Language production impairments in patients with a first episode of psychosis.

Language production has often been described as impaired in psychiatric diseases such as in psychosis. Nevertheless, little is known about the characteristics of linguistic difficulties and their relation with other cognitive domains in patients with a first episode of psychosis (FEP), either affective or non-affective. To deepen our comprehension of linguistic profile in FEP, 133 patients with FEP (95 non-affective, FEP-NA; 38 affective, FEP-A) and 133 healthy controls (HC) were assessed with a narrative discourse task. Speech samples were systematically analyzed with a well-established multilevel procedure investigating both micro- (lexicon, morphology, syntax) and macro-linguistic (discourse coherence, pragmatics) levels of linguistic processing. Executive functioning and IQ were also evaluated. Both linguistic and neuropsychological measures were secondarily implemented with a machine learning approach in order to explore their predictive accuracy in classifying participants as FEP or HC. Compared to HC, FEP patients showed language production difficulty at both micro- and macro-linguistic levels. As for the former, FEP produced shorter and simpler sentences and fewer words per minute, along with a reduced number of lexical fillers, compared to HC. At the macro-linguistic level, FEP performance was impaired in local coherence, which was paired with a higher percentage of utterances with semantic errors. Linguistic measures were not correlated with any neuropsychological variables. No significant differences emerged between FEP-NA and FEP-A (p≥0.02, after Bonferroni correction). Machine learning analysis showed an accuracy of group prediction of 76.36% using language features only, with semantic variables being the most impactful. Such a percentage was enhanced when paired with clinical and neuropsychological variables. Results confirm the presence of language production deficits already at the first episode of the illness, being such impairment not related to other cognitive domains. The high accuracy obtained by the linguistic set of features in classifying groups support the use of machine learning methods in neuroscience investigations.

Survey on centres and procedures for the diagnosis and treatment of adult ADHD in public services in Italy.

Attention deficit/hyperactivity disorder (ADHD) often persists into adulthood. Although its persistence and relative high prevalence, ADHD in adults is often underdiagnosed and undertreated in Italy, leading to poor clinical and functional outcomes, and higher costs of illness. The aims of the study were to identify the Italian mental health services for ADHD in adults, describe the diagnostic and treatment procedures they follow, and compare this offer with the recommendations of the German and English guidelines. The centres, that adopt a clinical and assessment protocol for adult ADHD diagnosis (carried out by specifically trained personnel) and prescribe pharmacological treatment for adult ADHD, were selected from the list of accredited services provided by the Appendix B.2 of the ISTISAN 16/37 Reports of the ISS. An ad-hoc survey including open-ended and close-ended questions was sent to each selected centre in February 2020. The overall picture resulting from the data analysis was compared with the recommendations of the German and English guidelines. The present survey shows that only a few centres are specialised in the diagnosis and treatment of ADHD in adults in Italy. Furthermore, there are no national guidelines for adult ADHD in Italy. The collected data also suggest that there is no a unified practice shared by the Centres both for the patient's transition from child and adolescent to adult mental health services and for the diagnostic-therapeutic process. It is therefore crucial to create specific protocols and develop national guidelines to better identify and diagnose ADHD in adults and provide targeted and more efficient multimodal treatments.

Dietary habits and physical activity in first-episode psychosis patients treated in community services. Effect on early anthropometric and cardio-metabolic alterations.

People with psychosis often develop metabolic and cardiovascular disorders, due to several factors including unhealthy lifestyle and antipsychotic treatment. This study aims to evaluate in a sample of first episode psychosis (FEP) patients lifestyle factors, with a specific emphasis on dietary habits and physical activity, and cardio-metabolic and anthropometric profile at illness onset and at 9 months. Moreover, this study aims to evaluate the impact of lifestyle factors on short term changes in cardio-metabolic and anthropometric profile. A 9-month follow-up study was conducted on a sample of 96 FEP patients recruited within the context of the GET UP program. Standardised assessments of dietary habits (EPIC) and physical activity (IPAQ) were retrospectively performed at 9 months; cardiovascular measures (blood pressure, heart rate), metabolic parameters (glucose, cholesterol, triglycerides), BMI and antipsychotic treatment were assessed at illness onset and at 9 months. We found that most FEP patients (60%) displayed poor dietary habits, as defined in terms of adherence to the Mediterranean diet. A significant increase for both BMI and cholesterol levels was found in the overall sample over 9 months. However, when considering the effect of lifestyle factors, BMI and total cholesterol were specifically raised in patients with low adherence to Mediterranean diet. The association with antipsychotic medication was found for SGA only, with a significant increase in both BMI and total cholesterol overtime. Our findings confirm the need to implement specific and early strategies to promote healthy lifestyle in people with FEP, since metabolic alterations occur within the first months of treatment.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial.

