A. Vignapiano

The Brief Negative Symptom Scale (BNSS): Independent validation in a large sample of Italian patients with schizophrenia.

BACKGROUND The Brief Negative Symptom Scale (BNSS) was developed to address the main limitations of the existing scales for the assessment of negative symptoms of schizophrenia. The initial validation of the scale by the group involved in its development demonstrated good convergent and discriminant validity, and a factor structure confirming the two domains of negative symptoms (reduced emotional/verbal expression and anhedonia/asociality/avolition). However, only relatively small samples of patients with schizophrenia were investigated. Further independent validation in large clinical samples might be instrumental to the broad diffusion of the scale in clinical research. METHODS The present study aimed to examine the BNSS inter-rater reliability, convergent/discriminant validity and factor structure in a large Italian sample of outpatients with schizophrenia. RESULTS Our results confirmed the excellent inter-rater reliability of the BNSS (the intraclass correlation coefficient ranged from 0.81 to 0.98 for individual items and was 0.98 for the total score). The convergent validity measures had r values from 0.62 to 0.77, while the divergent validity measures had r values from 0.20 to 0.28 in the main sample (n=912) and in a subsample without clinically significant levels of depression and extrapyramidal symptoms (n=496). The BNSS factor structure was supported in both groups. CONCLUSIONS The study confirms that the BNSS is a promising measure for quantifying negative symptoms of schizophrenia in large multicenter clinical studies.

The relationships of personal resources with symptom severity and psychosocial functioning in persons with schizophrenia: results from the Italian Network for Research on Psychoses study

The relationships of personal resources with symptom severity and psychosocial functioning have never been tested systematically in a large sample of people with schizophrenia. We applied structural equation models to a sample of 921 patients with schizophrenia collected in a nationwide Italian study, with the aim to identify, among a large set of personal resources, those that may have an association with symptom severity or psychosocial functioning. Several relevant demographic and clinical variables were considered concurrently. Poor service engagement and poor recovery style, as well as older age and younger age at onset, were related to greater symptom severity and poorer social functioning. Higher resilience and higher education were related to better social functioning only. Poor problem-focused coping and internalized stigma, as well as male gender and depression, were related to symptom severity only. The explored variables showed distinctive and partially independent associations with symptom severity and psychosocial functioning. A deeper understanding of these relationships may inform treatment decisions.

Interplay among psychopathologic variables, personal resources, context-related factors, and real-life functioning in individuals with schizophrenia a network analysis

Importance Enhanced understanding of factors associated with symptomatic and functional recovery is instrumental to designing personalized treatment plans for people with schizophrenia. To date, this is the first study using network analysis to investigate the associations among cognitive, psychopathologic, and psychosocial variables in a large sample of community-dwelling individuals with schizophrenia. Objective To assess the interplay among psychopathologic variables, cognitive dysfunctions, functional capacity, personal resources, perceived stigma, and real-life functioning in individuals with schizophrenia, using a data-driven approach. Design, Setting, and Participants This multicenter, cross-sectional study involved 26 university psychiatric clinics and/or mental health departments. A total of 921 community-dwelling individuals with a DSM-IV diagnosis of schizophrenia who were stabilized on antipsychotic treatment were recruited from those consecutively presenting to the outpatient units of the sites between March 1, 2012, and September 30, 2013. Statistical analysis was conducted between July 1 and September 30, 2017. Main Outcomes and Measures Measures covered psychopathologic variables, neurocognition, social cognition, functional capacity, real-life functioning, resilience, perceived stigma, incentives, and service engagement. Results Of 740 patients (221 women and 519 men; mean [SD] age, 40.0 [10.9] years) with complete data on the 27 study measures, 163 (22.0%) were remitted (with a score of mild or better on 8 core symptoms). The network analysis showed that functional capacity and everyday life skills were the most central and highly interconnected nodes in the network. Psychopathologic variables split in 2 domains, with positive symptoms being one of the most peripheral and least connected nodes. Functional capacity bridged cognition with everyday life skills; the everyday life skills node was connected to disorganization and expressive deficits. Interpersonal relationships and work skills were connected to avolition; the interpersonal relationships node was also linked to social competence, and the work skills node was linked to social incentives and engagement with mental health services. A case-dropping bootstrap procedure showed centrality indices correlations of 0.75 or greater between the original and randomly defined samples up to 481 of 740 case-dropping (65.0%). No difference in the network structure was found between men and women. Conclusions and Relevance The high centrality of functional capacity and everyday life skills in the network suggests that improving the ability to perform tasks relevant to everyday life is critical for any therapeutic intervention in schizophrenia. The pattern of network node connections supports the implementation of personalized interventions.

