Factors associated with lifetime suicide attempts in bipolar disorder: results from an Italian nationwide study.

The purpose of the present study was to detect demographic and clinical factors associated with lifetime suicide attempts in Bipolar Disorder (BD). A total of 1673 bipolar patients from different psychiatric departments were compared according to the lifetime presence of suicide attempts on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (presence of suicide attempts) at the univariate analyses, preliminary multiple logistic regression analyses were realized. A final multivariable logistic regression was then performed, considering the presence of lifetime suicide attempts as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. The final multivariable logistic regression analysis showed that an earlier age at first contact with psychiatric services (odds ratio [OR] = 0.97, p < 0.01), the presence of psychotic symptoms (OR = 1.56, p < 0.01) or hospitalizations (OR = 1.73, p < 0.01) in the last year, the attribution of symptoms to a psychiatric disorder (no versus yes: OR = 0.71, partly versus yes OR = 0.60, p < 0.01), and the administration of psychoeducation in the last year (OR = 1.49, p < 0.01) were all factors associated with lifetime suicide attempts in patients affected by BD. In addition, female patients resulted to have an increased association with life-long suicidal behavior compared to males (OR: 1.02, p < 0.01). Several clinical factors showed complex associations with lifetime suicide attempts in bipolar patients. These patients, therefore, require strict clinical monitoring for their predisposition to a less symptom stabilization. Future research will have to investigate the best management strategies to improve the prognosis of bipolar subjects presenting suicidal behavior.

Which factors delay treatment in bipolar disorder? A nationwide study focussed on duration of untreated illness.

AIM: The aim of the present study was to detect factors associated with duration of untreated illness (DUI) in bipolar disorder (BD). METHOD: A total of 1575 patients were selected for the purposes of the study. Correlation analyses were performed to analyse the relation between DUI and quantitative variables. The length of DUI was compared between groups defined by qualitative variables through one-way analyses of variance or Kruskal-Wallis's tests according to the distribution of the variable. Linear multivariable regressions were used to find the most parsimonious set of variables independently associated with DUI: to this aim, qualitative variables were inserted with the numeric code of their classes by assuming a proportional effect moving from one class to another. RESULTS: An inverse significant correlation between length of DUI and time between visits in euthymic patients was observed (r = -.52, P < .001). DUI resulted to be longer in patients with: at least one lifetime marriage/partnership (P = .009), a first psychiatric diagnosis of major depressive disorder or substance abuse (P < .001), a depressive polarity of first episode (P < .001), no lifetime psychotic symptoms (P < .001), BD type 2 (P < .001), more lifetime depressive/hypomanic episodes (P < .001), less lifetime manic episodes (P < .001), presence of suicide attempts (P = .004), depressive episodes (P < .001), hypomanic episodes (P = .004), hospitalizations (P = .011) in the last year. CONCLUSIONS: Different factors resulted to increase the length of DUI in a nationwide sample of bipolar patients. In addition, the DUI was found to show a negative long-term effect in terms of more suicidal behaviour, more probability of hospitalization and depressive/hypomanic episodes.

Adult ADHD: Prevalence and Clinical Correlates in a Sample of Italian Psychiatric Outpatients.

Objective: ADHD remains a largely underdiagnosed disorder in Europe and especially in Italy. Aims of the present study were to assess the prevalence of ADHD and its clinical and demographic correlates in a large sample of Italian outpatients. Method: 634 outpatients accessing psychiatric services were assessed with the Mini-International Neuropsychiatric Interview (MINI) Plus V. 5.0.0 interview and the Adult ADHD self-report Scale Symptoms Checklist (ASRS)-V 1.1 Short Form. Patients positive to the ASRS-V 1.1 were assessed with the Diagnostic Interview for ADHD in Adults (DIVA) 2.0. Results: Of the total patients' sample, 81 (12.8%) were positive on the ASRS-V 1.1. After performing the DIVA 2.0, 44 patients (6.9%) met the criteria for Adult ADHD. Significant clinical and demographic differences between ADHD positive and negative groups were found. Conclusion: The prevalence and correlates of ADHD comorbidity in our outpatient psychiatric population were comparable to those found in other high-income countries. Considering the prevalence of ADHD and its impact on functioning, implementing specific knowledge on this subject is needed.

