An extensive literature regarding gender differences relevant to several aspects of schizophrenia is nowadays available. It includes some robust findings as well as some inconsistencies. The identification of gender differences and the understanding of their explanations may help to clarify the underlying etiopathogenetic mechanisms of specific aspects of the disorder.

The present study aimed at investigating gender differences on premorbid, clinical, cognitive and outcome indices, as well as their impact on recovery, in a large sample of patients with schizophrenia recruited within the multicenter study of the Italian Network for Research on Psychoses.

State-of-the-art instruments were used to assess the investigated domains. Group comparisons between male and female patients were performed on all considered indices. The associations of premorbid, clinical and cognitive indices with recovery in the two patient groups were investigated by means of multiple regressions.

Males with respect to females had a worse premorbid adjustment – limited to the academic dimension – an earlier age of onset, a higher frequency of history of substance and alcohol abuse, more severe negative symptoms (both avolition and expressive deficit), positive symptoms and impairment of social cognition. No gender difference was observed in neurocognition nor in the rates of recovery.

Although males showed some disadvantages in the clinical picture, this was not translated into a worse outcome. This finding may be related to the complex interplay of several factors acting as predictors or mediators of outcome.

No significant relationships.

Evidence suggests that cognitive subtypes exist in schizophrenia that may reflect different neurobiological trajectories. We aimed to identify whether IQ-derived cognitive subtypes are present in early-phase schizophrenia-spectrum disorder and examine their relationship with brain structure and markers of neuroinflammation.

161 patients with recent-onset schizophrenia spectrum disorder (<5 years) were recruited. Estimated premorbid and current IQ were calculated using the Wechsler Test of Adult Reading and a 4-subtest WAIS-III. Cognitive subtypes were identified with k-means clustering. Freesurfer was used to analyse 3.0 T MRI. Blood samples were analysed for hs-CRP, IL-1RA, IL-6 and TNF-α.

Three subtypes were identified indicating preserved (PIQ), deteriorated (DIQ) and compromised (CIQ) IQ. Absolute total brain volume was significantly smaller in CIQ compared to PIQ and DIQ, and intracranial volume was smaller in CIQ than PIQ (F(2, 124) = 6.407, p = 0.002) indicative of premorbid smaller brain size in the CIQ group. CIQ had higher levels of hs-CRP than PIQ (F(2, 131) = 5.01, p = 0.008). PIQ showed differentially impaired processing speed and verbal learning compared to IQ-matched healthy controls.

The findings add validity of a neurodevelopmental subtype of schizophrenia identified by comparing estimated premorbid and current IQ and characterised by smaller premorbid brain volume and higher measures of low-grade inflammation (CRP).

Obstructive pathology is a benign condition of the salivary glands that can affect elderly and co-morbid people. Sialoendoscopy is a minimally invasive surgical procedure with a success rate comparable to standard sialoadenectomy and has the advantage that it can be performed under local anaesthesia.

This study aimed to assess sialoendoscopy benefits in elderly patients unfit for general anaesthesia. A group of elderly patients (aged 65 years or more) undergoing sialoendoscopy under local anaesthesia were evaluated. Age, co-morbidities, surgical time, hospital stay, and complication and recurrence rates were assessed.

Nineteen sialoendoscopies were performed in 18 elderly patients with a mean age of 69.7 ± 5.6 years, with some of them suffering from multiple co-morbidities. Surgery was successful in 16 patients, while surgery was unsuccessful in 2 patients because of intraglandular stones. The average surgical duration was 54.5 ± 30.1 minutes, and all patients were discharged 2–3 hours after surgery. No post-operative complications were found and only one patient had recurrence during follow up.

Sialoendoscopy under local anaesthesia is a safe and effective procedure in elderly patients who are more prone to complications.

Despite innovative treatments, the impairment in real-life functioning in subjects with schizophrenia (SCZ) remains an unmet need in the care of these patients. Recently, real-life functioning in SCZ was associated with abnormalities in different electrophysiological indices. It is still not clear whether this relationship is mediated by other variables, and how the combination of different EEG abnormalities influences the complex outcome of schizophrenia.

The purpose of the study was to find EEG patterns which can predict the outcome of schizophrenia and identify recovered patients.

Illness-related and functioning-related variables were measured in 61 SCZ at baseline and after four-years follow-up. EEGs were recorded at the baseline in resting-state condition and during two auditory tasks. We performed Sparse Partial Least Square (SPLS) Regression, using EEG features, age and illness duration to predict clinical and functional features at baseline and follow up. Through a Linear Support Vector Machine (Linear SVM) we used electrophysiological and clinical scores derived from SPLS regression, in order to classify recovered patients at follow-up.

