Magnetic Resonance Imaging (MRI) measures are promising outcome markers for schizophrenia, since regional frontal and temporal grey matter volumes reductions, and enlargement of the ventricles, have ...been associated with outcome in this disorder. However, a number of methodological issues have limited the potential clinical utility of these findings. This article reviewed studies that examined brain structure at illness onset as a predictor of outcome, discusses the limitations of the findings, and highlights the challenges that would need to be addressed if structural data are to inform the management of an individual patient.
Using a set of a priori criteria, we systematically searched Medline and EMBASE databases for articles evaluating brain structure at the time of the first psychotic episode and assessed response to treatment, symptomatic outcome, or functional outcome at any point in the first 12 months of illness.
The 11 studies identified suggest that alterations in medial temporal and prefrontal cortical areas, and in the networks that connect them with subcortical structures, are promising neuroanatomical markers of poor symptomatic and functional outcomes.
Neuroimaging data, possibly in combination with other biomarkers of disease, could help stratifying patients with psychoses to generate patient clusters clinically meaningful, and useful to detect true therapeutic effects in clinical trials. Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE), a large multicenter study funded by the FP7 European Commission, could generate these much-needed findings.
The current study aimed to investigate alterations of event-related potentials (ERPs) microstate during reward anticipation in subjects with schizophrenia (SCZ), and their association with hedonic ...experience and negative symptoms. EEG data were recorded in thirty SCZ and twenty-three healthy controls (HC) during the monetary incentive delay task in which reward, loss and neutral cues were presented. Microstate analysis and standardized low-resolution electromagnetic tomography (sLORETA) were applied to EEG data. Furthermore, analyses correlating a topographic index (the ERPs score), calculated to quantify brain activation in relationship to the microstate maps, and scales assessing hedonic experience and negative symptoms were performed. Alterations in the first (125.0–187.5 ms) and second (261.7–414.1 ms) anticipatory cue-related microstate classes were observed. In SCZ, reward cues were associated to shorter duration and earlier offset of the first microstate class as compared to the neutral condition. In the second microstate class, the area under the curve was smaller for both reward and loss anticipation cues in SCZ as compared to HC. Furthermore, significant correlations between ERPs scores and the anticipation of pleasure scores were detected, while no significant association was found with negative symptoms. sLORETA analysis showed that hypo-activation of the cingulate cortex, insula, orbitofrontal and parietal cortex was detected in SCZ as compared to HC. Abnormalities in ERPs could be traced already during the early stages of reward processing and were associated with the anticipation of pleasure, suggesting that these dysfunctions might impair effective evaluation of incoming pleasant experiences. Negative symptoms and anhedonia are partially independent results.
Introduction
Negative symptoms represent a fundamental aspect of schizophrenia: they have a substantial impact on patients’ real-life functioning and do not respond satisfactorily to currently ...available treatments. Therefore, a better understanding of the pathophysiological mechanisms underlying these symptoms could favor the development of new treatments.
To date, the most validated pathophysiological hypothesis indicates an association between the Motivational domain (consisting of avolition, anhedonia and asociality) and alterations in the neuronal circuits involved in motivation. The Expressive Deficit domain (consisting of blunted affect and alogia) would be subtended by widespread alterations of cortical connectivity and associated with impaired neurocognition, social cognition, and the presence of neurological soft signs.
Objectives
The aim of the present study is to examine the neurobiological correlates of the two domains of negative symptoms, starting from the brain areas that have been most commonly found in the literature to be associated with negative symptoms.
Methods
Resting-state (rs) fMRI data were acquired in 62 subjects with schizophrenia (SZ) and 46 healthy controls (HC). The two negative symptom domains were assessed using the Brief Negative Symptom Scale. In addition, the following assessment tools were used: the Positive and Negative Syndrome Scale for the assessment of positive symptoms and disorganization, the Calgary Depression Scale for Schizophrenia for depression and the St. Hans Rating Scale for extrapyramidal symptoms. The study of the possible relationships between rs-brain activity and the negative symptoms domains was conducted through partial correlations, checking for possible confounding factors (positive, depressive, extrapyramidal symptoms and disorganization).
Results
The SZ, compared to the HC, showed higher rs-brain activity of the right inferior parietal lobule and of the right temporoparietal junction and lower rs-brain activity of the right dorsolateral prefrontal cortex, bilateral anterior dorsal cingulate cortex, bilateral ventral caudate and bilateral dorsal caudate. Furthermore, in the group of patients, the rs-brain activity of the left ventral caudate showed a moderate negative correlation with the Expressive deficit domain (r = -0.401; p = 0.003), but not with the Motivational domain.
