Publications by authors named "Giulia Agostoni"

11 Publications

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Functional benefits of co-occurring autistic symptoms in schizophrenia is delimited by symptom severity.

J Psychiatr Res 2021 Feb 22;137:48-54. Epub 2021 Feb 22.

Schizophrenia Research and Clinical Unit, Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Psychology, Vita-Salute San Raffaele University, Milan, Italy.

Background: Impairments in daily functioning characterize both autism spectrum disorder and schizophrenia. Research has shown that a subsample of schizophrenia patients presents autistic symptoms, leading to the hypothesis that their co-occurrence would be associated with a 'double dose' of deficit. A growing body of research examined this hypothesis by looking at the joint effect of autistic and positive psychotic symptoms, and yielded contrasting results, ranging from benefits to adverse effects. We hypothesized that the interactive effect of autistic and positive symptoms on functioning in schizophrenia might depend on the patients' symptom severity.

Method: In 170 schizophrenia patients, a two-step cluster analysis identified two groups of patients with different levels of autistic and positive symptom severity. Using general linear models, we examined the interactions of groups, autistic and positive symptoms on functioning.

Results: Autistic and positive symptoms were interactively associated with better functioning, but only in the symptomatically less severe patients. In contrast, autistic and positive symptoms were independently associated with worse functioning in the symptomatically more severe patients. These associations were observed above and beyond the effects of I.Q. and illness duration.

Conclusions: The findings highlight the complex role played by co-occurring autistic symptoms in schizophrenia, whose beneficial effects on functioning appear to depend on patients' psychopathological severity. Our findings may help to reconcile the seemingly contrasting results from previous studies, and to understand the heterogeneity of behavior and functional outcomes in schizophrenia. This study underscores the potential utility of routinely assessing autism in schizophrenia, in order to better formulate individualized rehabilitative programs.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.044DOI Listing
February 2021

Clozapine tolerability in Treatment Resistant Schizophrenia: exploring the role of sex.

Psychiatry Res 2021 Mar 30;297:113698. Epub 2020 Dec 30.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Clozapine is the only evidence-based drug indicated for Treatment Resistant Schizophrenia but it is largely underprescribed, partially due to its life-threatening adverse effects (AEs). However, clozapine treatment is burdened by other common AEs as constipation, hypersalivation, postural hypotension, tachycardia and metabolic abnormalities. Few studies have investigated sex-related differences in clozapine's tolerability, reporting women to experience more frequently weight gain, hyperglycemia and constipation, while men hypertension and dyslipidemia. Based on these premises, we investigated clinical, psychopathological and metabolic sex-related differences among 147 treatment-resistant patients treated with clozapine, with a specific focus on non-life-threatening AEs. We observed significant higher prevalence of tachycardia in men, and of orthostatic hypotension and constipation in women. Concerning metabolic alterations, we observed significant lower levels of HDL-cholesterol and higher prevalence of hypertriglyceridemia among men, whereas females showed higher prevalence of abdominal obesity. Consistently with previous studies, our data confirm the presence of sex-related differences in clozapine tolerability, with a main effect of sex especially for tachycardia, postural hypotension and constipation. Although non-life-threatening, these common AEs significantly affect patients' quality of life, undermine compliance and cause treatment discontinuation. A better understanding of this topic could contribute to tailor therapeutic approaches, thus improving tolerability, compliance and clinical stability.
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http://dx.doi.org/10.1016/j.psychres.2020.113698DOI Listing
March 2021

Communicative-pragmatic abilities mediate the relationship between cognition and daily functioning in schizophrenia.

Neuropsychology 2021 Jan;35(1):42-56

School of Medicine, Vita-Salute San Raffaele University.

Objective: Pragmatics refers to the capacity to understand the speaker's meaning and thus to appropriately engage in a conversation. This study aims at establishing the role of communicative-pragmatic abilities in functioning, defined as a set of daily activities, in schizophrenia. This would contribute to enrich current models of the neurocognitive predictors of functioning, which have so far neglected pragmatics.