Change in core symptoms of borderline personality disorder by tDCS: A pilot study.

Borderline personality disorder (BPD) recognizes several psychopathological dimensions related to prefrontal cortex impairments. Transcranial Direct Current Stimulation (tDCS) targeting the right prefrontal dorsolateral cortex (DLPFC) positively influence cognitive functions related to impulsivity in healthy subjects. A randomized double-blind study was designed to investigate whether tDCS could modulate core dimensions (impulsivity, aggression, affective dysregulation) of BPD. Also effects on decision making process and substances craving was assessed. Patients were randomized to receive active-tDCS at 2 mA versus sham-tDCS, once a day for 15 sessions. Anode was placed on the right DLPFC (F4), cathode on the left DLPFC (F3). Impulsivity and aggression measures were significantly reduced only in patients treated with active-tDCS. Decision-making process was marginally influenced by the active current. Craving intensity was reduced only in the active-tDCS sample. Both groups showed improvements in the affective dysregulation dimension and anxious and depressive symptoms. The application of bilateral tDCS targeting right DLPFC with anodal stimulation seems to improve core dimensions of BPD (mainly impulsivity and aggression) probably by restoring prefrontal activity. tDCS might be a potential tool for preventing self-harming behaviors.

Association study between HTR2A rs6313 polymorphism and early response to risperidone and olanzapine in schizophrenia patients.

Antipsychotic drugs are the preferred choice for schizophrenia treatment; however, response is highly variable. In the context of the search for predictors of antipsychotic treatment effectiveness, the evaluation of response within 2 weeks has been indicated to predict long-term outcome. Moreover, a focus on symptomatological domains could be helpful to better characterize antipsychotic response, identifying more specific predictors. Pharmacogenetic studies have indicated a role for rs6313 in the serotonin receptor gene HTR2A in affecting response to antipsychotics, with heterogeneous results. With the aim to test for the first time the application of a dimensional approach for the evaluation of early response, we carried out a genetic association study between rs6313 and antipsychotic response in two groups of schizophrenia patients in monotherapy with risperidone (n = 121) and olanzapine (n = 100). Patients were evaluated at the baseline and after 1 and 2 weeks of treatment. When comparing early responders versus early nonresponders, no association was detected for the two drugs separately, whereas by taking into consideration the two drugs together it was observed that carriers of the T allele had a higher response probability compared to noncarriers. Considering 2-week improvements, changes in PANSS total scores, subscores and in PANSS Emsley's symptomatological dimensions were associated with rs6313 for both risperidone and olanzapine. Moreover, the repeated measures analysis indicated an association of rs6313 with the disorganized thought dimension for risperidone, and with the depressive and anxiety dimensions for olanzapine. These data add support to the hypothesis that the HTR2A gene is involved in antipsychotic treatment outcome.

Post-traumatic stress disorder and subthreshold post-traumatic stress disorder in recent male asylum seekers: An expected but overlooked "European" epidemic.

The literature shows an increased risk for post-traumatic stress disorder (PTSD) among illegal migrants. We aimed to estimate the prevalence of PTSD, subthreshold PTSD, the degree of disability, and differences in sociodemographic and anamnestic characteristics associated with these clinical conditions in a sample of newly arrived migrants. Two hundred male asylum seekers from West sub-Saharan Africa were evaluated for traumatic life events, PTSD symptoms, and disability through the Life Events Checklist for DSM-5 (LEC-5), the Primary Care PTSD Screen, the PTSD Checklist for DSM-5, and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). The current prevalence of PTSD and subthreshold PTSD was 9.5% and 12.0%, respectively. PTSD and subthreshold PTSD subgroups presented higher WHODAS 2.0 scores and LEC-5 events, an over-representation of individuals with childhood adversities and an excess of premigration psychiatric contacts unrelated to PTSD spectrum disorders and peri-migration offences. Witnessing a traumatic event and disability in understanding and communication predicted both the presence of PTSD symptoms and PTSD status. PTSD spectrum disorders should be considered among the clinical emergencies associated with asylum seeker condition, and targeted interventions also involving the host citizens should be predisposed.

Paliperidone extended-release in the short- and long-term treatment of schizophrenia.