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size. METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome. RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected. CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

Positive symptoms in first-episode psychosis patients experiencing low maternal care and stressful life events: a pilot study to explore the role of the COMT gene.

COMT Val(158)Met moderates the effect of stress on psychotic symptoms. Exposure to stress is also associated with mesolimbic dopamine release in individuals experiencing low maternal care. We therefore test the hypothesis that recent stressful life events are associated with more severe positive symptoms (associated with mesolimbic dopamine release) in first-episode psychosis (FEP) patients who experienced low maternal care during childhood. We hypothesized that COMT Val(158)Met moderates this association. A total of 149 FEP patients recruited within the Psychosis Incident Cohort Outcome Study (PICOS) participated in the present study. Maternal care was assessed by the Parental Bonding Instrument (PBI), stressful life events were collected by the List of Events Scale and positive symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). We found that low maternal care and recent stressful life events were associated with higher level of positive symptoms at the onset (analysis of variance [ANOVA], p = 0.012), and that patients who were also homozygotes for the COMT Val(158) allele had the highest level of positive symptoms (ANOVA, p = 0.024). Low maternal care and severe stressful life events may contribute to a symptomatology characterized by more severe positive symptoms at the onset, possibly due to an increased mesolimbic dopamine release. Homozygosity for the COMT Val(158) allele seems to confer a biological predisposition to the stress-related hyperactivity of the mesolimbic dopaminergic system. The data imply that the mesolimbic dopaminergic system is involved in the mediation/modulation of the effect of stressful events on the vulnerability for psychosis.

First-contact incidence of psychosis in north-eastern Italy: influence of age, gender, immigration and socioeconomic deprivation.

BACKGROUND: Considerable variations in the incidence of psychosis have been observed across countries, in terms of age, gender, immigration status, urbanicity and socioeconomic deprivation. AIMS: To evaluate the incidence rate of first-episode psychosis in a large area of north-eastern Italy and the distribution of the above-mentioned risk factors in individuals with psychoses. METHOD: Epidemiologically based survey. Over a 3-year period individuals with psychosis on first contact with services were identified and diagnosed according to ICD-10 criteria. RESULTS: In total, 558 individuals with first-episode psychosis were identified during 3,077,555 person-years at risk. The annual incidence rate per 100,000 was 18.1 for all psychoses, 14.3 for non-affective psychoses and 3.8 for affective psychoses. The rate for all psychoses was higher in young people aged 20-29 (incidence rate ratio (IRR) = 4.18, 95% CI 2.77-6.30), immigrants (IRR = 2.26, 95% CI 1.85-2.75) and those living in the most deprived areas (IRR = 2.09, 95% CI 1.54-2.85). CONCLUSIONS: The incidence rate in our study area was lower than that found in other European and North American studies and provides new insights into the factors that may increase and/or decrease risk for developing psychosis.

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550.

The impact of cannabis use on age of onset and clinical characteristics in first-episode psychotic patients. Data from the Psychosis Incident Cohort Outcome Study (PICOS).

Cannabis use is frequent among first-episode psychosis (FEP) patients and has been associated with several clinical features. This study aimed in an FEP sample to determine whether cannabis use is associated with (1) a higher level of positive symptoms, a lower level of depression and a better premorbid adjustment, (2) an earlier age of onset, and a better premorbid IQ. The study was conducted within the framework of the Psychosis Incident Cohort Outcome Study (PICOS), a multisite collaborative research on FEP patients who attended the psychiatric services in Veneto Region, Italy. Standardized instruments were used to collect sociodemographic, clinical, and drug use data. A total of 555 FEP patients met the inclusion criteria, 517 of whom received an ICD-10 diagnosis of psychosis; 397 (55% males; mean age: 32 yrs ± 9.5) were assessed. Out of these, 311 patients agreed to be interviewed on drug and alcohol misuse; 20.3% was positive for drug misuse: cannabis (19.0%), cocaine (3.9%), and hallucinogens (3.9%). Cannabis use was not associated with a higher level of positive symptoms, but correlated with less severe depressive symptoms. No relationship was observed between premorbid adjustment or IQ and cannabis use. FEP patients who used cannabis had an earlier age of onset than abstinent patients, even after adjusting for gender and diagnosis. Our results suggest a possible causal role of cannabis in triggering psychosis in certain vulnerable subjects. Particular attention must be paid to this behaviour, because reducing cannabis use can delay or prevent some cases of psychosis.

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia.

BACKGROUND: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. METHODS/DESIGN: The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. DISCUSSION: The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.