Remission of depression in patients with schizophrenia and comorbid major depressive disorder: results from the FACE-SZ cohort.

BACKGROUND: Major depressive disorder (MDD) is underdiagnosed and undertreated in schizophrenia, and has been strongly associated with impaired quality of life.AimsTo determine the prevalence and associated factors of MDD and unremitted MDD in schizophrenia, to compare treated and non-treated MDD. METHOD: Participants were included in the FondaMental Expert Centers for Schizophrenia and received a thorough clinical assessment. MDD was defined by a Calgary score ≥6. Non-remitted MDD was defined by current antidepressant treatment (unchanged for >8 weeks) and current Calgary score ≥6. RESULTS: 613 patients were included and 175 (28.5%) were identified with current MDD. MDD has been significantly associated with respectively paranoid delusion (odds ratio 1.8; P = 0.01), avolition (odds ratio 1.8; P = 0.02), blunted affect (odds ratio 1.7; P = 0.04) and benzodiazepine consumption (odds ratio 1.8; P = 0.02). Antidepressants were associated with lower depressive symptoms score (5.4 v. 9.5; P < 0.0001); however, 44.1% of treated patients remained in non-remittance MDD. Nonremitters were found to have more paranoid delusion (odds ratio 2.3; P = 0.009) and more current alcohol misuse disorder (odds ratio 4.8; P = 0.04). No antidepressant class or specific antipsychotic were associated with higher or lower response to antidepressant treatment. MDD was associated with Metabolic syndrome (31.4 v. 20.2%; P = 0.006) but not with increased C-reactive protein. CONCLUSIONS: Antidepressant administration is associated with lower depressive symptom level in patients with schizophrenia and MDD. Paranoid delusions and alcohol misuse disorder should be specifically explored and treated in cases of non-remission under treatment. MetS may play a role in MDD onset and/or maintenance in patients with schizophrenia.Declaration of interestNone.

Early and very early-onset schizophrenia compared with adult-onset schizophrenia: French FACE-SZ database.

OBJECTIVE: To compare the clinical symptomatology in patients with Early-Onset Schizophrenia (EOS, N = 176), especially the subgroup Very Early Onset Schizophrenia (VEOS) and Adult Onset Schizophrenia (AOS, N = 551). METHOD: In a large French multicentric sample, 727 stable schizophrenia patients, classified by age at onset of the disorder, were assessed using standardized and extensive clinical and neuropsychological batteries: AOS with onset ≥ 18 years and EOS with onset < 18 years (including 22 VEOS < 13 years). RESULTS: The importance of better diagnosing EOS group, and in particularly VEOS, appeared in a longer DUP Duration of Untreated Psychosis (respectively, 2.6 years ± 4.1 and 8.1 years ± 5.7 vs. 1.0 years ± 2.5), more severe symptomatology (PANSS Positive And Negative Syndrome Scale scores), and lower educational level than the AOS group. In addition, the VEOS subgroup had a more frequent childhood history of learning disabilities and lower prevalence of right-handedness quotient than the AOS. CONCLUSION: The study demonstrates the existence of an increased gradient of clinical severity from AOS to VEOS. In order to improve the prognosis of the early forms of schizophrenia and to reduce the DUP, clinicians need to pay attention to the prodromal manifestations of the disease.

Validation and refinement of the clinical staging model in a French cohort of outpatient with schizophrenia (FACE-SZ).

OBJECTIVE: Existing staging models have not been fully validated. Thus, after classifying patients with schizophrenia according to the staging model proposed by McGorry et al. (2010), we explored the validity of this staging model and its stability after one-year of follow-up. METHOD: Using unsupervised machine-learning algorithm, we classified 770 outpatients into 5 clinical stages, the highest being the most severe. Analyses of (co)variance were performed to compare each stage in regard to socio-demographics factors, clinical characteristics, co-morbidities, ongoing treatment and neuropsychological profiles. RESULTS: The precision of clinical staging can be improved by sub-dividing intermediate stages (II and III). Clinical validators of class IV include the presence of concomitant major depressive episode (42.6% in stage IV versus 3.4% in stage IIa), more severe cognitive profile, lower adherence to medication and prescription of >3 psychotropic medications. Follow-up at one-year showed good stability of each stage. CONCLUSION: Clinical staging in schizophrenia could be improved by adding clinical elements such as mood symptoms and cognition to severity, relapses and global functioning. In terms of therapeutic strategies, attention needs to be paid on the factors associated with the more stages of schizophrenia such as treatment of comorbid depression, reduction of the number of concomitant psychotropic medications, improvement of treatment adherence, and prescription of cognitive remediation.