Paliperidone is a second-generation antipsychotic drug belonging to the class of benzisoxasole derivatives. Paliperidone is the major active metabolite of risperidone (9-OH-risperidone) and, as such, is comparable to the latter in terms of pharmacodynamic properties. However, due to its peculiar characteristics, paliperidone may be particularly useful in the treatment of schizophrenic patients. In this critical review of the literature the efficacy and tolerability in the short- and in the long-term have been evaluated in patients with schizophrenia. Taking into account the tolerability and efficacy data, together with the use of innovative sustained-release formulation, with a peculiar pharmacokinetic profile that allows single daily administration, paliperidone can be considered a valid option both for the short and the long-term treatment of schizophrenia.

Well-being in patients with schizophrenia, mood and personality disorders attending psychiatric services in the community. A controlled study.

BACKGROUND: Poor attention is paid by recent research to the prevalence of mental well-being in psychiatric patients and the comparison between groups with different diagnoses. Data suggest that the presence of mental illness does not necessarily mean the absence of well-being, particularly in stable outpatients. METHODS: A consecutive series of 375 patients attending two community mental health centers was given the Mental Health Continuum Short Form (MHC-SF) and the Clinical Global Impression - Severity scale. Diagnoses were made after the MINI Neuropsychiatric Interview and a chart review of all relevant clinical information. The flourishing category and the three components of MHC-SF were used to rate well-being. A total of 274 controls were taken from the employees at a local firm. RESULTS: The rates of flourishing mental health were: 33.1% schizophrenia, 36.6% bipolar disorder, 23.3% unipolar depression, 24.4% cluster B personality disorder, and 53.3% controls (p < 0.001). The comparison of the three MHC components across diagnostic groups found that unipolar depression and cluster B personality patients had significantly lower scores compared to bipolar and schizophrenia patients. Flourishing mental health was detected more often in males than females (34.9% vs. 24.1% - p < 0.05). For schizophrenia patients indices of well-being were better in those on depot medications. CONCLUSIONS: Psychiatric outpatients with major mental illness have lower rates of well-being compared to controls, although about one-third is flourishing. Patients with unipolar depression and cluster B personality disorder may deserve special attention when planning intervention for fostering well-being.

Assessment of de novo copy-number variations in Italian patients with schizophrenia: Detection of putative mutations involving regulatory enhancer elements.

OBJECTIVES: Variants appearing de novo in genes regulating key neurodevelopmental processes and/or in non-coding cis-regulatory elements (CREs), as enhancers, may increase the risk for schizophrenia. However, CREs involvement in schizophrenia needs to be explored more deeply. METHODS: We investigated de novo copy-number variations (CNVs) in the whole-genomic DNA obtained from 46 family trios of schizophrenia probands by using the Enhancer Chip, a customised array CGH able to investigate the whole genome with a 300-kb resolution, specific disease loci at a ten-fold higher resolution, and which was highly enriched in probes in more than 1,250 enhancer elements selected from Vista Enhancer Browser. RESULTS: In seven patients, we found de novo CNVs, two of which overlapped VISTA enhancer elements. De novo CNVs encompass genes (CNTNAP2, MAGI1, TSPAN7 and MET) involved in brain development, while that involving the enhancer element hs1043, also includes ZIC1, which plays a role in neural development and is responsible of behavioural abnormalities in Zic mutant mice. CONCLUSIONS: These findings provide further evidence for the involvement of de novo CNVs in the pathogenesis of schizophrenia and suggest that CNVs affecting regulatory enhancer elements could contribute to the genetic vulnerability to the disorder.

Paliperidone palmitate in short- and long-term treatment of schizophrenia.

Poor adherence to treatment remains a major problem in the management of patients with schizophrenia. In the 60s, first generation antipsychotics in depot formulation have been introduced on the market with the aim to improve adherence to therapy. However, the limited effectiveness on negative symptoms and the tendency to induce extrapyramidal side effects has limited their use. Currently there are five second-generation antipsychotic long-acting formulations and the use of these drugs has definitely changed perspective: they are no more restricted as compounds intended to improve compliance, but they can be considered first-line drugs with proven efficacy and good tolerability. In this narrative review the efficacy and tolerability of paliperidone palmitate, as well as the economic impact of the use of this particular molecule, have been evaluated in the short- and long-term treatment of schizophrenia. Taking into account the results of different studies, paliperidone, especially in his long-acting formulation, can be considered a viable and effective treatment for patients with schizophrenia, both in the short- and in the long term.