Method: One hundred people with schizophrenia underwent a comprehensive assessment including functioning, cognition, theory of mind (ToM), and pragmatics. We tested the effects of cognition as a predictor of functioning, first mediated by ToM, then sequentially mediated by ToM and pragmatics. Next, we explored the predictive effect of cognition, sequentially mediated by ToM and pragmatics, on different functional domains (i.e., interpersonal relations, instrumental role, and personal autonomy).

Results: The first model confirmed that ToM acts as a mediator between cognition and functioning. Importantly, the second model highlighted also the main mediating role of pragmatics. The mediation models on different functional domains showed that, when considered together, both pragmatics and ToM significantly influenced all aspects of functioning. When considered separately, pragmatics was significantly related to interpersonal functioning, while ToM to personal autonomy.

Conclusions: Innovatively, our findings highlight that pragmatics has a main role, both direct and indirect, in affecting functioning. Of particular interest is that the impact of pragmatics encompasses different functional domains, and especially interpersonal functioning. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/neu0000664DOI Listing
January 2021

Cognitive Remediation for Inpatients With Schizophrenia: Effects of a Brief and Intensive Training.

J Nerv Ment Dis 2021 01;209(1):76-81

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute.

Computer-assisted cognitive remediation (CACR) is a computer-based rehabilitation treatment aimed at improving cognition and at developing strategies that can be applied to various functional areas. Different protocols are currently used with great variability over the intensity and duration of treatments. In this study, we evaluated the effects of a brief and intensive CACR training (i.e., 15 sessions for 3 weeks) on cognitive domains, as well as the durability of cognitive gains and their generalization to functional areas, 3 months after CACR training. Thirty-eight patients with schizophrenia were recruited and assessed for psychopathology, cognitive performance, and functioning before the rehabilitative intervention. Patients were reassessed for cognition after CACR rehabilitation. Moreover, a subsample of 13 patients was evaluated for cognition and functioning 3 months after CACR completion. Results show significant improvements in multiple cognitive domains after CACR. Furthermore, 3 months after CACR completion, significant improvements were also detected in executive functions and daily functioning. This study suggests that a brief and intense CACR training is effective on cognitive and functional domains and that it could be feasible and affordable for health care services, thus offering patients the best options for fulfilling recovery goals.
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http://dx.doi.org/10.1097/NMD.0000000000001262DOI Listing
January 2021

The role of agency in schizophrenia: A pilot study on gaze agency.

Schizophr Res 2020 Aug 28;222:465-466. Epub 2020 Jun 28.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

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http://dx.doi.org/10.1016/j.schres.2020.06.025DOI Listing
August 2020

The association of autistic traits with Theory of Mind and its training efficacy in patients with schizophrenia.

Schizophr Res Cogn 2020 Mar 31;19:100164. Epub 2019 Oct 31.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Literature has recently identified a discrete subgroup of patients affected by schizophrenia that also present autistic traits (ATs), showing a peculiar cognitive, clinical and functional profile. Theory of Mind (ToM) represents a core, impaired feature in both schizophrenia and Autism Spectrum Disorder (ASD), ToM in patients with schizophrenia and ATs has yet to be investigated. Thus, this study aims, on the one hand, to assess differences among patients with and without ATs on clinical, cognitive and ToM abilities as well as in daily functioning; on the other hand, to compare the efficacy on mentalizing abilities of a specific ToM training in these two groups. Ninety-six patients with schizophrenia were enrolled and underwent a broad cognitive, social-cognitive and functional assessment before and after the ToM training. ANOVAs revealed that patients with schizophrenia and ATs are more impaired in cognition, ToM, in premorbid and daily functioning as well as in clinical features, as compared to patients without ATs. This latter group also showed a general improvement in mentalizing abilities after ToM training, while patients with schizophrenia and ATs did not, with a significant time × group interaction on ToM abilities. These data shed new light on the relation among schizophrenia and ATs, highlighting that patients with these traits are highly impaired in ToM abilities. Thus, ATs seem to limit the effectiveness of ToM training, having implications in clinical and rehabilitative practice.
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http://dx.doi.org/10.1016/j.scog.2019.100164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6890977PMC
March 2020

The Influence of Premorbid Adjustment and Autistic Traits on Social Cognitive Dysfunction in Schizophrenia.

