S. Galderisi

The influence of illness-related variables, personal resources and context-related factors on real-life functioning of people with schizophrenia.

In people suffering from schizophrenia, major areas of everyday life are impaired, including independent living, productive activities and social relationships. Enhanced understanding of factors that hinder real‐life functioning is vital for treatments to translate into more positive outcomes. The goal of the present study was to identify predictors of real‐life functioning in people with schizophrenia, and to assess their relative contribution. Based on previous literature and clinical experience, several factors were selected and grouped into three categories: illness‐related variables, personal resources and context‐related factors. Some of these variables were never investigated before in relationship with real‐life functioning. In 921 patients with schizophrenia living in the community, we found that variables relevant to the disease, personal resources and social context explain 53.8% of real‐life functioning variance in a structural equation model. Neurocognition exhibited the strongest, though indirect, association with real‐life functioning. Positive symptoms and disorganization, as well as avolition, proved to have significant direct and indirect effects, while depression had no significant association and poor emotional expression was only indirectly and weakly related to real‐life functioning. Availability of a disability pension and access to social and family incentives also showed a significant direct association with functioning. Social cognition, functional capacity, resilience, internalized stigma and engagement with mental health services served as mediators. The observed complex associations among investigated predictors, mediators and real‐life functioning strongly suggest that integrated and personalized programs should be provided as standard treatment to people with schizophrenia.

Inhibition of auditory cortical responses to ipsilateral stimuli during dichotic listening: evidence from magnetoencephalography

The present magnetoencephalography (MEG) study on auditory evoked magnetic fields (AEFs) was aimed at verifying whether during dichotic listening the contralateral auditory pathway inhibits the ipsilateral one, as suggested by behavioural and patient studies. Ten healthy subjects were given a randomized series of three complex tones (261, 293 and 391u2003Hz, 500u2003ms duration), which were delivered monotically and dichotically with different intensities [60, 70 or 80u2003dBA (audio decibels)]. MEG data were recorded from the right auditory cortex. Results showed that the M100 amplitude over the right auditory cortex increased progressively when tones of increasing intensity were provided at the ipsilateral (right) ear. This effect on M100 was abolished when a concurrent tone of constant intensity was delivered dichotically at the contralateral (left) ear, suggesting that the contralateral pathway inhibited the ipsilateral one. The ipsilateral inhibition was present only when the contralateral tone fundamental frequency was similar to the ipsilateral tone. It was proposed that the occlusion mechanism would be exerted in cortical auditory areas as the dichotic effects were observed at M100 but not M50 component. This is the first evidence showing a neurophysiological inhibition driven by the contralateral auditory pathway over the ipsilateral one during dichotic listening.

Is avolition in schizophrenia associated with a deficit of dorsal caudate activity? A functional magnetic resonance imaging study during reward anticipation and feedback

Background The neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia. Method We used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation. Results The whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group. Conclusions These findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.

Induced Gamma Activity and Event-Related Coherence in Schizophrenia

Evidence has been provided that high frequency oscillations within the gamma band reflect mechanisms of cortical integration. In the light of recently proposed pathophysiological models of schizophrenia, suggesting a disturbance of the functional connectivity within distributed neural networks, it has been hypothesized that abnormalities in the gamma band underlie perceptual and cognitive dysfunctions in patients with schizophrenia. In the present study we investigated evoked and induced 40-Hz gamma power as well as frontoparietal and frontotem-poral event-related coherence in patients with deficit and nondeficit schizophrenia and in matched healthy controls. In patients, correlations between gamma oscillations and psychopathological dimensions were also investigated. A reduction of both induced gamma power and event-related coherence was observed in patients with nondeficit schizophrenia, but not in those with deficit schizophrenia. Our findings support the hypothesis that deficit and nondeficit schizophrenia represent separate disease entities, suggesting the presence of a poor integration of the neuronal activity within distributed neural network only in the subgroup of schizophrenic patients without primary and persistent negative symptoms. Associations between an excess of gamma oscillations and psychopathological dimensions were observed, suggesting that abnormal thoughts, behaviors and perceptions might be related to the formation of inappropriate neural connections.

Lateralization patterns of verbal stimuli processing assessed by reaction time and event-related potentials in schizophrenic patients

Event-related potentials (ERPs), reaction time (RT), number of errors and number of omissions were recorded by using a visual target detection paradigm in which consonant pairs were presented in a central and in a lateral condition. Fourteen DSM III drug-free schizophrenics and 19 healthy subjects took part in the study. All of them were male and right-handed. Independent principal component analysis and varimax rotation were performed for each condition. Separate ANOVAs were performed on factor scores computed for each rotated principal component. In the central condition, schizophrenic patients showed a reduction of the late positive complex (LPC) peak with respect to normal controls, and this reduction was associated with a predominant negative symptomatology. No pattern of lateral asymmetry was found in either group for behavioural and ERP measures. For the lateral condition, a significant advantage of the right visual field (RVF) presentation (shorter RT and larger LPC peak for RVF stimuli) was observed in normal subjects, while no visual field effect on these two measures was detected in schizophrenics. Significant differences were found between the two groups on both behavioural and ERP measures for the RVF only. Furthermore, two ERP components showed a marked advantage of the left visual field in the patient group, associated with a predominance of positive symptoms in the clinical picture.