We found one significant latent variable (p<0.01) capturing correlations between independent and dependent variables at follow-up (RHO=0.56). Among individual predictors, age and illness-duration showed the highest scores; however, the score for the combination of the EEG features was higher than all other predictors. Within dependent variables, negative symptoms showed the strongest correlation with predictors. Scores resulting from SPLS Regression classified recovered patients with 90.1% of accuracy.

A combination of electrophysiological markers, age and illness-duration might predict clinical and functional outcome of schizophrenia after 4 years of follow-up.

During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent.

In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice.

Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.

This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.

The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.

Several recommendations are provided for the identification of secondary negative symptoms in clinical settings.

The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.

The aim of the present study was to assess sociodemographic and clinical differences between inpatients with major mood disorders and the cyclothymic phenotype, and pure BDs or MDDs.

Participants were 281 adult inpatients consecutively admitted to the Department of Psychiatry of the Sant'Andrea University Hospital in Rome, Italy, between January 2008 and June 2010. The patients completed the Hamilton Scale for Depression, the Young Mania Rating Scale, the TEMPS-A, and the Beck Hopelessness Scale.

38.7% of the MDD patients and 48.3% of the BD patients satisfied criteria to be included in the cyclothymic groups. Above 92% of the patients with the cyclothymic phenotype reported suicidal ideation at the item#3 of the HAMD17. Furthermore, patients with the cyclothymic phenotype reported higher hopelessness than other patients.

Our results support the clinical usefulness of the concept of soft bipolar spectrum. Patients with the cyclothymic phenotype differ from pure MDD patients and BD patients for temperamental profile and clinical variables.

Schizophrenia patients experience severe difficulties in a range of common activities, defined 'functional milestones' (i.e. marriage, employment, self-supported living).

This study investigated the impairment in functional milestones in treatment resistant schizophrenia (TRS), compared to other severe disabling psychiatric conditions. Moreover, we evaluated whether multiple clinical and psychopathological features may be predictors of outcome in such functional milestones.

157 patients were enrolled and subdivided in four groups by diagnosis: anxious-depressive spectrum, bipolar disorder spectrum, schizophrenia responder patients, TRS patients. Demographic, clinical and social data were collected. Patients underwent psychopathological, psychosocial and cognitive functioning assessments. Positive and Negative Syndrome Scale (PANSS), Personal and Social Performance (PSP) scale, Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), List Learning task for Verbal Memory, Digit Sequencing task for Working Memory, Category Instances task for Verbal Fluency and Tower of London task for Problem Solving were administered. Data were analyzed by ×2 test, ANOVA test and Kruskal-Wallis test. Stepwise multivariate regression was used to correlate functional outcomes to clinical and psychopathological variables.

TRS patients were more severely impaired in all psychosocial areas explored, were exposed to higher antipsychotic doses, had a higher number of hospitalizations, had higher scores on psychopathological rating scales and performed worse on the verbal memory task. Outcomes in functional milestones were more correlated to clinical/psychopathological variables in TRS than in the other groups.

Psychosocial impairment, clinical, and psychopathological features generate a vicious circle in TRS, which is less evident in other disabling psychiatric conditions.

Negative symptoms are a core feature of schizophrenia but their pathophysiology remains elusive. They cluster in a motivation-related domain, including apathy, anhedonia, asociality and in an expression-related domain, including alogia and blunted affect.

Our aim was to investigate the different neurobiological underpinnings of the two domains using the brain electrical microstates (MS), which reflect global patterns of functional connectivity with high temporal resolution.

We recorded multichannel resting EEGs in 142 schizophrenia patients (SCZ) and in 64 healthy controls (HC), recruited to the Italian network for research on psychoses study. Four microstates (MS) classes were computed from resting EEG data using the K-Mean clustering algorithm. Pearson's coefficient was used to investigate correlations of microstates measures with negative symptom domains, assessed by the Brief Negative Symptoms Scale (BNSS).

SCZ, in comparison to HC, showed increased contribution and duration of MS-C. Only the avolition domain of BNSS correlated with the contribution and occurrence of MS-A. Within the same domain, anticipatory anhedonia, apathy and asociality, but not consummatory anhedonia, were positively correlated with contribution and occurrence of microstate A. Asociality was also negatively correlated with contribution and occurrence of MS-D.

Our findings support different neurobiological underpinnings of the negative symptom domains, avolition and expressive deficit. Furthermore, our results lend support to the hypothesis that only anticipatory anhedonia is linked to the avolition domain of the negative symptoms. Mixed results in the literature concerning the presence of MS-A and D abnormalities in schizophrenia might be related to the syndrome heterogeneity.

The authors have not supplied their declaration of competing interest.

