L. Oldani

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.

The noradrenergic action in antidepressant treatments: pharmacological and clinical aspects.

Even though noradrenaline has been recognized as one of the key neurotransmitters in the pathophysiology of major depression (MD), noradrenergic compounds have been less extensively utilized in clinical practice, compared to selective serotonin reuptake inhibitors (SSRIs). The development of the first selective noradrenergic reuptake inhibitor (NRI), Reboxetine, has not substantially changed the state of the art. In addition, Atomoxetine, a relatively pure NRI used for the treatment of ADHD, has shown mixed results when administered in augmentation to depressed subjects. Through a Medline search from 2000 to 2010, the present article provides an updated overview of the main pharmacological and clinical aspects of antidepressant classes that, partially or selectively, act on the noradrenergic systems. The noradrenergic action plays an important clinical effect in different antidepressant classes, as confirmed by the efficacy of dual action antidepressants such as the serotonin noradrenaline reuptake inhibitors (SNRIs), the noradrenergic and dopaminergic reuptake inhibitor (NDRI) Bupropion, and other compounds (e.g., Mianserin, Mirtazapine), which enhance the noradrenergic transmission. In addition, many tricyclics, such as Desipramine and Nortriptyline, have prevalent noradrenergic effect. Monoamine oxidase inhibitors (MAOIs), moreover, block the breakdown of serotonin, noradrenaline, dopamine and increase the availability of these monoamines. A novel class of antidepressants—the triple reuptake inhibitors—is under development to selectively act on serotonin, noradrenaline, and dopamine. Finally, the antidepressant effect of the atypical antipsychotic Quetiapine, indicated for the treatment of bipolar depression, is likely to be related to the noradrenergic action of its metabolite Norquetiapine. Even though a pure noradrenergic action might not be sufficient to obtain a full antidepressant effect, a pronoradrenergic action represents an important element for increasing the efficacy of mixed action antidepressants. In particular, the noradrenergic action seemed to be related to the motor activity, attention, and arousal.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives

BACKGROUNDnThe increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands scores.nnnMETHODSnMultivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands MCCB scores predicted REL neurocognitive performance.nnnRESULTSnSCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Probands scores significantly predicted REL MCCB scores on all domains except for visual learning.nnnCONCLUSIONSnIn a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Factors characterizing access and latency to first pharmacological treatment in Italian patients with schizophrenia, mood, and anxiety spectrum disorders

Latency to first pharmacological treatment [duration of untreated illness (DUI)] in psychiatric disorders can be measured in years, with differences across diagnostic areas and relevant consequences in terms of socio-occupational functioning and outcome. Within the psychopathological onset of a specific disorder, many factors influence access and latency to first pharmacotherapy and the present study aimed to investigate such factors, through an ad-hoc developed questionnaire, in a sample of 538 patients with diagnoses of schizophrenia-spectrum disorder (SZ), mood disorder (MD), and anxiety disorder (AD). Patients with SZs showed earlier ages at onset, first diagnosis and treatment, as well as shorter DUI compared with other patients (43.17 months vs. 58.64 and 80.43 months in MD and AD; F=3.813, P=0.02). Patients with MD and AD reported more frequently onset-related stressful events, benzodiazepines as first treatment, and autonomous help seeking compared with patients with SZs. In terms of first therapist, psychiatrist referral accounted for 43.6% of the cases, progressively decreasing from SZ to MD and AD (57.6, 41.8, and 38.3%, respectively). The opposite phenomenon was observed for nonpsychiatrist clinician referrals, whereas psychologist referrals remained constant. The present findings confirm the presence of a relevant DUI in a large sample of Italian patients with different psychiatric disorders (5 years, on average), pointing out specific differences, in terms of treatment access and latency, between psychotic and affective patients. Such aspects are relevant for detection of at-risk patients and implement early intervention programs.

The complex relationship between self-reported ‘personal recovery’ and clinical recovery in schizophrenia

Self-reported personal recovery and clinical recovery in schizophrenia (SRPR and CR, respectively) reflect different perspectives in schizophrenia outcome, not necessarily concordant with each other and usually representing the consumers or the therapists point of view. By means of a cluster analysis on SRPR-related variables, we identified three clusters. The first and third cluster included subjects with the best and the poorest clinical outcome respectively. The second cluster was characterized by better insight, higher levels of depression and stigma, lowest self-esteem and personal strength, and highest emotional coping. The first cluster showed positive features of recovery, while the third cluster showed negative features. The second cluster, with the most positive insight, showed a more complex pattern, a somewhat paradoxical mixture of positive and negative personal and clinical features of recovery. The present results suggest the need for a characterization of persons with schizophrenia along SRPR and CR dimensions to design individualized and integrated treatment programs aimed to improve insight and coping strategies, reduce stigma, and shape recovery styles.

