Immuno-metabolic profile of patients with psychotic disorders and metabolic syndrome. Results from the FACE-SZ cohort.

Background: Metabolic syndrome (MetS) is a highly prevalent and harmful medical disorder often comorbid with psychosis where it can contribute to cardiovascular complications. As immune dysfunction is a key shared component of both MetS and schizophrenia (SZ), this study investigated the relationship between immune alterations and MetS in patients with SZ, whilst controlling the impact of confounding clinical characteristics including psychiatric symptoms and comorbidities, history of childhood maltreatment and psychotropic treatments. Method: A total of 310 patients meeting DSM-IV criteria for SZ or schizoaffective disorders (SZA), with or without MetS, were systematically assessed and included in the FondaMental Advanced Centers of Expertise for Schizophrenia (FACE-SZ) cohort. Detailed clinical characteristics of patients, including psychotic symptomatology, psychiatric comorbidities and history of childhood maltreatment were recorded and the serum levels of 18 cytokines were measured. A penalized regression method was performed to analyze associations between inflammation and MetS, whilst controlling for confounding factors. Results: Of the total sample, 25% of patients had MetS. Eight cytokines were above the lower limit of detection (LLOD) in more than 90% of the samples and retained in downstream analysis. Using a conservative Variable Inclusion Probability (VIP) of 75%, we found that elevated levels of interleukin (IL)-6, IL-7, IL-12/23 p40 and IL-16 and lower levels of tumor necrosis factor (TNF)-α were associated with MetS. As for clinical variables, age, sex, body mass index (BMI), diagnosis of SZ (not SZA), age at the first episode of psychosis (FEP), alcohol abuse, current tobacco smoking, and treatment with antidepressants and anxiolytics were all associated with MetS. Conclusion: We have identified five cytokines associated with MetS in SZ suggesting that patients with psychotic disorders and MetS are characterized by a specific "immuno-metabolic" profile. This may help to design tailored treatments for this subgroup of patients with both psychotic disorders and MetS, taking one more step towards precision medicine in psychiatry.

Neurological Soft Signs and Post-Traumatic Stress Disorder: A Biomarker of Severity?

BACKGROUND: The psychophysiological changes for individual suffering from chronic post-traumatic stress disorder (PTSD) raise to the questions of how facilitate recovery and return to work. Negative alterations in neuro-cognition remain a complaint for patients and participate to long-term functional impairments. Neurological soft signs (NSSs) appear as a candidate for better understanding these complaints. They have been reported in several mental disorders. They are found in several behavioral and/or neurocognitive disorders and are taken into account by psychiatric rehabilitation programs to support recovery. As few studies evaluate NSSs in PTSD, our exploratory study aims to assess NSSs in chronic PTSD and their relationships with PTSD severity. METHOD: Twenty-two patients with a clinical diagnosis of chronic PTSD were evaluated in terms of PTSD severity (post-traumatic checklist scale, PCL5), NSSs (NSSs psychomotor skills scale, PASS), and well-being upon arrival to the hospital and compared with 15 healthy subjects. Statistical non-parametric analyses assessed the relationships between these variables. RESULTS: PTSD subjects exhibited higher NSSs compared with healthy subjects. NSSs were positively associated with PTSD severity, with negative alterations in cognition and mood, and with impairment in well-being. They were higher in women compared with men. No impact of age was found. Three groups were identified based on the severity of the PTSD. Severe PTSD exhibited NSSs characterized by motor integration alterations. CONCLUSIONS: This pilot study suggests that NSSs might be a biomarker of PTSD severity. This proof of concept highlights the need for further research for better evaluating the clinical neuro-functional impairment. This will be helping for defining neurological remediation for promoting PTSD recovery.

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.

Modeling the Longitudinal Effects of Insight on Depression, Quality of Life and Suicidality in Schizophrenia Spectrum Disorders: Results from the FACE-SZ Cohort.

BACKGROUND: Up to half of the patients with schizophrenia attempt suicide during their lifetime. Better insight is associated with better functioning but also with increased suicidality. The direction of the relationship between insight and suicidality is not clear, hence we aimed to provide new elements using structural equation modeling. METHODS: Insight, quality of life (QoL), depression, and suicidality were measured at baseline and at 12 months in individuals with schizophrenia spectrum disorders. The relationships between these variables were investigated by latent difference score models, controlling for chlorpromazine doses, positive and negative symptoms, and general psychopathology. RESULTS: 738 patients were included, and 370 completed the study. Baseline levels of insight predicted changes in suicidality, whereas baseline levels of suicidality did not predict changes in insight, suggesting that better insight underlies suicidality and predicts its worsening. Our results suggest this temporal sequence: better insight → worse QoL → increased depression → increased suicidality, while insight also affects the three variables in parallel. CONCLUSION: Better insight predicts a worsening of QoL, depression and suicidality. These findings contribute to our global understanding of the longitudinal influence of insight on suicidality. We advocate that insight-targeted interventions should not be proposed without the monitoring of depression and suicide prevention.

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.

Metabolic Syndrome and Illness Severity Predict Relapse at 1-Year Follow-Up in Schizophrenia: The FACE-SZ Cohort.

OBJECTIVE: Predicting relapse is a major challenge in schizophrenia from a clinical and medico-economic point of view. During recent decades, major psychiatric disorders have been found to be extensively associated with metabolic disorders, even before the illness onset, with a prevalence estimated to be 35% in this population. However, no study to date has, to our knowledge, explored the potential impact of metabolic syndrome (MetS) on relapse. METHODS: From 2010 to 2016, 185 patients (mean age = 32 years) with a DSM-IV-TR diagnosis of schizophrenia were included in the FondaMental Academic Centers of Expertise for Schizophrenia (FACE-SZ) cohort and followed up for 1 year. Multivariable logistic regression was performed to estimate the adjusted odds ratio for relapse. RESULTS: Thirty-seven percent of stabilized outpatients with schizophrenia (mean illness duration = 11 years) experienced a relapse at least once during the 1 year of follow-up. MetS strongly predicted relapse at 1 year, independently of illness severity, insight into illness, and treatment characteristics (including medication compliance). Patients with MetS at baseline had a 3 times higher risk (95% CI, 1.1-8.4) of experiencing a new episode of psychosis during the 12 months of follow-up. CONCLUSIONS: Further studies should determine if reducing or preventing MetS could help to protect subjects with schizophrenia from relapse.

Toward a transdiagnostic tool to evaluate depressive symptoms across mental disorders: Validation of the Calgary depression rating scale in patients with major depressive disorder.

The severity of depressive symptoms across two discrete mental disorders should be evaluated with the same psychometrically validated tools. In patients with schizophrenia the Calgary Depression Rating Scale (CDSS) is recommended for evaluating depressive symptoms. The aim of this study was to validate the CDSS in patients with major depressive disorder. The CDSS exhibit satisfactory psychometric properties for evaluating depressive symptoms in major depressive disorder. Clinicians and researchers now have a validated scale at their disposal to evaluate depressive symptoms in various mental disorders using a transdiagnostic approach.

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.

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.

Nicotine dependence is associated with depression and childhood trauma in smokers with schizophrenia: results from the FACE-SZ dataset.

In a perspective of personalized care for smoking cessation, a better clinical characterization of smokers with schizophrenia (SZ) is needed. The objective of this study was to determine the clinical characteristics of SZ smokers with severe nicotine (NIC) dependence. 240 stabilized community-dwelling SZ smokers (mean age = 31.9 years, 80.4% male gender) were consecutively included in the network of the FondaMental Expert Centers for Schizophrenia and assessed with validated scales. Severe NIC dependence was defined by a Fagerstrom questionnaire score ≥ 7. Depression was defined by a Calgary score ≥ 6. Childhood trauma was self-reported by the Childhood Trauma Questionnaire score (CTQ). Ongoing psychotropic treatment was recorded. Severe NIC dependence was identified in 83 subjects (34.6%), depression in 60 (26.3%). 44 (22.3%) subjects were treated by antidepressants. In a multivariate model, severe NIC dependence remained associated with depression (OR = 3.2, p = 0.006), male gender (OR = 4.5, p = 0.009) and more slightly with childhood trauma (OR = 1.03, p = 0.044), independently of socio-demographic characteristics, psychotic symptoms severity, psychotropic treatments and alcohol disorder. NIC dependence was independently and strongly associated with, respectively, depression and male gender in schizophrenia, and only slightly with history of childhood trauma. Based on these results, the care of both nicotine dependence and depression should be evaluated for an effective smoking cessation intervention in schizophrenia.

Validation study of the Medication Adherence Rating Scale. Results from the FACE-SZ national dataset.

