR LINKS TO AID DIAGNOSIS: Researchers explore links between the expression of genes associated with schizophrenia in blood cells and variations in brain activity during emotion processing. El Chérif Ibrahim and Eric Fakra at Aix-Marseille Université, France, and colleagues have developed a method to relate the expression levels of 33 schizophrenia susceptibility genes in blood cells and functional magnetic resonance imaging (fMRI) data obtained as individuals carry out a task that triggers emotional responses. Although they found no significant differences in the expression of genes between the 26 patients with schizophrenia and 26 healthy controls they examined, variations in activity in the superior temporal gyrus were strongly linked to schizophrenia-associated gene expression and presence of disease. Similar analyses of larger data sets will shed further light on the relationship between peripheral molecular changes and disease-related behaviors and ultimately, aid the diagnosis of neuropsychiatric disease.

[Benefit of mortality and morbidity reviews in psychiatry]. / Intérêt des revues de mortalité et de morbidité en psychiatrie.

A mortality and morbidity (M&M) review consists in analysing, collectively and retrospectively, the cases of patients whose evolution has been marked by a complication or death. This analysis must question whether such an outcome could have been avoided, making it possible to identify the causes and correct the factors having contributed to its occurrence. After a presentation of the methodological and organisational principles, as well as the M&M reviews carried out in France, attention is turned to those performed in psychiatry and identifying the main perspectives for the discipline.

Grey matter density changes of structures involved in Posttraumatic Stress Disorder (PTSD) after recovery following Eye Movement Desensitization and Reprocessing (EMDR) therapy.

Recovery of stress-induced structural alterations in Posttraumatic Stress Disorder (PTSD) remains largely unexplored. This study aimed to determine whether symptoms improvement is associated with grey matter (GM) density changes of brain structures involved in PTSD. Two groups of PTSD patients were involved in this study. The first group was treated with Eye Movement Desensitization and Reprocessing (EMDR) therapy and recovered from their symptoms (recovery group) (n = 11); Patients were scanned prior to therapy (T1), one week (T2) and five months after the end of therapy (T3). The second group included patients which followed a supportive therapy and remained symptomatic (wait-list group) (n = 7). They were scanned at three time-steps mimicking the same inter-scan intervals. Voxel-based morphometry (VBM) was used to characterize GM density evolution. GM density values showed a significant group-by-time interaction effect between T1 and T3 in prefrontal cortex areas. These interaction effects were driven by a GM density increase in the recovery group with respect to the wait-list group. Symptoms removal goes hand-in-hand with GM density enhancement of structures involved in emotional regulation.

Psychometric properties of the Ruminative Response Scale-short form in a clinical sample of patients with major depressive disorder.

BACKGROUND: The Ruminative Response Scale (RRS)-short form is one of the most widely used measures of rumination, comprising ten items and two components: reflection and brooding. The aim of this study was to investigate RRS validity and reliability in a clinical sample of French patients with major depressive disorder (MDD). SUBJECTS AND METHODS: Outpatients with a DSM-IV-TR diagnosis of MDD were recruited from a public academic hospital in France. Depressive symptoms were evaluated by the Beck Depression Inventory, anxiety by the State-Trait Anxiety Inventory - state scale, and quality of life by the 36-Item Short Form Health Survey (SF-36) questionnaire. Confirmatory factor analyses, item-dimension correlations, Cronbach's α-coefficients, Rasch statistics, and external validity were tested. Differential item functioning analyses were performed for sex. RESULTS: A total of 109 patients participated. The final reflection-brooding two-factor model of the RRS showed a good fit (root-mean-square error of approximation 0.041, comparative fit index 0.987, standardized root-mean-square residual 0.048) after removing one item (daily diary writing). Internal item consistency and reliability were satisfactory for the two dimensions. External validity testing confirmed that RRS scores were correlated with Beck Depression Inventory, State-Trait Anxiety Inventory, and SF-36 scores. There was no differential item functioning across sexes. CONCLUSION: These results demonstrated good scale reliability and validity for assessing rumination in patients with MDD.

Caregiver's quality of life and its positive impact on symptomatology and quality of life of patients with schizophrenia.