Physiological Correlates of Positive Symptoms in Schizophrenia

Patients with schizophrenia have been hypothesized to have a functional impairment in filtering irrelevant sensory information, which may result in positive symptoms such as hallucinations or delusions. Many evidences suggest that abnormalities in the event-related brain potentials (ERPs), resting state electroencephalography (EEG) and synchronized oscillatory activity of neurons may reflect core pathophysiological mechanisms of schizophrenia. Abnormalities in amplitude and latency of the ERPs reflecting aberrations in gating and difficulties in the detection of changes in auditory stimuli, as well as defects in stimuli evaluation and integration of information are common in patients with schizophrenia. This chapter highlights the findings of electrophysiological studies in schizophrenia dealing with early sensory perception and attention, automatic sensory detection of stimuli changes and cognitive evaluation and integration of information, relevant to the pathophysiological mechanisms underpinning hallucinations and delusions. Results of electrophysiological studies investigating the neural correlates of positive symptoms suggest aberrant intrinsic organization of functional brain networks.

Avolition-Apathy and White Matter Connectivity in Schizophrenia: Reduced Fractional Anisotropy Between Amygdala and Insular Cortex

The avolition/apathy domain of negative symptoms includes motivation- and pleasure-related impairments. In people with schizophrenia, structural and functional abnormalities were reported in key regions within the motivational reward system, including ventral-tegmental area (VTA), striatum (especially at the level of the nucleus accumbens, NAcc), orbitofrontal cortex (OFC), as well as amygdala (Amy) and insular cortex (IC). However, the association of the reported abnormalities with avoliton-apathy is still controversial. In the present study, we investigated white matter connectivity patterns within these regions, using a probabilistic analysis of diffusion tensor imaging (DTI) data, in male subjects with schizophrenia. Thirty-five male subjects with schizophrenia (SCZ) and 17 male healthy controls (HC) matched for age, underwent DTI. SCZ were evaluated using the Schedule for Deficit Syndrome (SDS), the Positive and Negative Syndrome Scale (PANSS), and the MATRICS Consensus Cognitive Battery (MCCB). Probabilistic tractography was applied to investigate pathways connecting the Amy and the NAcc with the OFC and IC. Reduced fractional anisotropy (FA) was observed in left Amy–ventral anterior IC connections, in SCZ compared with controls. This abnormality was negatively correlated with avolition/apathy but not with expressive deficit scores. SCZ showed also a reduced connectivity index between right NAcc and medial OFC, as compared with controls. Finally, the left NAcc-dorsal anterior IC connectivity index was negatively correlated with working memory scores. Our results indicate that only the avolition/apathy domain of negative symptoms is related to abnormal connectivity in the motivation-related circuits. The findings also demonstrate that distinct alterations underlie cognitive impairment and avolition/apathy.

Personal resources and depression in schizophrenia: The role of self-esteem, resilience and internalized stigma

Depression in schizophrenia represents a challenge from a diagnostic, psychopathological and therapeutic perspective. The objective of this study is to test the hypothesis that resilience and self-stigma affect depression severity and to evaluate the strength of their relations in 921 patients with schizophrenia. A structural equation model was tested where depression is hypothesized as affected by resilience, internalized stigma, gender and negative symptoms, with the latter two variables used as exogenous covariates and the former two as mediators. The analysis reveals that low resilience, high negative symptoms, female gender were directly associated with depression severity, and internalized stigma acted only as a mediator between avolition and resilience, with similar magnitude. The cross-sectional study design and the variable selection limit the generalizability of the study results. The model supports a complex interaction between personal resources and negative symptoms in predicting depression in schizophrenia. The clinical implication of these findings is that personal resources could be a significant target of psychosocial treatments.

P300 Correlates of Cognitive Dysfunctions in Schizophrenia

Introduction P300 is an event-related potential (ERP) thought to reflect attention, working memory and context integration and has been shown to be consistently reduced in patients with Schizophrenia. Despite a possible relation between P300 components and cognitive deficits in Schizophrenia has been hypothesized, few studies addressed this hypothesis. Objectives In the context of a multicenter study of the Italian Network for Research on Psychoses, our study focused on the investigation of auditory P300 component in relation to clinical and cognitive domains in patients with Schizophrenia. Methods ERPs were recorded in 64 chronic, stabilized patients with Schizophrenia during a standard oddball task. N1 and P3b latency and amplitude were assessed at Fz and Pz, respectively. State of art instruments was used for clinical assessment. Cognitive indices (from the seven cognitive domains of the Measurement and Treatment of Cognition in Schizophrenia, MATRICS) were expressed as Z-scores from an Italian normative sample. Results Correlation analysis revealed associations of P3b latency with age, education, PANSS-DIS, processing speed, working memory, St. Hans parkinsonism subscale. In a multiple linear regression model, processing speed was an independent significant predictor of P3b latency. Conclusion For the first time, a strong relation between P3b latency and processing speed impairment was shown in Schizophrenia. Processing speed is considered a central factor in the relation between cognitive deficits and functional outcome in chronic schizophrenia. The association with P3b latency might shed lights in the neural basis of this complex construct.

Add-on oral olanzapine worsens hallucinations in schizoaffective disorder

Anecdotal evidence tends to favour olanzapine in the treatment of hallucinations in patients with schizophrenia spectrum disorders; however, no conclusive evidence is available on this topic. We report here a clinical case in which a 46-year-old man, suffering from a schizoaffective disorder (depressed type), underwent olanzapine treatment (20 mg/day). After inducing an initial amelioration, the patient had a re-exacerbation of auditory hallucinations and a clinical and psychosocial worsening, which subsided after olanzapine discontinuation. Olanzapine may induce a worsening of hallucinations in a psychotic disorder with substantial affective component and therefore its use should be carefully evaluated in such cases.

P03-98 - Effects of antipsychotics on cognitive functions: an ERP study in healthy controls

Introduction Clinical studies on cognitive effects of second generation antipsychotics produced disappointing findings probably due to the heterogeneity of the clinical populations under investigation, as well as to poor sensitivity of neurocognitive indices. Event-Related Potentials (ERPs) provide a functional measure of electrical brain activity time-locked to discrete stages of information processing. They have been widely used as putative biological markers of cognitive abnormalities in schizophrenia and represent useful indices in the investigation of the cognitive effects of psychotropic drugs. Objectives The present study investigated the effect of risperidone, haloperidol and placebo on N1 and P3 in male healthy subjects. Methods ERPs were recorded during a three-tone oddball task in which target, standard and rare-nontarget tones were randomly presented. Subjects had to press a button when hearing a target tone. Amplitude and topography of the ERP component maps at peak latencies were compared across conditions. If a significant drug effect was obtained, changes in the cortical sources of the corresponding ERP component were analyzed using Low-Resolution Electromagnetic Tomography (LORETA). Results The amplitude of N1 for attended stimuli and of P3 for rare-nontargets (P3a) was significantly increased only by risperidone. No significant change was observed in overall topographic features and in LORETA cortical sources of the same components. No significant drug effect was demonstrated for the latency of all the investigated components and for P3b amplitude. Conclusions Our findings suggest that risperidone has a favorable effect on early attention processes and automatic attention allocation.

Neurobiology of Schizophrenia: Electrophysiological Indices

The objective of the WPA section on Psychoneurobiology is the promotion of the integration of findings from research fields such as neurophysiology, psychology, neuropsychology and psychiatry. This chapter focuses on the importance of electroencephalographic (EEG) studies for the section’s objectives and especially for (a) the study of functional brain abnormalities related to liability to psychosis and schizophrenia pathophysiology and (b) characterization of schizophrenia psychopathological dimensions. The introduction will highlight the importance of EEG investigations in psychiatry, outlining a model of brain function, based on the notion of state-dependent information processing, and providing examples relevant to schizophrenia research. The second paragraph will summarize the current state of knowledge about resting state EEG connectivity in subjects with schizophrenia (SCZ) and draw some tentative conclusions about the possible links to the range of cognitive and behavioural abnormalities observed in these patients. The third paragraph will illustrate findings from event-related potential (ERP) studies of subjects at risk for psychosis who later develop schizophrenia-spectrum disorders. Some of the ERP parameters are proposed as biomarkers of the transition to psychosis and, if further validated, can be used to identify subjects for early interventions. The final paragraph of the chapter will summarize findings relevant to the characterization of the psychopathological dimensions of schizophrenia.