Lateralization patterns of event-related potential and performance indices in schizophrenia: relationship to clinical state and neuroleptic treatment

In a previous study we assessed lateralization patterns of verbal stimuli processing, by means of behavioural and neurophysiological measures, in a sample of drug-free schizophrenics and one of normal controls. The main findings obtained were the following: (1) a right visual field (RVF) advantage on reaction time (RT) and late positive complex (LPC) peak of the ERPs in normal subjects but not in schizophrenics; (2) a left visual field (LVF) significant advantage on P360 and slow wave (SW) amplitude in schizophrenics but not in controls; (3) a significantly longer RT and smaller P360 and SW for RVF stimuli in schizophrenics as compared to normals; (4) a significant contralateral effect of visual field on N180 at both the left and the right parietal site in normal controls and only at the right parietal site in schizophrenics. As a further step of this investigation we re-tested 9 schizophrenics after 28 days of haloperidol treatment. The post-treatment lateralization pattern of verbal stimuli processing was characterized by a RVF advantage on LPC peak amplitude and no visual field effect on P360 and SW, resembling the normal group pattern. Moreover, the N180 amplitude was found to be reduced. Relationships between lateralization pattern and clinical picture changes induced by haloperidol treatment are discussed.

The interrelation of needs and quality of life in first-episode schizophrenia

The interrelation between needs for care and quality of life has been described and replicated by several studies. The present work aims to add to the understanding of longitudinal interrelations between needs for care, quality of life, and other outcome measures by analyzing a sample of patients at the onset of schizophrenia. This study relied on data from the EUFEST trial, designed to compare first- and second-generation antipsychotics during 1xa0year. At baseline, 498 patients have been included. The first (baseline) and the last assessment (12xa0months after baseline) were used for the analyses. Predictors of quality of life were determined using regression analyses. We tested the complex longitudinal interrelations between baseline and outcome measures with structural equation models. Unmet needs were not definitively confirmed as a predictor of subsequent quality of life, unless unmet needs changing to no needs were separated from unmet needs changing to met needs. Each unmet need that changed to no need enhanced the quality of life (mean score 1–7) by 0.136 scale points. This study suggests that when studying quality of life and needs for treatment, it is crucial to differentiate whether unmet needs disappeared or whether they were met, as the former has a stronger impact on quality of life.

Investigation of endocannabinoid system genes suggests association between peroxisome proliferator activator receptor-α gene (PPARA) and schizophrenia

Schizophrenia (SZ) is a complex psychiatric disorder with a large genetic burden and an estimated hereditability of 80%. A large number of neuroanatomical and psychopharmacological studies suggest a central role of the endocannabinoid (eCB) system in the susceptibility of the disease. To further investigate this hypothesis, we performed an association study with genes codifying for key elements of the eCB system in a sample of 170 schizophrenic patients and 350 healthy controls of Italian ancestry. A total of 57 Tag SNPs (tSNPs) were selected using HapMap CEU population SNP database spanning the following genes: cannabinoid receptor 1 (CNR1), peroxisome proliferator activator receptor-α (PPARA), fatty acid amide hydrolase (FAAH) and N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD). Seven out of the 32 tSNPs within PPARA (rs4253765, rs4263776, rs6007662, rs1800206, rs4253763, rs6008197 and rs4253655) and 3 out of 12 tSNPs within CNR1 (rs1049353, rs7766029 and rs806366) were nominally associated with SZ (uncorrected p<0.05). The same pattern of association was observed in the genotype analysis, with rs4253765 showing the highest level of significance (uncorrected p=2×10(-3)). None of these associations survived after permutation test. Our findings suggest a potential role for PPARA in the susceptibility to SZ, but further studies on larger independent samples are warranted in order to clarify the involvement of this gene in the pathophysiology of SZ.

Influence of moclobemide on cognitive functions of nine depressed patients: pilot trial with neurophysiological and neuropsychological indices.

Quantitative electroencephalogram (QEEG) changes induced by the acute administration of moclobemide (200 mg) in patients with major depression include a transient increase in theta-activity, a slight augmentation of alpha-activity and a sustained increase in beta-activity. This QEEG profile distinguishes moclobemide from sedative antidepressants. A 42-day treatment with 400 mg/day of the drug produces a significant decrease in the late positive-complex peak latency of the event-related potentials, suggesting a positive effect on attention and cognitive functions.

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.