J Int Neuropsychol Soc 2020 03 11;26(3):276-285. Epub 2019 Sep 11.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, 20100, Italy.

Objectives: Premorbid dysfunction during childhood and adolescence is well documented in patients with schizophrenia. Literature pointed out multiple premorbid trajectories leading to different patients' cognitive status, symptomatology, and global functioning after disease onset. This study aimed at identifying groups of premorbid trajectories and disentangling between group differences in clinical and cognitive measures, focusing on theory of mind (ToM) and autistic traits (ATs).

Methods: Ninety-seven patients with schizophrenia were recruited and assessed for cognitive and ToM abilities, psychopathology, and ATs. A two-step cluster analysis identified three different groups of patients based on premorbid adjustment during childhood, adolescence, and late adolescence (i.e., stable-good, stable-poor, and "deteriorating").

Results: Compared to 66 healthy controls, results showed a widespread impairment in cognitive and ToM abilities among all groups of patients, except for affective ToM and executive functions in the stable-good group. Moreover, the stable-poor group exhibited more pronounced ATs and a more severe ToM impairment, compared to the other two groups of patients.

Conclusions: Our findings highlight the existence of a group of patients with poor premorbid adjustment since childhood, more pronounced ATs and a severe ToM impairment affecting those basic mentalizing skills that are usually preserved in schizophrenia. Results might have intriguing implications in identifying underpinning endophenotypes and implementing cutting-edge rehabilitation programs.
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http://dx.doi.org/10.1017/S1355617719000961DOI Listing
March 2020

Stability and generalization of combined theory of mind and cognitive remediation interventions in schizophrenia: Follow-up results.

Psychiatr Rehabil J 2020 Jun 15;43(2):140-148. Epub 2019 Aug 15.

Department of Clinical Neurosciences.

Objective: Daily functional impairment is a main target of treatment in schizophrenia. Multiple rehabilitation treatments have been developed to improve patients' sociocognitive and neurocognitive abilities and to generalize the benefits to functioning. However, whether the effects of these treatments can be generalized and maintained remains equivocal. Our study aims to evaluate the stability and generalization of benefits, following combined Theory of Mind (ToM) and cognitive remediation (CR) trainings, compared with an active control group + CR, at a 3-year follow-up.

Method: Sixty-seven outpatients with schizophrenia who had completed an earlier study of ToM and CR were recruited for a 3-year follow-up assessment. We examined changes in ToM and functioning, at baseline, after treatment, and at follow-up.

Results: ANOVAs showed significant Time × Group interactions on ToM and functioning. ANOVAs showed significant differences between groups in effect sizes of ToM and functioning from before treatment to follow-up.

Conclusions And Implications For Practice: Posttraining ToM improvement was maintained at follow-up, and ToM + CR participants experienced greater functional improvement than participants in the control condition. This study represents the first attempt to report the stability and generalization of treatment effects obtained by combining CR and ToM interventions after 3 years. Combined sociocognitive and neurocognitive treatments can enhance rehabilitation practice for people with schizophrenia to achieve good results on both cognitive and functional outcomes and to maintain positive outcomes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/prj0000379DOI Listing
June 2020

Can patients with schizophrenia have good mentalizing skills? Disentangling heterogeneity of theory of mind.

Neuropsychology 2018 Sep 7;32(6):746-753. Epub 2018 Jun 7.

Department of Clinical Neurosciences.

Objective: Theory of Mind (ToM) is a multifaceted construct that involves mental states attribution in social interactions. Patients with schizophrenia are impaired in ToM abilities, but recent studies showed that a non-negligible number of patients perform within normal ranges or close to normal, whereas other patients are very impaired in ToM tasks. The present study aims to comprehensively analyze differences between patients with "poor" and "fair" mentalizing abilities, as identified through a median-split procedure on mental state attribution task, and healthy controls, as well as to explore the role of clinical, demographical, and neurocognitive predictors of ToM performance within groups.