Conclusions
The results of the present study, in line with the literature, demonstrated how the two domains of negative symptomatology are subtended by different pathophysiological mechanisms. Given the role played by the ventral caudate in neurocognitive processes, these results are in line with the hypothesis that Expressive deficit may have a common etiopathogenesis with cognitive deficits. A better understanding of the neurobiology of negative symptoms could foster the development of innovative treatment strategies targeting the two negative symptom domains.
Disclosure of Interest
None Declared
Introduction
Negative symptoms (NS) represent an unmet need of treatment in schizophrenia (SCZ). As a result, these symptoms pose a significant burden on patients, their families, and the health care ...system. In the last decade, the conceptualization model that has received the most support from the literature has described 2 domains of NS: the expressive deficit (EXP), which includes blunted affect and alogia, and the motivational deficit (MAP), which includes avolition, asociality, and anhedonia. However, different confirmatory factor-analytic studies suggest that the bi-dimensional model may not capture the complexity of this construct, which could be better defined by the 5-factor model. To date no study exploiting innovative tools and state of the art assessment instruments has yet been conducted to evaluate the NS structure stability over time.
Objectives
The aim of this study was to investigate the stability of the latent structure of NS in subjects with SCZ.
Methods
NS were assessed in 612 subjects with SCZ using the Brief Negative Symptom Scale (BNSS) at the baseline and after 4-year follow-up. A network invariance analysis was conducted for the data collected longitudinally.
Results
Results showed that the BNSS’ items aggregated to form 5 distinct domains (avolition, asociality, blunted affect, alogia and anhedonia). The result of the network invariance test indicated that the network structure remained unchanged over time (network invariance test = 0.13; p = 0.169) while its overall strength decreased significantly (6.28 baseline, 5.79 at follow-up; global strength invariance test = 0.48; p = 0.016).
Conclusions
The results of this study show how the construct of NS can be better explained by the 5 individual negative symptoms and that this model is almost stable over time. Therefore the 2-dimensional model may be insufficient to describe the characteristics of NS. This data is of important relevance with consequent implications in the study of pathophysiological mechanisms and the development of targeted treatments for NS.
Disclosure of Interest
None Declared
Abstract Body
Central to recovery-oriented approaches in schizophrenia are treatment integration and personalization, targeting key variables beyond symptom reduction. The Italian network for ...research on psychoses conducted a study demonstrating, using network analysis, the central role of community activities in bridging the effects of symptoms, cognition, functional capacity and service engagement on real-word functioning. A 4-year follow-up study was recently completed and the presentation will illustrate the findings. Network analysis was used to test whether relationships among all variables at baseline were similar at follow-up. In addition, the network structure was compared between subjects classified as recovered or non-recovered at follow-up. Six hundred eighteen subjects were assessed at both baseline and 4-year follow-up. Results showed that the network structure was stable from baseline to follow-up, and the overall strength of the connections among variables did not significantly change. Functional capacity and everyday life skills were the most central variables in the network at both baseline and follow-up, while psychopathological variables were more peripheral. The network structure of non-recovered patients was similar to the one observed in the whole sample, but very different from that of recovered subjects, showing few connections among the different nodes. These data strongly suggest that connections among symptoms/dysfunctions tend to maintain over time, contributing to poor outcome in schizophrenia. Early treatment plans, targeting variables with high centrality, might prevent the emergence of self-reinforcing networks of symptoms and dysfunctions in people with schizophrenia.
Disclosure
Armida Mucci has been a consultant and/or advisor to or has received honoraria from Gedeon Richter Bulgaria, Janssen Pharmaceuticals, Lundbeck, Otsuka, Pfizer and Pierre Fabre. None of these has any impact on this abstract and on the presented study.
Introduction
Social cognition and skill deficits have been largely documented in subjects with schizophrenia (SCZs), and have a strong influence on the functional outcome of these subjects. Different ...behavioural interventions have been developed to target and improve social skills in SCZs. For instance, the Social Skills Training (SST) focuses on improving communication skills and assertiveness to facilitate disease management, independent living and real-life functioning of SCZs. SST seems also to have an impact on negative symptoms and social cognition.
Objectives
The study aims to evaluate the effectiveness of SST in improving social cognition and negative symptoms in SCZs.
Methods
The sample included 8 chronic SCZs (age between 18 and 60), who completed 6 months of SST. The intervention consisted of two weekly group sessions of 2 hours each. We assessed psychopathology, neurocognition, real-life functioning, functional capacity and social cognition at baseline and after training. Paired samples t-tests were performed to evaluate the differences of the variables considered after completing the treatment.
Results
Significant improvements in negative symptoms (p<.05), social cognition (p<.05), functional capacity (p<.001), activities of daily living (p<.001) and interpersonal relationships (p<.011) were found.