Avolition represents an important domain of negative symptoms in schizophrenia with a strong impact on functional outcome. Primary and persistent avolition is refractory to available pharmacological and psychological treatments. A better understanding of its pathophysiological mechanisms is fundamental to promote development of new treatments. Recent models of avolition converge on dopaminergic circuits involved in motivation and its translation in goal-directed behavior. Deficits in task-related activation or connectivity within mesolimbic and mesocortical dopamine circuits were reported in schizophrenia but the relationship with avolition was not fully established.

The present study aimed to investigate resting-state functional connectivity (RS-FC) within the motivation circuits in schizophrenia patients and its relationships with primary and persistent avolition.

RS-FC, using VTA as a seed region, was investigated in 22 healthy controls (HC) and in 26 schizophrenia patients (SCZ) divided in high (HA) and low avolition (LA) subgroups. Avolition was assessed using the Schedule for the Deficit Syndrome.

HA, in comparison to LA and HC, showed significantly reduced RS-FC with the right ventrolateral prefrontal cortex (R-VLPFC), right insula (R-INS) and right lateral occipital cortex (R-LOC). The RS-FC of these regions was negatively correlated to avolition.

Our findings demonstrate that avolition in schizophrenia is linked to dysconnection of VTA from key cortical regions involved in retrieval of outcome values of instrumental actions to motivate behavior.

AM received honoraria or advisory board/consulting fees from the following companies: Janssen Pharmaceuticals, Otsuka, Pfizer and Pierre Fabre. SG received honoraria or advisory board/consulting fees from the following companies: Lundbeck, Janssen Pharmaceuticals, Hoffman-La Roche, Angelini-Acraf, Otsuka, Pierre Fabre and Gedeon-Richter. All other Authors declare no potential conflict of interest.

The effects of chronic antipsychotic administration on the human brain are debated. In particular, first-generation (FGAs) and second-generation antipsychotics (SGAs) seem to have different impacts on brain function and structure in subjects with schizophrenia. Few studies have investigated the effect of chronic administration of FGAs and SGAs on indices of brain function, such as event-related potentials (ERP) or neuropsychological performance.

Within the Italian Network for Research on Psychoses study, subjects stabilized on FGAs or SGAs were compared on P300, an ERP component, thought to reflect attention, working memory and context integration and on neurocognitive indices.

ERPs were recorded in 110 chronic, stabilized patients with Schizophrenia (28 used FGAs) during a standard auditory oddball task. P300 latency and amplitude were assessed at Pz channel. MATRICS Consensus Cognitive Battery (MCCB) was used for cognitive assessment.

Compared with the SGAs group, patients on FGAs showed significant increased P300 latency (P = 0.003; Cohen's d = 0.67) and significant decreased P300 amplitudes (P = 0.023; Cohen's d = 0.38). The two groups did not differ on psychopathology and MCCB scores. Multiple linear regressions revealed that “FGAs vs. SGAs” (β = 0.298, P = 0.002) and MCCB neurocognitive composite T-score (β = –0.273, P = 0.004) were independent predictors of P300 latency, whereas only age (β = –0.220, P = 0.027) was an independent predictor of P300 amplitude.

FGAs seem to affect the functional brain activity more than SGAs, particularly slowing cortical processing. Our results suggest that discrepant findings concerning P300 latency in schizophrenia might be related to the type of antipsychotic treatment used. Longitudinal studies are needed to further address this issue.

The authors have not supplied their declaration of competing interest.

Negative symptoms have long been recognized as a central feature of schizophrenia, which limit recovery, having a strong negative impact on real-life functioning. External validators of the negative symptoms domains might help refining hypotheses on their pathophysiological basis.

The objective of this study was to evaluate, in the context of the multicenter study of the Italian Network for Research on Psychoses, the relationships between auditory event-related potentials (ERPs) components and negative symptom domains in patients with schizophrenia (SCZ).

We examined ERPs recorded during an auditory odd-ball task in 115 chronic stabilized SCZ (78% on second-generation antipsychotics) and 62 matched healthy controls (HC). Negative symptoms were assessed using the Brief Negative Symptom Scale.

Our main findings included significant N100 and P3b amplitude reductions in SCZ compared to HC. P3b amplitude did not correlate with any negative symptom domain, while N100 amplitude correlated with both anhedonia and avolition domains.

Avolition and anhedonia, often clustering in the same factor, are related to abnormalities of early components of the ERPs correlated with perceptual and automatic attention processes. None of the negative symptom domains is associated with abnormalities of the later stages indexed by P3 amplitude.

The authors have not supplied their declaration of competing interest.

Impaired motivation is considered a fundamental aspect of the Avolition domain of negative symptoms. The ventral tegmental area (VTA) contains the highest number of DA neurons projecting to the brain areas involved in motivation-related processes.