Psychomotor agitation in subjects hospitalized for an acute exacerbation of Schizophrenia.

The aims of this study were to establish the prevalence of moderate and severe psychomotor agitation in patients hospitalized for an active phase of schizophrenia, the associations between psychomotor agitation and patients' demographic and clinical variables, the intra-individual stability of the agitated/non-agitated dichotomy in independent psychotic breakdowns. The study was performed on a database relative to 630 inpatients hospitalized with a diagnosis of schizophrenia. Psychomotor agitation was measured with the Positive and Negative Syndrome Scale - Excited Component (PANSS-EC). Prevalence of moderate and severe psychomotor agitation was 40.5% and 23.7%, respectively. Non-agitated patients were older, with longer illness history and duration of untreated psychosis, were more frequently on antipsychotic medication, had lower incidence of recent use of substances, and functioned better before the index hospitalization than moderately and/or severely agitated patients. Non-agitated patients had lower scores for total PANSS and Emsley's positive and anxiety dimensions. Compared with the severely agitated group, non-agitated and moderately agitated patients scored more in Emsley's depression dimension. Poor functioning before index hospital admission, higher scores for negative subscale and Emsley's positive dimension and use of substances exerted an effect on risk of psychomotor agitation.

At-risk gambling in patients with severe mental illness: Prevalence and associated features.

Background and aims The primary objective of this study was to investigate the prevalence of at-risk gambling in a large, unselected sample of outpatients attending two community mental health centers, to estimate rates according to the main diagnosis, and to evaluate risk factors for gambling. Methods All patients attending the centers were evaluated with the Canadian Problem Gambling Index and the Mini International Neuropsychiatric Interview. Diagnoses were checked with the treating psychiatrists and after a chart review of the university hospital discharge diagnoses. Results The rate of at-risk gambling in 900 patients was 5.3%. In those who gambled over the last year, 10.1% were at-risk gamblers. The rates in the main diagnostic groups were: 4.7% schizophrenia and related disorders, 4.9% bipolar disorder, 5.6% unipolar depression, and 6.6% cluster B personality disorder. In 52.1% of the cases, at-risk gambling preceded the onset of a major psychiatric disorder. In a linear regression analysis, a family history of gambling disorder, psychiatric comorbidities, drug abuse/dependence, and tobacco smoking were significantly associated with at-risk gambling. Discussion and conclusion The results of this study evidenced a higher rate of at-risk gambling compared to community estimates and call for a careful screening for gambling in the general psychiatric population.

Socio-demographic and clinical characterization of patients with Bipolar Disorder I vs II: a Nationwide Italian Study.

Bipolar disorders (BDs) are prevalent, comorbid and disabling conditions, associated with the highest suicide risk among psychiatric illnesses. In the last few years, new efforts to better characterize the socio-demographic and clinical profiles of BD type I vs II have been documented by several reports, with novel and insightful findings in the field. The present multicenter study aimed to provide a comprehensive and reliable representation of the Italian reality, through the analysis of the largest national sample of bipolar patients collected so far. A total of 1500 patients (BD I n = 963 and BD II n = 537) from different psychiatric departments, participating in the Italian Chapter of the "International Society of Bipolar Disorders" (ISBD), were assessed and divided into two groups on the basis of their diagnostic subtype, and different socio-demographic and clinical variables were compared between the two subgroups. Chi-squared tests for categorical variables and t tests for continuous variables were performed for group comparison. Furthermore, a multivariable logistic regression was performed, considering diagnostic bipolar subtype (type I or II) as dependent variable, and socio-demographic/clinical characteristics as independent variables. BD I vs II patients showed an overall less favorable socio-demographic and clinical profile. In addition, the multivariable logistic regression showed that BD II vs BD I was predicted by the absence of lifetime suicide attempts (OR = 1.58, p = 0.01), a later age of diagnosis (OR = 1.03, p < 0.01), less hypomanic episodes in the last year (OR = 2.29, p < 0.0001) and absence of psycho-educational interventions in the last year (OR = 0.51, p < 0.01). BD I and II patients were found to significantly differ in relation to specific clinical variables, which should be considered within updated diagnostic-therapeutic algorithms.