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.

P-597 - Determination of psychopatological onset and latency to treatment in psychiatric disorders through the “psychopatological onset and latency to treatment questionnaire”

Introduction Few questionnaires on the psychopathological onset and latency to treatment in psychiatric patients are currently available. Objectives In this perspective we developed a brief questionnaire: the Psychopathological Onset Latency and Treatment Questionnaire (POLQ). Methods The questionnaire was administered to 265 patients with any psychiatric diagnosis. Statistical analyses were performed using SPSS. Results The sample showed the following demographic variables in terms of age (48xa0±xa015 years), occupation (17% unemployed) and familiarity (54%). Clinical variables included: age at onset (30.66xa0±xa015 years), age at first diagnosis (36xa0±xa019 years) and age at first drug treatment (35xa0±xa014 years). The most common symptoms at onset were related to the anxiety spectrum (41.2%), mood spectrum (24.5%) or both (25.3%). Stressful life-events in relation to onset occurred in 63% of patients (12.1% familiar issues, 11.3% work problems, bereavement or end of a relationship in 16.6%). Most frequent first diagnoses were major depressive episode (26.8%), manic/hypomanic/mixed episode (13.6%) and anxiety disorders (11.7%). Average latency to the first visit was 34 months. In the 76.2% of the sample, the first contact was with a psychiatrist, a psychologist in 15.8%; 78.1% were treated with drugs as a first treatment, 11.7% with psychotherapy, 7.2% with both. The average duration of first treatment was 23 months (4 weeks - 360 months) and reasons for discontinuation were: lack of efficacy (23.8%) or complete remission (21.9%). Conclusions POLQ resulted to be a useful and reliable instrument in the collection of information on the psychopatological onset and latency to treatment.

Disorganization and real-world functioning in schizophrenia: Results from the multicenter study of the Italian Network for Research on Psychoses

BACKGROUNDnA general consensus has not yet been reached regarding the role of disorganization symptoms in real-world functioning in schizophrenia.nnnMETHODSnWe used structural equations modeling (SEM) to analyze the direct and indirect associations between disorganization and real-world functioning assessed through the Specific Levels of Functioning Scale (SLOF) in 880 subjects with schizophrenia.nnnRESULTSnWe found that: 1) conceptual disorganization was directly and strongly connected with SLOF daily activities; difficulty in abstract thinking was associated with moderate strength to all SLOF domains, and poor attention was connected with SLOF work skills; 2) grandiosity was only related with poor work skills, and delusions were associated with poor functioning in all SLOF domains; interpersonal relationships were weakly indirectly influenced by hallucinatory behavior, delusions and unusual thought contents through the mediation of social cognition (SC); 3) among the negative symptoms, avolition had only direct links with SLOF work skills and SLOF activities; anhedonia had direct links with SLOF work skills and SLOF interpersonal and indirect link with SLOF work skills through functional capacity (FC); asociality with SLOF interpersonal; blunted affect had direct links with SLOF activities and indirect links with SLOF interpersonal relationships mediated by SC. Lastly, alogia had only indirect links mediated by SC, FC, and neurocognition (NC).nnnCONCLUSIONSnOverall conceptual disorganization is the symptom that contributed more (both directly and indirectly) to the activities of community living in real-world. Thus, it should be considered as a treatment target in intervention programs for patients with schizophrenia.

Ten-year outcome of vagus nerve stimulation-implanted patients with treatment-resistant depression: Two italian cases

Over the last 15 years, vagus nerve stimulation (VNS) has been used as an augmentative therapeutic intervention in patients with treatment-resistant depression (TRD), whether with a lifetime diagnosis of major depressive disorder or bipolar disorder. From being a potentially effective treatment in the acute phase of TRD, recently published treatment guidelines seemed to converge on the indication that VNS’s greatest benefit may be seen mostly beyond the short term. However, with the exception of a recent multicenter American report, very few studies have assessed the long-term efficacy of VNS in TRD patients. Herein, we present the cases of two Italian patients with TRD, with 10-year VNS follow-up evaluation. Both patients were found to benefit from augmentative VNS, and the latency of their stimulation response, tolerability, associated pharmacological treatment, number and duration of recurrences, and overall level of functioning are described and discussed. Further reports with larger samples are needed to support the long-term efficacy and tolerability of VNS in TRD patients, particularly beyond 5 years of follow-up.

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition

The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment.