Laura Bianchi

Plasma tryptophan levels and tryptophan/neutral amino acid ratios in obsessive-compulsive patients with and without depression

We have studied fasting plasma tryptophan (TRP) levels and tryptophan/large neutral amino acid (TRP/LNAA) ratios in 12 patients with obsessive-compulsive disorder (OCD) and 12 patients with OCD and a coexisting current diagnosis of major depressive disorder (OCD-MDD). Assessments were made at baseline and after 6 weeks of treatment with fluvoxamine. OCD-MDD patients had significantly lower baseline TRP levels and TRP/LNAA ratios than OCD patients. After 6 weeks of fluvoxamine treatment, OCD-MDD patients had significant increases in plasma TRP and TRP/LNAA ratio, whereas OCD patients had non-significant decreases. Our data suggest that a major depressive syndrome could be a state variable affecting the changes in plasma TRP and TRP/LNAA ratio in OCD patients.

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

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.

Emotional reactivity in referred youth with disruptive behavior disorders: The role of the callous-unemotional traits

Deficits in emotional reactivity are frequently reported in Disruptive Behavior Disorders (DBDs). A deficit in prosocial emotions, namely the callous unemotional traits (CU), may be a mediator of emotional reactivity. Our aim is to investigate subjective emotional reactivity towards visual stimuli with different affective valence in youths with DBDs and healthy controls. The clinical sample included 62 youths with DBDs (51 males, 8 to 16 years, mean 11.3±2.1 years), the control group 53 subjects (36 males, 8 to 16 years, mean 10.8±1.5 years). The groups were compared using the Child Behavior Checklist (CBCL), the Inventory of Callous-Unemotional Traits (ICU), and the International Affective Picture System (IAPS), which explores the affective (pleasant/unpleasant emotional reaction) and arousal (low/high intensity of emotion) dimensions. The DBD group presented higher scores in externalizing and internalizing CBCL scores, and in ICU callous and indifferent subscales. At the IAPS, DBD patients differed from controls in the affective valence of the images, rating less unpleasant neutral and negative images. The CU traits were the only predictor of emotional reactivity in the DBD sample. A less aversive way to interpret neutral and negative stimuli may explain why DBD patients are less responsive to negative reinforcements.

Cognitive remediation and functional improvement in schizophrenia: Is it a matter of size?

BACKGROUNDnCognitive Remediation represents the best available tool to treat cognitive deficits in schizophrenia and evidence suggests an effect also on global functioning. However, the relationship between cognitive and functional improvement is not yet fully elucidated: do cognitive changes need to be of a definite size and/or encompass a certain number of domains in order to impact on daily functioning? This study aims to explore the role of cognitive improvement, evaluated both quantitatively and qualitatively through the use of Italian equivalent scores, on the daily functioning of patients. As secondary goal, the influence of demographic, clinical and neuropsychological variables on functional outcome was also systematically investigated.nnnMETHODSnOne hundred subjects with a diagnosis of schizophrenia underwent 36xa0sessions of Cognitive Remediation and were evaluated at baseline and after the training with the Brief Assessment of Cognition in Schizophrenia and the Quality of Life Scale.nnnRESULTSnA total of 70% of patients improved in at least one cognitive domain and over 50% obtained a normalized score. Among the clinical and neurocognitive factors examined, the only significant predictor of quality of lifes improvement was the proportion of cognitive functions that reached an equivalent score of normal.nnnCONCLUSIONSnThis study suggests that improvements in daily functioning depend on the achievement of a cognitive profile as much as possible normal, harmonious and balanced, supporting the idea that a qualitative leap in cognition is needed in order to gain an advantage in real life activities.

Anticipation of age at onset of obsessive-compulsive spectrum disorders in patients with obsessive-compulsive disorder

Anticipation of age at onset has been observed in several neuropsychiatric disorders. Recent studies have associated anticipation with the presence of unstable DNA and have suggested that trinucleotide repeats may be the main cause in some of these diseases. However, several selection biases may mimic the presence of such an effect. In this study we evaluated the presence of this effect in 40 families of probands with obsessive-compulsive disorder (OCD) compared with affected subjects in the parental generation. We controlled for ascertainment biases by taking into account the age at interview of probands. Using a different recruitment strategy, we controlled for anticipation in a sub-sample of offspring of 13 OCD patients, affected with OC spectrum disorders. While the younger generation showed a significantly earlier age at onset than the parental generation, no effect of age at interview was observed. Drawing on the results, we hypothesised that the presence of anticipation in OCD and OC spectrum disorders could be due to a specific genetic effect (unstable DNA), as it has been hypothesised for other disorders showing this effect.

Visual and audio emotion processing training for outpatients with schizophrenia: an integrated multisensory approach

ABSTRACT Deficits in emotion processing (EP) represent a target of rehabilitation in schizophrenia, as they have been related to poor personal and social functioning. To date neither the relationship between these deficits and the generalised cognitive impairment, nor the involvement of specific mechanisms of perception (visual or auditory) are fully comprehended. We developed two treatments targeting EP, through visual or auditory channels, with the aim of disentangling possible differences and/or interactions between the two modalities in schizophrenia-related impairments, also taking into account the role of cognition and social functioning. Thirty five outpatients with schizophrenia were assessed for neurocognition, social functioning and EP (visual and auditory channel) and participated in either visual or auditory EP training or in an active control group. Results showed a significant improvement in EP through the specific channel trained for both groups, with an extended effect also on vocal stimuli for the visual training group. Positive correlations were found between working memory, social functioning and EP. Our findings help to shed light on the possible different involvement of perceptual channels in schizophrenia, as well as supporting previous evidence that emotion recognition may be inter-related but does not overlap with neurocognition and can be specifically trained.

Intellectual and cognitive profiles in patients affected by schizophrenia

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.

Is longer treatment better? A comparison study of 3 versus 6 months cognitive remediation in schizophrenia.

Objective: Despite its extensive use for treating cognitive deficits in schizophrenia, computer-assisted cognitive remediation (CACR) currently lacks a standardized protocol. Duration is an important feature to be defined, as it may contribute to heterogeneous outcome. This study compares 2 treatment durations, 3 versus 6 months, to analyze their effects on both cognition and daily functioning. Method: Fifty-seven outpatients with schizophrenia received 3 months of CACR and 41 received 6 months of CACR. All patients were assessed at baseline and after 3 and 6 months with the Brief Assessment for Cognition in Schizophrenia and with the Quality of Life Scale (QLS). Results: Repeated measures ANOVA showed significant improvements in all cognitive domains after 3 months. A significant effect of treatment duration was observed only for executive functions, with significantly higher scores among patients treated for 6 months. Significant improvements in QLS were also observed after 6 months in both groups, with a significant time by treatment interaction for QLS Total Score. Conclusions: Results confirm the efficacy of 3-months CACR in terms of both cognitive and functional improvements, suggesting that an extended intervention may lead to further benefits in executive functions and daily functioning.

Targeting anxiety to improve quality of life in patients with schizophrenia

BACKGROUNDnSeveral studies suggested that anxiety can significantly affect the outcome of schizophrenia. Despite this evidence, non-pharmacological interventions targeting anxiety are still heterogenous. This study aims to test the efficacy of a novel training specifically designed to target anxiety in patients with schizophrenia. Innovatively, this training, beyond psychoeducation and problem solving, also targets Theory of Mind, as it provides coping strategies.nnnMETHODnTwenty-seven outpatients with schizophrenia received a novel rehabilitative training targeting anxiety (Anxiety Management Group [AMG]) combined with a Computer-Assisted Cognitive Remediation (CACR), and twenty received CACR plus a control intervention (Control Newspaper discussion Group [CNG]). All patients were assessed at baseline and after treatment for quality of life, neurocognition and anxiety.nnnRESULTSnAfter training, patients treated with AMG+CACR showed significantly greater improvements on anxiety. A significant increase in quality of life was observed only for AMG+CACR group. Moreover, the participants appraisal showed a significant difference between treatment groups with higher ratings among patients who received the AMG+CACR.nnnCONCLUSIONSnThis study thus suggests feasibility and efficacy of the proposed intervention, that could be implemented in rehabilitative programs for patients with schizophrenia with potential benefits also on disease course and outcome.

Neurobiology of cognitive remediation in schizophrenia: Effects of EAAT2 polymorphism

Cognitive deficits represent core features of schizophrenia, affecting quality of life and functioning. The excitatory amino acid transporter 2 (EAAT2) is responsible for the majority of glutamate reuptake and its activity is crucial for glutamatergic neurotransmission, prevention of excitotoxic damage and cerebral metabolism. Different studies reported that EAAT2 rs4354668 (-181u202fT/G) influences cognitive functions and brain structures in patients with schizophrenia. Specifically, the G allele, linked to lower EAAT2 expression, was associated with impaired prefrontal cognitive performance and reduced grey matter volumes. Cognitive remediation therapy (CRT) is one of the best available tool to treat cognitive deficits in schizophrenia, able to induce a neuroplastic modulation of cognitive functions. The present study aims to investigate the effects of rs4354668 on CRT outcome, also considering possible genotype interaction with antipsychotic (AP) treatment, since EAAT2 expression is negatively influenced by clozapine. We examined rs4354668 in 88 clinically stabilized patients with schizophrenia, treated with CRT and assessed at enrolment, at the end of CRT and after 3u202fmonths. We observed greater working memory improvements among patients carrying the T/T genotype, regardless of AP treatment. Moreover, we reported a significant interaction between pharmacological treatment and rs4354668 on executive functions, with greater improvements among T/T patients treated with APs other than clozapine. These observations suggest that impaired EAAT2 expression may attenuate CRT outcome. Moreover, our results indicate the possibility that rs4354668 could also differentially influence the response to CRT depending on the AP treatment.