OBJECTIVE: The Medication Adherence Rating Scale (MARS) is one of the most widely used measurements of adherence in schizophrenia (SZ). However, the data available regarding its psychometric properties are scarce. The aim of this study was to provide new data regarding the psychometric properties of the MARS in a multicenter community-dwelling sample of SZ patients. METHODS: This study was conducted in the French National network of the 10 FondaMental Expert Centers for SZ. The MARS was tested for construct validity, reliability, external validity and acceptability. In addition, data pertaining to sociodemographic information, clinical characteristics using the Positive and Negative Syndrome Scale (PANSS), the Scale to Assess Unawareness in Mental Disorder (SUMD), the Calgary Depression Scale for Schizophrenia (CDRS) and therapeutic adherence using the Brief Adherence Rating Scale (BARS) were collected. RESULTS: Three hundred and nineteen patients were included. The 3-factor structure of the MARS was confirmed using confirmatory factor analysis: RMSEA=0.05, CFI=0.95, and WRMR=0.88. The unidimensionality of each factor was supported by the satisfactory INFIT statistics. Item internal consistencies were all higher than 0.15 and the Kuder-Richardson were close to 0.6, except for factor 2, which was close to 0.5. Significant associations with BARS, PANSS, CDRS showed satisfactory external validity. The acceptability was excellent as all patients complete the MARS, without missing values. CONCLUSION: The MARS is a short self-administered instrument with acceptable psychometric properties that yields important information about adherence to pharmacological treatment. Some improvements might be considered to enhance its validity and reliability.

Determination of Adherence Profiles in Schizophrenia Using Self-Reported Adherence: Results From the FACE-SZ Dataset.

OBJECTIVE: Medication nonadherence is one of the most important, and potentially modifiable, prognostic factors in the outcome of patients with schizophrenia. The aim of this article is to propose a new classification of adherence profiles according to the Medication Adherence Rating Scale (MARS) in a large community-dwelling sample of French patients with schizophrenia to provide a new tool to help clinicians in daily practice. METHODS: 319 community-dwelling patients from a national network of 10 Schizophrenia Expert Centers were interviewed between January 2009 and January 2014. Assessments were conducted with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Disorders. A cluster analysis was performed to explore clinical variables associated with poor adherence. RESULTS: Two distinct groups of patients were identified relative to their main adherence style. Items about medications' subjective negative effects constituted the greatest discriminating factor between the 2 clusters. Patients with poor adherence (n = 117) were significantly younger (adjusted OR [aOR] = 1.036; 95% CI, 1.004-1.069) and had higher levels of current depression (aOR = 0.894; 95% CI, 0.829-0.964) and lower insight (aOR = 0.820; 95% CI, 0.693-0.970). CONCLUSIONS: The MARS provides a useful tool for clinicians and can also aid in the evaluation of adherence styles and their determinants in patients with schizophrenia. The element providing the greatest discriminative power between the 2 clusters was a subjective negative attitude toward medication. The findings also suggest that depression is more frequent in schizophrenia patients with poor adherence and that improving insight into illness might be suggested as a first-line intervention to improve adherence in 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.

Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1-Year Longitudinal Study.

Apathy, described as impaired motivation and goal-directed behavior, is a common yet often overlooked multidimensional psychopathological state in schizophrenia. Its underlying cognitive processes remain largely unexplored. Data was drawn from a longitudinal hospital study of patients with a DSM-IV diagnosis of schizophrenia; 137 (82.5%) participated at the 1-month follow-up and 81 (59.1%) at the 1-year follow-up. Apathy was assessed with the Lille Apathy Rating Scale, validated in French and in schizophrenia. Severe apathy, overall (total score > -13) and on 4 previously identified distinct dimensions, was considered. Episodic verbal learning was assessed with the California Verbal Learning Test, executive functioning with the Trail Making Test, the Six Element Test and the Stop Signal Paradigm and working memory with the Letter-Number Sequencing Test. After controlling for confounding variables, only episodic verbal learning was associated with severe overall apathy in the cross-sectional study. At 1 year, working memory was associated with an increased risk of severe overall apathy, adjusting for baseline apathy. Using a dimensional approach to apathy, specific types of cognition were found to be associated with specific dimensions of apathy. Our findings confirm the need for a multidimensional approach of negative symptoms in schizophrenia. Moreover, cognitive functioning could be a risk factor for developing severe apathy. Cognitive remediation may thus be a useful non-pharmacological intervention for treating apathy in schizophrenia patients.

Elevated C-reactive protein is associated with sensory gating deficit in schizophrenia.