BACKGROUND: Although the quality of life (QoL) experienced by patients with schizophrenia has been recognized, few studies have assessed the relationship between the caregivers' QoL and patients' QoL. METHODS: The study included 253 stabilized outpatients with schizophrenia and their caregivers from 3 Mental Health Services in Bolivia (N = 83), Chile (N = 85) and Peru (N = 85). Caregivers' and patients' QoL were respectively assessed using two specific QoL questionnaires (S-CGQoL and S-QoL 18). We collected socio-demographic information and clinical data. Multiple linear regressions were performed to determine which variables were associated with patient's QoL. We tested the following hypothesis using structural equation modeling (SEM): caregivers' QoL may have an indirect effect on patients' QoL mediated by their influence of the severity of psychotic symptoms. RESULTS: In the multivariate analysis, the caregivers' QoL was not significantly associated with the patients' QoL, except for one QoL dimension about relationship with family (Beta = 0.23). Among patients' characteristics, being a woman and Aymara, having lower educational level, unemployment and severity of symptoms was significantly associated to a lower QoL. The SEM revealed a moderate significant association between caregivers' QoL and psychotic symptoms severity (path coefficient = -0.32) and a significant association between psychotic symptoms severity and patients QoL (path coefficient = -0.40). The indirect effect of caregivers' QoL on patients' QoL was significant (mediated effect coefficient = 0.13). CONCLUSION: Improvement of caregiver's QoL may have a direct impact on the psychotic symptoms of patients and indirectly on patient's QoL, confirming the need for ongoing family interventions in these regions.

Childhood trauma and emotional processing circuits in schizophrenia: A functional connectivity study.

Childhood trauma strongly impacts emotional responses in schizophrenia. We have explored an association between early trauma and the amygdala functional connectivity using generalized psychophysiological interaction during an emotional task. Twenty-one schizophrenia patients and twenty-five controls were included. In schizophrenia patients, higher levels of sexual abuse and physical neglect during childhood were associated with decreased connectivity between the amygdala and the posterior cingulate/precuneus region. Additionally, patients showed decreased coupling between the amygdala and the posterior cingulate/precuneus region compared to controls. These findings suggest that early trauma could impact later connectivity in specific stress-related circuits affecting self-consciousness and social cognition in schizophrenia.

How to: Measuring blood cytokines in biological psychiatry using commercially available multiplex immunoassays.

Cytokines produced by both immune and non-immune cells are likely to play roles in the development and/or progression of psychiatric disorders. Indeed, many investigators have compared the blood cytokine levels in psychiatric patients with those of healthy controls or monitored their levels in patients during disease progression to identify biomarkers. Nevertheless, very few studies have confirmed that such cytokines remain stable in healthy individuals through periods of weeks and months. This is an important issue to consider before using blood cytokine levels as biomarkers of disease traits, disease state, or treatment response. Although multiplex assay technology represents an advance in identifying biomarkers because it allows simultaneous examination of large panels of analytes from a small volume of sample, it is necessary to verify whether these assays yield enough sensitivity and reproducibility when applied to the blood from neuropsychiatric patients. Therefore, we compared two multiplex immunoassays, the bead-based Luminex® (Bio-Rad) and the electro-chemiluminescence-based V-plex® (MesoScaleDiscovery), for the detection and quantification of 31 cytokines, chemokines and growth factors in both the sera and plasma of patients with major depressive episodes (MDE) and age- and sex-matched healthy control subjects during a 30-week period. Although both platforms exhibited low coefficients of variability (CV) between the duplicates in the calibration curves, the linearity was better in general for the V-PLEX® platform. However, neither platform was able to detect the absolute values for all of the tested analytes. Among the 16 analytes that were detected by both assays, the intra-assay reproducibility was in general better with the V-PLEX® platform. Although it is not a general rule that the results from sera and plasma will be correlated, consistent results were more frequent with the V-PLEX® platform. Furthermore, the V-PLEX® results were more consistent with the gold standard ELISA simplex assay for IL-6 in both sera and plasma. The intra-individual variability of the measurements, among the sera and plasma for the 4 samples harvested from each healthy individual, was low for Eotaxin, G-CSF, IL-4, IL-7, IL-9, IL-12p40, IL-12p70, IL-15, MIP-1ß, PDGF-BB, TNF, TNF-ß and VEGF, but intermediate or high for IFN-γ, IL-6, IL-8, IL-10, and IP10. Together, these data suggest that extreme caution is needed in translating the results of multiplex cytokine profiling into biomarker discovery in psychiatry.