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.

Obstetric complications and subsequent risk of mood disorders for offspring in adulthood: a comprehensive overview.

Background: A number of studies reported obstetric complications (OCs) to be a risk factor for the development of psychiatric conditions in the adulthood, including mood disorders.Aim: The aim of this study was to review the literature about the link between OCs during the perinatal period (items of Lewis-Murray scale) and the future risk of developing a mood disorder in adulthood, such as the major depressive disorder (MDD) or the bipolar disorder (BD).Methods: A research in the main database sources has been conducted to obtain an overview of the association mentioned above.Results: Few studies have investigated the role of OCs in the development of mood disorders in adulthood. The most robust evidence is that low birth weight (LBW) and preterm birth may be risk factors for the development of MDD in the future, even if some of the available data come from studies with small sample sizes or a retrospective design.Conclusion: OCs may confer a risk of developing mood disorders in adulthood. Future research should confirm these preliminary findings and clarify if other obstetric or neonatal complications (e.g. cyanosis or newborn epileptic seizures) may have a role in the future onset of mood disorders.

A miRNome analysis of drug-free manic psychotic bipolar patients versus healthy controls.

The lifetime presence of psychotic symptoms is associated with more clinical severity, poorer outcome and biological changes in patients affected by bipolar disorder (BD). Epigenetic mechanisms have been evoked to explain the onset of psychotic symptoms in BD as well as the associated biological changes. The main objective of the present study was to evaluate the expression profiles of circulating microRNAs (miRNAs) in drug-free manic psychotic bipolar patients versus healthy controls (HC), to identify possible non-invasive molecular markers of the disorder. 15 drug-free manic psychotic bipolar patients and 9 HC were enrolled and 800 miRNAs expression profile was measured by Nanostring nCounter technology on plasma samples and validated through qPCR. Overall, twelve miRNAs showed a significantly altered expression between the two groups (p < 0.05). Functional annotation of predicted miRNAs targets by MultiMIR R tool showed repression in bipolar patients of genes with a role in neurodevelopment and neurogenesis, and upregulation of genes involved in metabolism regulation. We identified a signature of circulating miRNA characteristic of manic psychotic bipolar patients, suggesting a possible role in neurodevelopment and metabolic processes regulation.

Differential core pharmacotherapy in bipolar I versus bipolar II disorder and European versus American patients not in a syndromal episode.

Assess bipolar disorder subtype and treatment location effects on bipolar disorder core pharmacotherapy. Outpatients not in a syndromal episode referred to the University of Milan and Stanford University Bipolar Disorder Clinics were assessed with SCID for the fourth Edition of the Diagnostic and Statistical Manual of Mood Disorders, and the Systematic Treatment Enhancement Program for Bipolar Disorder Affective Disorders Evaluation, respectively. Prevalence and clinical correlates of antidepressant, antipsychotic, and mood stabilizer use, in aggregate and individually, were compared in bipolar I (BDI) versus II (BDII) patients in Milan/Stanford and in Milan versus Stanford patients, stratified by subtype. Milan/Stanford pooled BDI versus BDII patients significantly more often took antipsychotic (69.8 versus 44.8%), mood stabilizers (68.6 versus 57.7%), and valproate (40.1 versus 17.5%), and less often took antidepressants (23.1 versus 55.6%) and lamotrigine (9.9 versus 25.2%). Milan versus Stanford patients (stratified by bipolar disorder subtype) significantly more often took antipsychotic (BDI and BDII), antidepressants (BDII), and valproate (BDII), and less often took lamotrigine (BDI). Research regarding bipolar disorder core pharmacotherapy relationships with bipolar subtype and treatment location is warranted to enhance clinical management.

Correlates of current rapid-cycling bipolar disorder: Results from the Italian multicentric RENDiBi study.

BACKGROUND: we aimed to compare socio-demographic and clinical differences between patients with versus without current RC in order to detect clinical factors that may favor early diagnosis and personalized treatment. METHODS: A total of 1675 patients (males: n = 714 and females: n = 961; bipolar 1: n = 1042 and bipolar 2: n = 633) from different psychiatric clinics were grouped and compared according to the current presence of RC in terms of socio-demographic and clinical variables. Chi-squared tests for qualitative variables and Student's t tests for quantitative variables were executed for group comparison, and multivariable logistic regressions were performed, considering the current presence of RC as dependent variable, and socio-demographic/clinical factors as independent variables. RESULTS: Female gender (male versus female: OR = 0.64, p = 0.04), unidentifiable prevalent polarity (versus depressive polarity: OR = 1.76, p = 0.02; versus manic polarity: OR: 2.86, p < 0.01) and hospitalization in the last year (no versus yes: OR = 0.63, p = 0.02) were found to be associated with RC in the final multivariable regression analysis. CONCLUSIONS: RC in BD seems to be more prevalent in female gender and associated with some unfavorable clinical features, such as an increased risk of hospitalization. These aspects should be taken into account in the management and monitoring of RC versus non-RC patients.

Shared Obsessive-Compulsive Disorder: An Italian Case Report.

Shared obsessive-compulsive disorder (S-OCD) has seldom been reported in the literature, whereas shared psychotic disorder has been described since the end of 19th century. The aim of this report was to describe a case of S-OCD in a married couple. A 38-year-old OCD patient, after several pharmacological trials, eventually improved when a combination of escitalopram and risperidone was prescribed. During his symptoms' remission, his wife started developing the same OCD symptoms. She was prescribed escitalopram, but, given her inconsistent compliance, it was difficult to obtain full effectiveness of the pharmacological treatment. The case showed several common features with S-OCD. Obsessions and delusions could be considered as extremes of the same spectrum-an option recognized by the Diagnostic and statistical manual of mental disorders, fifth edition within the "OCD with poor insight" category-and S-OCD could represent the continuum between OCD and psychotic conditions. Additional investigation is required to better understand psychotic and nonpsychotic shared disorders.

Gender-related differences in patients with bipolar disorder: a nationwide study.

OBJECTIVE: The possible presence of gender-related differences in patients with bipolar disorder (BD) may have diagnostic and therapeutic implications. This multicenter study aimed to investigate gender differences in BD in the largest Italian database collected to date, on behalf of the Italian Chapter of the International Society of Bipolar Disorders. METHODS: A total of 1674 patients (males: n = 714; females: n = 960) from different psychiatric departments were compared according to gender on demographic/clinical variables. Owing to the large number of variables statistically related to the dependent variable (gender) at the univariate analyses, preliminary multiple logistic regression analyses were performed. A final multivariable logistic regression was then performed, considering gender as the dependent variable and statistically significant demographic/clinical characteristics as independent variables. RESULTS: The results of the final multivariable logistic regression analysis with previous statistically significant demographic and clinical variables were the following: female gender was less frequently associated with employment (odds ratio [OR] = 0.7, P < 0.01), lifetime single marital status (OR = 0.45, P < 0.01), and substance abuse in the last year (OR = 0.35, P < 0.01), whereas it was more frequently associated with a major number of lifetime major depressive episodes (OR = 1.78, P < 0.01) and psychiatric visits in the last year (OR = 1.38, P = 0.01). CONCLUSION: Few significant differences were found between genders in BD, particularly for those clinical features that are associated with poor prognosis (substance abuse for males and number of depressive episodes for females). Transcultural studies are needed to identify cultural versus illness-related variables possibly explaining the different clinical presentation of BD in relation to gender.

Is trazodone more effective than clomipramine in major depressed outpatients? A single-blind study with intravenous and oral administration.

OBJECTIVE: Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration). METHODS: Some 42 patients with a diagnosis of MDD according to the DSM-5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment. RESULTS: No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine. CONCLUSION: Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study [corrected].

Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = - 0.51, p = 0.04) and in male BD patients (r = - 0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Benzodiazepine ingestion as a way to die by suicide and related safety: the case of an elderly patient.

Benzodiazepines (BDZs) are widespread psychotropic compounds, often prescribed as first-line symptomatic option by general practitioners in patients with different psychiatric disorders. Sometimes, however, they contribute to delay the administration of the first appropriate psychopharmacological treatment, thus leading to a longer duration of untreated illness in patients with depressive and anxiety disorders. The well-established pros of BDZs use in clinical practice include efficacy, rapidity of action, versatility, and safety. Among the cons, BDZs can provoke cognitive side-effects, asthenia, and misuse/abuse. Although their overall safety has been traditionally viewed as one of their greatest strengths, BDZs massive ingestion for suicidal purposes may pose, in some cases, serious life-threatening conditions, as described in the present case report. Hence, particular attention needs to be paid in prescribing these compounds to special populations, such as elderly patients. Among these, their prescription should be limited to the short-term and particularly monitored in case of risk factors, as they may be unsafe in case of overdose.

Correlation of Health-Related Quality of Life in Clinically Stable Outpatients with Schizophrenia.

BACKGROUND: Generic health-related quality of life (HRQoL) scales are increasingly being used to assess the effects of new treatments in schizophrenia. The objective of this study is to better understand the usefulness of generic and condition specific HRQoL scales in schizophrenia by analyzing their correlates. METHODS: Data formed part of the Pattern study, an international observational study among 1379 outpatients with schizophrenia. Patients were evaluated with the Mini International Neuropsychiatric Inventory, the Clinical Global Impression-Schizophrenia (CGI-SCH) Scale and the Positive and Negative Syndrome Scale (PANSS) and reported their HRQoL using the Schizophrenia Quality of Life Scale (SQLS), the Short Form-36 (SF-36), and the EuroQol-5 Dimension (EQ-5D). The two summary values of the SF-36 (the Mental Component Score and the Physical Component Score, SF-36 MCS and SF-36 PCS) were calculated. RESULTS: Higher PANSS positive dimension ratings were associated with worse HRQoL for the SQLS, EQ-5D VAS, SF-36 MCS, and SF-36 PCS. Higher PANSS negative dimension ratings were associated with worse HRQoL for the EQ-5D VAS, SF-36 MCS, and SF-36 PCS, but not for the SQLS or the EQ-5D tariff. PANSS depression ratings were associated with lower HRQoL in all the scales. There was a high correlation between the HRQoL scales. However, in patients with more severe cognitive/disorganized PANSS symptoms, the SQLS score was relatively higher than the EQ-5D tariff and SF-36 PCS scores. CONCLUSION: This study has shown substantial agreement between three HRQoL scales, being either generic or condition specific. This supports the use of generic HRQoL measures in schizophrenia. CLINICALTRIALSGOV IDENTIFIER: NCT01634542 (July 6, 2012, retrospectively registered).

The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study.

BACKGROUND: Somatoform disorders (SDs) are a heterogeneous group of psychiatric syndromes characterized by common symptoms, which may mimic a physical condition but they are not explained by a medical condition. Although the biologic nature of this disorder has been widely accepted, the neuroanatomical correlates characterizing SDs are still inconclusive. OBJECTIVE: This study aims to explore gray matter (GM) volume alterations in SD patients compared to healthy controls and their possible association with clinical and cognitive measures. METHOD: We used voxel-based morphometry to examine regional GM volumes in 20 inpatients with SDs and 24-matched healthy controls. Only for SD patients, we employed multiple instruments to assess psychopathology and cognitive functioning, which were then used to explore their association with GM volume deficits. RESULTS: Compared to healthy controls, SD patients showed GM volume reductions in the hypothalamus, left fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected). Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating Scale scores negatively correlated with specific fronto-temporoparietal regions whereas Symptom Checklist-90-Sleep scores positively correlated with anterior cingulate cortex. Lastly, the Boston Naming Test negatively correlated with fronto-temporoparietal and striatal volumes whereas Free and Cued Selective Reminding Test and Stroop scores positively correlated with superior temporal gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error corrected). CONCLUSION: Our results suggest that SDs might be characterized by selective impairments in specific cortico-limbic regions associated to two overlapping circuits, the neuromatrix of pain and the emotion regulation system.

Correction to: Cingulate abnormalities in bipolar disorder relate to gender and outcome: a region-based morphometry study.

In the original publication of the article, the title was incorrect. The correct title should read as given below.

Efficacy of oral trazodone slow release following intravenous administration in depressed patients: a naturalistic study.

BACKGROUNDS: Up to date, no studies in literature assessed the efficacy of a treatment schedule including i.v. trazodone followed by its oral administration. In light of this lack of evidence, the aim of the present study was to evaluate the efficacy and tolerability of trazodone, administered first i.v. and then orally in a sample of Major Depressive Disorder (MDD) patients. METHODS: Thirty four patients underwent i.v. administration of trazodone (75-100 mg in 250 mL of saline) for 1 week. During the second week, oral extended-release formulation (150-300 mg per day) was added to the i.v. administration. Finally, extended-release trazodone was orally administration at doses of 150-300 mg per day. Psychometric scales were performed at baseline (T0), after 2 weeks (T1), 6 weeks (T2), after 3 months (T3), and 6 months (T4). RESULTS: The total sample included 34 subjects (14 males and 20 females). There was a statistically significant decrease in Hamilton Depression Rating Scale total scores from T0 to T1 (t=9.06; df=33), from T1 to T2 (t=4.96; df=29), from T2 to T3 (t=4.08; df=19), and from T3 to T4 (t=2.25; df=19); in Hamilton Anxiety Rating Scale total scores from T0 to T1 (t=8.79; df=33) and from T1 to T2 (t=5.61; df=29); in Montgomery-Asberg Depression Rating Scale total scores from T0 to T1 (t=9.30; df=33), from T1 to T2 (t=5.69; df=29), and from T2 to T3 (t=3.16; df=19). CONCLUSIONS: This finding confirms previous results on depression with concomitant anxiety symptoms: focusing on trazodone prolonged-release formulation, available data documented its efficacy in MDD.

The relationship of IQ and emotional processing with insula volume in schizophrenia.

OBJECTIVE: The insula is involved in general and social cognition, in particular emotion regulation. Aim of this study is to investigate whether insula volume is associated with Intelligence Quotient (IQ) and emotional processing in schizophrenia patients versus healthy controls (HC). METHODS: Magnetic resonance imaging (MRI) brain scans, IQ and emotional processing tests (Benton Facial Recognition Test [BFRT], Degraded Facial Affect Recognition Task [DFAR], Emotional Mentalizing Task [EMT]) were administered in 246 subjects (133 schizophrenia patients and 113 controls). First order linear regression analyses were performed with group as independent variable and IQ/emotional processing test scores as dependent variables. Second order stepwise linear regression analyses were performed with IQ/emotional processing test scores as independent variables (as well as intracranial volumes, age, gender and cannabis abuse) and right/left insula volumes as dependent ones. A final mediation analysis (Sobel test) was performed to verify if IQ or emotional processing test scores could explain the eventual differences in insula volumes between the two groups. RESULTS: Schizophrenia patients presented lower insula volumes (left: F = 9.72, p < 0.01; right: F = 10.93, p < 0.01) as compared with healthy controls. Smaller insula volumes in schizophrenia patients are mediated by lower IQ scores (Sobel tests: 3.07, p < 0.01 for right insula; 2.72, p < 0.01 for left insula), but not by impairments in emotion processing. CONCLUSIONS: IQ, but not emotional processing mediates smaller insula volumes in schizophrenia patients.

THE USE OF LONG-ACTING ANTIPSYCHOTICS FOR THE MANAGEMENT OF AGGRESSIVENESS IN SCHIZOPHRENIA: A CLINICAL OVERVIEW.

Aggressive behaviour represents a challenge in the treatment of patients with schizophrenia, being often associated with clinical predictors of severity of illness such as poor insight, psychotic re-exacerbation, concomitant substance misuse or comorbidity with personality disorders. As psychotic relapses and consequent risk of aggressive behaviour are often associated with a poor compliance, purpose of the present manuscript is to give an overview of the available data about the use of depot antipsychotics for the management of violence in patients with schizophrenia. A research in the main database sources has been conducted to identify relevant papers about the topic. Few studies (most of them retrospective and with small sample sizes) have investigated the effectiveness of depot antipsychotic for the treatment of aggressive behaviour in schizophrenia. Aripiprazole depot appears to be promising for the management of aggressive behaviour of subjects with schizophrenia, however data about its efficacy in the long-term are absent and lack of evidence prevents the recommendation of this compound for the treatment of aggressiveness in subjects affected by schizophrenia. In addition, there is not sufficient evidence to conclude that a specific depot antipsychotic may have a better efficacy on aggressive behaviour of patients affected by schizophrenia. Prospective comparative studies (e.g. with oral clozapine and aripiprazole depot) are needed to assess the real clinical advantage of the use of depot antipsychotic versus oral alternatives for the prevention of violent behaviour in 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.

Pituitary gland shrinkage in bipolar disorder: The role of gender.

BACKGROUND: Hyperactivity of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) has been consistently reported in mood disorders. However, only few studies investigated the Pituitary gland (PG) in Bipolar Disorder (BD) and the results are so far contrasting. Therefore, the aim of this study is to explore the integrity of the PG as well as the role of gender and the impact of clinical measurements on this structure in a sample of BD patients compared to healthy controls (HC). METHODS: 34 BD patients and 41 HC underwent a 1.5 T MRI scan. PG volumes were manually traced for all subjects. Psychiatric symptoms were assessed by means of the Brief Psychiatry Rating Scale, the Hamilton Depression Rating Scale and the Bech Rafaelsen Mania Rating Scale. RESULTS: We found decreased PG volumes in BD patients compared to HC (F = 24.9, p < 0.001). Interestingly, after dividing the sample by gender, a significant PG volume decrease was detected only in female BD patients compared to female HC (F = 9.1, p < 0.001), but not in male BD compared to male HC (F = -0.12, p = 0.074). No significant correlations were observed between PG volumes and clinical variables. CONCLUSIONS: Our findings suggest that BD patients have decreased PG volumes, probably due to the long-term hyperactivity of the HPAA and to the consequent strengthening of the negative feedback control towards the PG volume itself. This alteration was particularly evident in females, suggesting a role of gender in affecting PG volumes in BD. Finally, the absence of significant correlations between PG volumes and clinical variables further supports that PG disruption is a trait feature of BD, being independent of symptoms severity and duration of treatment.