Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program

The association between insight and depressive symptoms in schizophrenia: Undirected and Bayesian network analyses

Background. Greater levels of insight may be linked with depressive symptoms among patients with schizophrenia, however, it would be useful to characterize this association at symptom-level, in order to inform research on interventions. Methods. Data on depressive symptoms (Calgary Depression Scale for Schizophrenia) and insight (G12 item from the Positive and Negative Syndrome Scale) were obtained from 921 community-dwelling, clinically-stable individuals with a DSM-IV diagnosis of schizophrenia, recruited in a nationwide multicenter study. Network analysis was used to explore the most relevant connections between insight and depressive symptoms, including potential confounders in the model (neurocognitive and social-cognitive functioning, positive, negative and disorganization symptoms, extrapyramidal symptoms, hostility, internalized stigma, and perceived discrimination). Bayesian network analysis was used to estimate a directed acyclic graph (DAG) while investigating the most likely direction of the putative causal association between insight and depression. Results. After adjusting for confounders, better levels of insight were associated with greater self-depreciation, pathological guilt, morning depression and suicidal ideation. No difference in global network structure was detected for socioeconomic status, service engagement or illness severity. The DAG confirmed the presence of an association between greater insight and self-depreciation, suggesting the more probable causal direction was from insight to depressive symptoms. Conclusions. In schizophrenia, better levels of insight may cause self-depreciation and, possibly, other depressive symptoms. Person-centered and narrative psychotherapeutic approaches may be particularly fit to improve patient insight without dampening self-esteem

Social cognition in people with schizophrenia: A cluster-analytic approach

Background The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. Method A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. Results We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. Conclusions If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person

Mismatch Negativity and P3a Impairment through Different Phases of Schizophrenia and Their Association with Real-Life Functioning

Impairment in functioning since the onset of psychosis and further deterioration over time is a key aspect of subjects with schizophrenia (SCZ). Mismatch negativity (MMN) and P3a, indices of early attention processing that are often impaired in schizophrenia, might represent optimal electrophysiological candidate biomarkers of illness progression and poor outcome. However, contrasting findings are reported about the relationships between MMN-P3a and functioning. The study aimed to investigate in SCZ the influence of illness duration on MMN-P3a and the relationship of MMN-P3a with functioning. Pitch (p) and duration (d) MMN-P3a were investigated in 117 SCZ and 61 healthy controls (HCs). SCZ were divided into four illness duration groups: ≤ 5, 6 to 13, 14 to 18, and 19 to 32 years. p-MMN and d-MMN amplitude was reduced in SCZ compared to HCs, independently from illness duration, psychopathology, and neurocognitive deficits. p-MMN reduction was associated with lower “Work skills”. The p-P3a amplitude was reduced in the SCZ group with longest illness duration compared to HCs. No relationship between P3a and functioning was found. Our results suggested that MMN amplitude reduction might represent a biomarker of poor functioning in SCZ

Neurophysiological correlates of Avolition-apathy in schizophrenia: A resting-EEG microstates study

Background: The “Avolition-apathy” domain of the negative symptoms was found to include different symptoms by factor analytic studies on ratings derived by different scales. In particular, the relationship of anhedonia with this domain is controversial. Recently introduced negative symptom rating scales provide a better assessment of anhedonia, allowing the distinction of anticipatory and consummatory aspects, which might be related to different psychopathological dimensions. The study of associations with external validators, such as electrophysiological, brain imaging or cognitive indices, might shed further light on the status of anhedonia within the Avolition-apathy domain. Objectives: We used brain electrical microstates (MSs), which represent subsecond periods of quasi-stable scalp electrical field, associated with resting-state neural networks (and thus with global patterns of functional connectivity), to test whether the component symptoms of Avolition-apathy share the same correlates. Method: We analyzed multichannel resting EEGs in 142 individuals with schizophrenia (SCZ) and in 64 healthy controls (HC), recruited within the add-on EEG study of the Italian Network for Research on Psychoses. Relative time contribution, duration and occurrence of four MS classes (MS-A/-B/-C/−D) were calculated. Group differences on MS parameters (contribution and duration) and their associations with negative symptom domains (assessed using the Brief Negative Symptoms Scale) were investigated. Results: SCZ, in comparison to HC, showed increased contribution and duration of MS-C. The contribution of MS-A positively correlated with Avolition-apathy, but not with Expressive deficit. Within the Avolition-apathy domain, anticipatory anhedonia, avolition and asociality, but not consummatory anhedonia, showed the same correlations with MS-A contribution. Conclusion: Our findings support the existence of distinct electrophysiological correlates of Avolition-apathy with respect to Expressive deficit, and lend support to the hypothesis that only the anticipatory component of anhedonia shares the same pathophysiological underpinnings of the Avolition-apathy domain. Keywords: Schizophrenia, Avolition-apathy, Anhedonia, Resting-EEG, Brain electrical microstate

Investigating the relationships of P3b with negative symptoms and neurocognition in subjects with chronic schizophrenia

Neurocognitive deficits and negative symptoms (NS) have a pivotal role in subjects with schizophrenia (SCZ) due to their impact on patients' functioning in everyday life and their influence on goal-directed behavior and decision-making. P3b is considered an optimal electrophysiological candidate biomarker of neurocognitive impairment for its association with the allocation of attentional resources to task-relevant stimuli, an important factor for efficient decision-making, as well as for motivation-related processes. Furthermore, associations between P3b deficits and NS have been reported. The current research aims to fill the lack of studies investigating, in the same subjects, the associations of P3b with multiple cognitive domains and the expressive and motivation-related domains of NS, evaluated with state-of-the-art instruments. One hundred and fourteen SCZ and 63 healthy controls (HCs) were included in the study. P3b amplitude was significantly reduced and P3b latency prolonged in SCZ as compared to HCs. In SCZ, a positive correlation was found between P3b latency and age and between P3b amplitude and the Attention-vigilance domain, while no significant correlations were found between P3b and the two NS domains. Our results indicate that the effortful allocation of attention to task-relevant stimuli, an important component of decision-making, is compromised in SCZ, independently of motivation deficits or other NS

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses

Background: A general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia.Methods: We used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia.Results: We found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC).Conclusions: Overall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia. (C) 2018 Elsevier B.V. All rights reserved

Genome-wide association study detected novel susceptibility genes for social cognition impairment in people with schizophrenia

Objectives People with schizophrenia (SCZ) present serious and generalised deficits in social cognition (SC), which affect negatively patients' functioning and treatment outcomes. The genetic background of SC has been investigated in disorders other than SCZ providing weak and sparse results. Thus, our aim was to explore possible genetic correlates of SC dysfunctions in SCZ patients with a genome-wide study (GWAS) approach. Methods We performed a GWAS meta-analysis of data coming from two cohorts made of 242 and 160 SCZ patients, respectively. SC was assessed with different tools in order to cover its different domains. Results We found GWAS significant association between the TMEM74 gene and the patients' ability in social inference as assessed by The Awareness of Social Inference Test; this association was confirmed by both SNP-based analysis (lead SNP rs3019332 p-value = 5.24 x 10(-9)) and gene-based analysis (p-value = 1.09 x 10(-7)). Moreover, suggestive associations of other genes with different dimensions of SC were also found. Conclusions Our study shows for the first time GWAS significant or suggestive associations of some gene variants with SC domains in people with SCZ. These findings should stimulate further studies to characterise the genetic underpinning of SC dysfunctions in SCZ