Conclusions
The present findings suggest that SST might ameliorate social cognition and negative symptoms which are generally not influenced by antipsychotic treatment. The integration of pharmacological and SST interventions might have an impact on major determinants of poor real-life functioning in SCZs.
In a cross-sectional study, the Italian Network for Research on Psychoses (INReP) found that variables relevant to the disease, personal resources and social context explain 53.8% of real-life ...functioning variance in a large sample of community dwelling people with schizophrenia. In a longitudinal study, the INReP aimed to identify baseline predictors of main domains of real-life functioning, i.e. work skills, interpersonal relationships and everyday life skills, at 4-year follow-up. We assessed psychopathology, social and non-social cognition, functional capacity, personal resources, and context-related factors, as well as real-life functioning as the main outcome. We used structural equation modeling (SEM) and latent change score (LCS) model to identify predictors of real-life functioning domains at follow-up and changes from baseline in the same domains. Six-hundred-eighteen subjects took part in the study. Neurocognition predicted everyday life and work skills; avolition predicted interpersonal relationships; positive symptoms work skills, and social cognition work skills and interpersonal functioning. Higher neurocognitive abilities predicted the improvement of everyday life and work skills, as well as of social cognition and functional capacity; better baseline social cognition predicted the improvement of work skills and interpersonal functioning, and better baseline everyday life skills predicted the improvement of work skills. Several variables which predict important aspects of functional outcome of people with schizophrenia are not routinely assessed and are not systematically targeted by intervention programs in community mental health services. A larger dissemination of practices such as cognitive training and personalized psychosocial interventions should be promoted in mental health care.
Disclosure
No significant relationships.
Introduction
Cognitive deficits are considered a key feature of schizophrenia due to their substantial influence on the psychosocial outcome of subjects affected by this disorder. Several studies ...showed that moderate to severe cognitive impairments, including dysfunctions of social cognition, are already present during the early phases of the illness, in subjects with first-episode psychosis (FEPs). Psychosocial interventions, such as social skill training (SST), could therefore be implemented already upon occurrence of the first episode of psychosis to improve the overall functional outcome of schizophrenia, which represents to date an unmet need in the care of these patients.
Objectives
The study aims to evaluate the use of SST to enhance social skills and real-life functioning in FEPs.
Methods
The sample included 7 FEPs (age between 15 and 40). The SST intervention included 30 sessions lasting 2 hours and delivered twice a week. Psychopathology, neurocognition, real life functioning, functional capacity and social cognition were assessed at baseline ad after training. Paired samples t-tests were performed to evaluate the effects of the intervention. All subjects were treated with second generation antipsychotics.
Results
Significant improvements were observed in negative symptoms, social cognition, problem solving skills, as well as in global functioning (all p<0.05). Within real-life functioning, the improvement was greater for the domain of interpersonal relationships.
Conclusions
These preliminary findings suggest that SST might complement pharmacological treatment in FEPs to improve functional outcome in these subjects. Further studies with a higher sample size and a longer follow-up are required in order to confirm the present results.
Introduction
Negative symptoms (NS) represent a core aspect of schizophrenia with a huge impact on real life functioning. Dysfunctions within the dopaminergic cortico-striatal circuits have been ...documented in subjects with schizophrenia (SCZ) and hypothesized as possible neurobiological mechanisms underlying some domains of NS.
Objectives
We investigated relationships between the resting-state functional connectivity (RS-FC) of the ventro-tegmental area (VTA) and NS.
Methods
Resting-state fMRI data were recorded in 35 SCZ, recruited within the Italian Network for Research on Psychoses. We performed partial correlations between RS-FC and NS (evaluated with the Brief Negative Symptom Scale) controlling for possible sources of secondary negative symptoms.
Results
We found that the experiential domain correlated with the RS-FC of the VTA with the left ventro-lateral prefrontal cortex (lVLPFC) (r=0.372, p=0.039), while the Expressive deficit domain correlated with the RS-FC of the VTA with the left dorso-lateral prefrontal cortex (lDLPFC) (r= 0.470, p .008). Looking at subdomains, only the avolition (r= 0.418, p=0.019) and the blunted affect (r= 0.465, p=.008) showed the same correlations of the domains to which they belong.
Conclusions
According to our findings, separate dysfunctional neuronal circuits could underpin distinct negative symptom subdomains. A better understanding of neurobiological dysfunctions underlying NS could help to design new treatments, targeting different NS subdomains.
Highlights • Subjects with schizophrenia are unable to integrate the incentive magnitude and reward value of future events as studied by the P3 response in event-related potentials. • Avolition and ...expressive deficits are not related to P3 amplitude. • These findings might foster the development of innovative rehabilitation treatments in schizophrenia.
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