Method: One hundred twenty-two patients with schizophrenia and 67 healthy controls were assessed for ToM, attention, and executive functioning. In addition, patients' daily functioning and psychopathological profiles were also rated.

Results: "Fair" mentalizers perform significantly better than "poor" mentalizers on cognitive abilities and quality of life and they differ from healthy controls in neurocognition and cognitive ToM performance, even though the global ToM performance is similar. Furthermore, regression models showed distinct contributing factors in each sub group: ToM is related to neurocognitive abilities and education in healthy subjects, while it is mainly associated with attention in "fair" group and it is related to clinical variables and executive functions in "poor" mentalizers.

Conclusions: Although preliminary, these data shed new light on the heterogeneity of ToM deficit among patients with schizophrenia and could reflect on daily clinical practice, as they are important to develop individualized step-by-step rehabilitative programs. (PsycINFO Database Record
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http://dx.doi.org/10.1037/neu0000456DOI Listing
September 2018

Intellectual and cognitive profiles in patients affected by schizophrenia.

J Neuropsychol 2019 09 23;13(3):589-602. Epub 2018 Apr 23.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Intellectual abilities display high heterogeneity in patients with schizophrenia that might depend on the interaction among neurodevelopmental processes, environmental factors and neurocognitive decline. This study aimed to disentangle the interplay between intellectual level, cognitive status and each cognitive domain, with a focus on speed-related abilities, also including pre-morbid factors. In details, by means of cluster analysis, we identified both in global sample of 452 patients affected by schizophrenia and in a subsample with high pre-morbid functioning, different profiles based on current intellectual level and global cognitive status, analysing the distribution of deficits in each cognitive domains between groups. Then, through regression models, we analysed the contribution of speed-related domains and global cognitive profile to each other cognitive function. Considering the whole sample, results highlight three groups (high, medium and low cognitive level), while among patients with high pre-morbid level, the heterogeneity was best captured by two groups (high and medium level). Still, within each group, a small to high percentage of patients achieved normal score in neurocognitive abilities depending on the cluster they belong to. Speed of processing and psychomotor coordination resulted impaired in all clusters, even in patients with high pre-morbid functioning. The regression analyses revealed significant effects of both cognitive profile and speed-dependent domains on the other cognitive abilities. This study confirms, in a large sample, previous data about the heterogeneity of intellectual and neurocognitive functioning in schizophrenia and highlights the main role of speed-dependent neurocognitive functioning, also as an important target of rehabilitation.
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http://dx.doi.org/10.1111/jnp.12161DOI Listing
September 2019

Exploring functioning in schizophrenia: Predictors of functional capacity and real-world behaviour.

Psychiatry Res 2017 May 9;251:118-124. Epub 2017 Feb 9.

Department of Clinical Neurosciences, IRCCS San Raffaele Scientific Institute, Milan, Italy; Università Vita-Salute San Raffaele, Milan, Italy.

Impairment in daily functioning still represents a major treatment issue in schizophrenia and a more in-depth knowledge of underlying constructs is crucial for interventions to translate into better outcomes. This study aims to model factors influencing both functional capacity and real-life behaviour in a sample of outpatients with chronic schizophrenia, through a comprehensive assessment including evaluations of psychopathology, cognitive and social cognitive abilities, premorbid adjustment, family environment and early childhood experiences. No significant correlation was observed between functional capacity and real-life behaviour. Functional capacity was significantly predicted by IQ, while real-life behaviour was significantly predicted by empathy, affect recognition and symptoms. Functional capacity seems mainly related to neurocognition, whereas real-life behaviour appears more complex, requiring the integration of different factors including symptoms, with a major role of empathy. Results thus support a divergence between the two constructs of functioning and their underlying components and highlight the need to target both dimensions through individualized sequential rehabilitation programs in order to optimize functional outcome.
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http://dx.doi.org/10.1016/j.psychres.2017.02.019DOI Listing
May 2017