Sensory and cognitive impairments and inflammatory processes are contributing factors to the pathogenesis of schizophrenia. A previous study found that an elevated CRP level (≥5mg/L) was associated with higher cognitive impairments in schizophrenia. We aimed to investigate the association between an elevated CRP level and sensory impairments defined by a sensory gating deficit (abnormal P50 suppression) in 55 outpatients. Fifteen patients (27.3%) had an elevated CRP level that was associated with higher rate of sensory gating deficit (60% vs. 12.5%, p<0.001). This is the first study suggesting a relationship between sensory gating deficit and inflammatory processes in schizophrenia.

Association of metabolic syndrome with sensory gating deficits in patients with chronic schizophrenia.

Metabolic syndrome is more prevalent in schizophrenia than in the general population and is associated with an increased rate of morbidity. It has been associated with cognitive impairments in schizophrenia, which are a core deficit in patients with chronic schizophrenia. Sensory gating deficit is also a core deficit in schizophrenia. The principal objective of this study was to investigate the relationship between sensory gating deficit and metabolic syndrome in patients with schizophrenia, after adjusting for key confounding factors. We hypothesized that patients with metabolic syndrome exhibit a higher rate of sensory gating deficit compared to those without metabolic syndrome. This study investigated sensory gating with the auditory event-related potential method by measuring P50 amplitude changes in a double click conditioning-testing procedure in 51 patients with schizophrenia. Patients with metabolic syndrome (n = 14) had a higher rate of sensory gating deficit (P50 suppression <50%) (p < 0.001) compared to those without metabolic syndrome (n = 37). This result remained significant (B = 2.94, Wald = 8.32, p = 0.004) after taking into account 5 potential confounding factors (age, gender, duration of disorder, Fagerström test, presence of clozapine or olanzapine). In patients without metabolic syndrome, sensory gating deficit was linked to a poorer attentional performance (rho = -0.371, p = 0.05). In patients with metabolic syndrome, sensory gating deficit was linked to poorer memory performance (rho = -0.635, p = 0.02). These findings suggest that metabolic syndrome may be linked to sensory gating deficit in patients with schizophrenia and that the relationship between neurocognitive function and sensory gating deficit could be affected by the metabolic status of the patients. Further studies are needed to address the causal relationship between sensory gating deficit related to schizophrenia, cognitive impairments and metabolic syndrome.

Effects of clozapine on perceptual abnormalities and sensory gating: a preliminary cross-sectional study in schizophrenia.

The aim of the present study was to investigate the effect of second-generation antipsychotics (clozapine or another second-generation antipsychotic) on perceptual abnormalities related to sensory gating deficit. Although clozapine is known to improve sensory gating assessed neurophysiologically, we hypothesized that patients with schizophrenia treated with clozapine would report less perceptual abnormalities related to sensory gating deficit than patients treated with other second-generation antipsychotics do. Forty patients with a diagnosis of schizophrenia were investigated (10 patients treated with clozapine and 30 patients treated with another second-generation antipsychotic drug). Perceptual abnormalities were assessed with the Sensory Gating Inventory. Sensory gating was assessed through electroencephalogram with the auditory event-related potential method by measuring P50 amplitude changes in a dual click conditioning-testing procedure. Patients treated with clozapine present normal sensory gating and report less perceptual abnormalities related to sensory gating than patients treated with other second-generation antipsychotics do. Although the cross-sectional design of this study is limited because causal inferences cannot be clearly concluded, the present study suggests clinical and neurophysiological advantages of clozapine compared with other second-generation antipsychotics and provides a basis for future investigations on the effect of this treatment on perceptual abnormalities related to sensory gating deficit in patients with schizophrenia.

Perceptually or conceptually driven recognition: on the specificities of the memory deficit in schizophrenia.

This study explored the effects of exemplar changes on visual object recognition in patients with schizophrenia and paired control subjects. The experimental design was derived from the process-dissociation procedure (PDP: Jacoby, 1991). The objects presented at test could be the same exemplar as at study (physically identical picture), a different exemplar of the same object category, or a new, non-studied object. In the inclusion task, participants had to generalize their recognition to the conceptual level by accepting both different and identical exemplars as old. In the exclusion task, on the other hand, they had to accept only the same exemplars of the studied objects as old. Overall, performance was better on the inclusion task than on the exclusion task; schizophrenia patients performed worse than controls on the inclusion task but not the exclusion task, misrecognizing different exemplars more often than healthy controls. The present findings reveal that both recollection and familiarity are impaired in patients with schizophrenia, who present a relational, conceptually driven memory deficit. This deficit does not allow them to recognize an object as a member of a specific category independently of perceptual variations. This retrieval mode influences their subjective awareness of items׳ familiarity, and should be considered as a target for remediation.