Feasibility and effectiveness of cognitive remediation in the treatment of borderline personality disorder.

Several studies have demonstrated that borderline personality disorder (BPD) is associated with neuropsychological deficits and there is evidence that the neurocognitive profile of patients with BPD may be related to the outcome of this disorder. The aim of this study was to investigate the feasibility and the effectiveness of a cognitive remediation intervention in patients with BPD. Thirty patients with a DSM-IV-TR diagnosis of BPD were assessed on clinical, neuropsychological and functional outcome measures at baseline and after 16 weeks of a computer-assisted cognitive remediation (CACR) intervention or treatment as usual (TAU). Patients who received CACR showed a greater improvement in working memory and psychosocial functioning measures than patients treated with TAU. Symptom severity was not significantly affected by CACR treatment. The findings of this pilot study suggest the feasibility and potential effectiveness on specific cognitive domains, but modest clinical usefulness of a computerised modality of cognitive remediation in the treatment of BPD.

Exome sequencing in schizophrenic patients with high levels of homozygosity identifies novel and extremely rare mutations in the GABA/glutamatergic pathways.

Inbreeding is a known risk factor for recessive Mendelian diseases and previous studies have suggested that it could also play a role in complex disorders, such as psychiatric diseases. Recent inbreeding results in the presence of long runs of homozygosity (ROHs) along the genome, which are also defined as autozygosity regions. Genetic variants in these regions have two alleles that are identical by descent, thus increasing the odds of bearing rare recessive deleterious mutations due to a homozygous state. A recent study showed a suggestive enrichment of long ROHs in schizophrenic patients, suggesting that recent inbreeding could play a role in the disease. To better understand the impact of autozygosity on schizophrenia risk, we selected, from a cohort of 180 Italian patients, seven subjects with extremely high numbers of large ROHs that were likely due to recent inbreeding and characterized the mutational landscape within their ROHs using Whole Exome Sequencing and, gene set enrichment analysis. We identified a significant overlap (17%; empirical p-value = 0.0171) between genes inside ROHs affected by low frequency functional homozygous variants (107 genes) and the group of most promising candidate genes mutated in schizophrenia. Moreover, in four patients, we identified novel and extremely rare damaging mutations in the genes involved in neurodevelopment (MEGF8) and in GABA/glutamatergic synaptic transmission (GAD1, FMN1, ANO2). These results provide insights into the contribution of rare recessive mutations and inbreeding as risk factors for schizophrenia. ROHs that are likely due to recent inbreeding harbor a combination of predisposing low-frequency variants and extremely rare variants that have a high impact on pivotal biological pathways implicated in the disease. In addition, this study confirms that focusing on patients with high levels of homozygosity could be a useful prioritization strategy for discovering new high-impact mutations in genetically complex disorders.

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.

The Role of Metabotropic Glutamate Receptor Genes in Schizophrenia.

Genomic studies revealed two main components in the genetic architecture of schizophrenia, one constituted by common variants determining a distributed polygenic effect and one represented by a large number of heterogeneous rare and highly disruptive mutations. These gene modifications often affect neural transmission and different studies proved an involvement of metabotropic glutamate receptors in schizophrenia phenotype. Through the combination of literature information with genomic data from public repositories, we analyzed the current knowledge on the involvement of genetic variations of the human metabotropic glutamate receptors in schizophrenia and related endophenotypes. Despite the analysis did not reveal a definitive connection, different suggestive associations have been identified and in particular a relevant role has emerged for GRM3 in affecting specific schizophrenia endophenotypes. This supports the hypothesis that these receptors are directly involved in schizophrenia disorder.

Does cognitive remediation modify the use of psychiatric services and the patterns of care of patients with schizophrenia?

The use of inpatient and outpatient psychiatric services were assessed in the 12months before and after a cognitive remediation (CR) intervention or treatment as usual (TAU) in a sample of 84 patients with schizophrenia who previously underwent an effectiveness study of CR. A smaller number and shorter duration of hospitalizations in acute wards and a higher total number of outpatient and rehabilitative interventions, as well as a more constant, intensive and articulated rehabilitation in the 12months after the intervention were found in patients who received CR, compared with those who received TAU. CR may modify the use of psychiatric services and the patterns of care of patients with schizophrenia.