Prevalence of and Risk Factors for Extrapyramidal Side Effects of Antipsychotics: Results From the National FACE-SZ Cohort.

BACKGROUND: Extrapyramidal side effects (EPS) have been identified as a complication of antipsychotic treatment. Previous meta-analyses have investigated EPS prevalence and risk factors in randomized clinical trials with highly selected patients, but studies in real-world schizophrenia are missing. OBJECTIVE: To examine the prevalence and clinical correlates associated with EPS in a nonselected national multicenter sample of stabilized patients with schizophrenia. METHODS: Between 2010 and 2016, patients suffering from schizophrenia (DSM-IV-TR criteria) were recruited through the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) network and data were collected during a comprehensive 1-day-long standardized evaluation. The Simpson-Angus Scale and the Abnormal Involuntary Movement Scale were used to assess drug-induced parkinsonism (DIP) and tardive dyskinesia, respectively. RESULTS: The overall prevalence of DIP and tardive dyskinesia was 13.2% and 8.3%, respectively, in this community-dwelling sample of 674 patients. DIP was associated with negative symptoms (Positive and Negative Syndrome Scale [PANSS] subscore) (adjusted odds ratio [aOR] = 1.102, P < .001), first-generation antipsychotic prescription (aOR = 2.038, P = .047), and anticholinergic drug administration (aOR = 2.103, P = .017) independently of sex, age, disorganization (PANSS disorganized factor), and antipsychotic polytherapy. Tardive dyskinesia was associated with PANSS disorganized factor (aOR = 1.103, P = .049) independently of sex, age, negative symptoms, excitation, first-generation antipsychotic prescription, and benzodiazepine and anticholinergic drug administration. CONCLUSIONS: Our results indicate the high prevalence of EPS in a nonselected community-dwelling clinically stable sample of outpatients with schizophrenia. In the monitoring of antipsychotic treatment, EPS should be systematically evaluated, especially when negative symptoms and disorganization or cognitive alteration are present. Monotherapy with a second-generation antipsychotic should be preferentially initiated for patients with these side effects.

Self-reported pain in patients with schizophrenia. Results from the national first-step FACE-SZ cohort.

INTRODUCTION: Little is known about perception of physical pain in schizophrenia (SZ). Some studies have suggested that patients with SZ may have an increased pain threshold, while others have suggested that patients with SZ may suffer from undetected and untreated high physical pain levels. The objectives of this study were (i) to investigate the prevalence of self-reported physical pain in stabilized SZ subjects, and (ii) to determine whether physical pain was associated with psychiatric characteristics and somatic comorbidities (iii) to determine whether antidepressants and benzodiazepine administration were associated with lower self-reported pain. METHOD: 468 community-dwelling stable SZ subjects (73% men, mean aged 32 years) were recruited in the Schizophrenia Expert Center national network. Patients with moderate to extreme pain, assessed with the EQ5D-5L questionnaire, were classified as belonging to the "pain group". RESULTS: 104 (22.2%) reported moderate to extreme pain levels. In multivariate analysis, pain has been associated with headache (OR = 2.63 [1.04-6.63], p = 0.04), higher anxiety (OR = 1.61 [1.18-2.21], p = 0.003), higher current depressive symptoms (OR = 1.09 [1.01-1.17], p = 0.03), history of childhood trauma (1.03 [1.01-1.06], p = 0.01) and older age (OR = 1.04 [1.01-1.07], p = 0.03), independently of current psychotic severity, sociodemographic variables, antipsychotic, antidepressant and benzodiazepine treatments. No association with addictive behaviors or illness characteristics has been found. CONCLUSION: The present findings suggest that community-dwelling SZ outpatients report a high rate of self-reported physical pain, associated with headache, depression and anxiety and history of childhood trauma. Physical pain should be systematically assessed and specifically treated, when needed, in patients with SZ.

Advanced paternal age is associated with earlier schizophrenia onset in offspring. Results from the national multicentric FACE-SZ cohort.

The association between advanced paternal age (APA) and increased risk of schizophrenia (SZ) is well established. The objectives of the present study were to further determine if SZ participants with APA (APA+), versus those without (APA-), had: (i) different illness characteristics; (ii) different responses to antipsychotic medication; and (iii) different cognitive characteristics. Participants were a non-selected representative multicentric sample of stabilized community-dwelling people diagnosed with SZ included in the FACE-SZ cohort. 389 participants (73% males, mean aged 32.7 years, mean illness duration 10.8 years) formed the study sample, with each comprehensively evaluated, clinically and neuropsychologically, over 2 days. 118 participants (30.3%) were defined as APA+ according to their father's age at birth (≥35 years). APA+ was associated with a wide range of cognitive dysfunctions in univariate analyses. In multivariate analyses, the only significant difference was the age at onset, with a mean 1.6 year earlier in APA+, compared to APA- (20.7 vs. 22.3 years; p=0.02). This difference is independent of sociodemographic characteristics and I.Q. No association with clinical symptomatology and treatment response was found. The present study supports the neomutation hypothesis and confirms APA as a relevant clinical variable to discriminate potential schizophrenia subtypes. Potential underlying pathophysiological mechanisms are discussed.

Clinical utility of the Multiple Errands Test in schizophrenia: A preliminary assessment.

Schizophrenia (SZ) is a chronic, severe disease, which results in misperception of reality, major social withdrawal, and cognitive disturbances. One type of cognitive disturbance, known as executive dysfunction, is widely considered as a primary determinant of functional outcome. However, classic neuropsychological measures of executive functioning (EF) poorly represent patients' functional outcome, and thus seem inappropriate for evaluating the real-world functional impact of diseases such as SZ. We hypothesized that the Multiple Errands Test (MET), an ecological assessment of executive function would show greater ability to measure everyday adaptive functioning SZ, compared to conventional EF assessment methods. 100 clinically stable SZ patients were administered the MET, Wisconsin Card Sorting Test - 64 and a paper version of MET. Correlation analyses were performed between each EF measure and functional outcome, as measured by the Social Autonomy Scale (SAS). After adjusting for age, education, IQ and illness duration, SAS was significantly predicted by MET global score. No other EF measure correlated with SAS. Results from this study suggest that MET offers a valuable prediction of daily life functional outcome in this large sample of SZ patients. Therefore, it could be used as a complementary measure to improve the identification of executive dysfunctions prior to psychosocial interventions.

WAIS-IV Seven-Subtest Short Form: Validity and Clinical Use in Schizophrenia.

OBJECTIVE: This study assesses the psychometric properties of Ward's seven-subtest short form (SF) for WAIS-IV in a sample of adults with schizophrenia (SZ) and schizoaffective disorder. METHOD: Seventy patients diagnosed with schizophrenia or schizoaffective disorder were administered the full version of the WAIS-IV. Four different versions of the Ward's SF were then calculated. The subtests used were: Similarities, Digit Span, Arithmetic, Information, Coding, Picture Completion, and Block Design (BD version) or Matrix Reasoning (MR version). Prorated and regression-based formulae were assessed for each version. RESULTS: The actual and estimated factorial indexes reflected the typical pattern observed in schizophrenia. The four SFs correlated significantly with their full-version counterparts, but the Perceptual Reasoning Index (PRI) correlated below the acceptance threshold for all four versions. The regression-derived estimates showed larger differences compared to the full form. The four forms revealed comparable but generally low clinical category agreement rates for factor indexes. All SFs showed an acceptable reliability, but they were not correlated with clinical outcomes. CONCLUSIONS: The WAIS-IV SF offers a good estimate of WAIS-IV intelligence quotient, which is consistent with previous results. Although the overall scores are comparable between the four versions, the prorated forms provided a better estimation of almost all indexes. MR can be used as an alternative for BD without substantially changing the psychometric properties of the SF. However, we recommend a cautious use of these abbreviated forms when it is necessary to estimate the factor index scores, especially PRI, and Processing Speed Index.

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.

A self administered executive functions ecological questionnaire (the behavior rating inventory of executive function - adult version) shows impaired scores in a sample of patients with schizophrenia.

Subjective measurements of cognition have seldom been used in schizophrenia. This is mainly due to the assumption that such measurements lack sensitivity in a disorder characterized by poor insight. We investigated the capacity of BRIEF-A (Behavior Rating Inventory of Executive Function - Adult Version: a self-administered, ecological questionnaire) to identify executive deficits in adults with schizophrenia. The global score and each domain-specific score was significantly lower in patients than in healthy controls. BRIEF-A could be a useful complement to objective measurements, providing a subjective assessment of everyday consequences of executive dysfunction in patients with schizophrenia.