The aim of our study was to investigate by functional MRI the resting-state functional connectivity (RS-FC) of the VTA in patients with schizophrenia and its relationships with real-life motivation and avolition.

The RS-FC was investigated in 22 healthy controls (HC) and in 26 schizophrenia patients (SCZ) treated with second generation antipsychotics only and divided in high (HA = 13) and low avolition (LA = 13) subgroups. We used the Quality of Life Scale and the Schedule for the Deficit Syndrome to assess real-life motivation and avolition, respectively.

HA, as compared to LA and HC, showed a reduced RS-FC of VTA with the right ventrolateral prefrontal cortex (R VLPFC), right posterior insula (R pINS) and right lateral occipital cortex (R LOC). The RS-FC for these regions was positively correlated with motivation in the whole sample and negatively correlated with avolition in schizophrenia patients.

Our findings demonstrate that motivational deficits in schizophrenia patients are linked to reduced functional connectivity in the DA circuit involved in retrieval of the outcome values of different actions to guide behavior. Further characterization of the factors modulating the functional connectivity in this circuit might foster the development of innovative treatments for avolition.

The authors have not supplied their declaration of competing interest.

In subjects with schizophrenia (SCZ), the disorganization factor was found to be a strong predictor of real-life functioning. “Conceptual disorganization” (P2), “difficulties in abstract thinking” (N5) and “poor attention” (G11) are considered core aspects of the disorganization factor, as assessed by PANSS. The overlap of these items with neurocognitive functions is debated and should be further investigated.

Within the Italian network for research on psychoses study, electrophysiological and neurocognitive correlates of the disorganization factor and its component items were investigated.

Resting state EEGs were recorded in 145 stabilized SCZ and 69 matched healthy controls (HC). Spectral amplitude (SAmp) was averaged in nine frequency bands. MATRICS consensus cognitive battery (MCCB) was used for neurocognitive assessment. Band SAmp differences and correlations with psychopathology and MCCB scores were explored by global randomization statistics.

SCZ showed increased delta, theta, and beta1 and decreased alpha2 SAmp. A negative correlation between alpha1 and disorganization was observed in SCZ. At the item level, only N5 showed this correlation. MCCB neurocognitive composite was associated with P2 and N5 but not with alpha1 SAmp.

Our findings suggest an heterogeneity of the disorganization dimension and a partial overlap with neurocognitive domains. The N5, “difficulties in abstract thinking”, had a unique association with alpha1 SAmp, which is thought to be involved in the formation of conceptual maps.

The authors have not supplied their declaration of competing interest.

Several studies show that attention-deficit/hyperactivity disorder (ADHD) may persist into adulthood, increasing the risk of antisocial behaviour, drug abuse, psychiatric comorbidities, aggressive behaviour, social impairment and suicide risk.

Analyze correlations among ADHD, substances abuse, alcoholism and suicide risk.

The aim of our study is to better understand the clinical features of ADHD during adulthood.

We analyzed the presence of ADHD symptoms, suicide risk and levels of hopelessness, alcoholism and substance abuse in a sample of 50 (40% males) in/outpatients of S. Andrea Hospital in Rome, between February and May 2016. We administered the following scales: Adult-Self Report Scale (ASRS), Columbia Suicide Severity Rating Scale (C-SSRS), Beck Hopelessness Scale (BHS), Michigan Alcoholism Screening Test (MAST), Drug Abuse Screening Test (DAST).

In our sample of 50 adult patients, 20% had ADHD symptoms (10 subjects). We found that those with ADHD showed more frequently death desires (85.7%; χ2 = 1.31; P = 0.25) and higher levels of hopelessness (66.7%; χ2 = 0.83; P = =0.36) if compared to subjects without ADHD symptoms (respectively 63% and 45.8%). In the overall group of ADHD patients, 10% showed severe alcoholism, 20% (χ2 = 1.39; P = 0.49) had a borderline behavior, whereas 40% presented a substance abuse (χ2 = 1.75; P = 0.18).

ADHD may represent a psychiatric disorder with an increased suicide risk. It would be important to screen for suicidality and comorbid symptoms routinely in ADHD in order to improve the treatment of the patients.

The authors have not supplied their declaration of competing interest.

Several studies show that the first period after discharge has an higher suicide risk.

Following up psychiatric inpatients after discharge may be important in order to better understand the risk and the protective factors of suicide.

The aim of our follow-up study is to evaluate the predictive factors of suicide in a sample of psychiatric inpatients after discharge.

We analyzed the temperament and the levels of hopelessness, depression, suicide risk in a sample of 87 (54% males) inpatients at time T0 (during the hospitalization), T1 (12 months after discharge) and T2 (8 months after T1). We administered the following scales: BHS, MINI, TEMPS, GMDS, CGI.

A statistically significant difference on the risk of suicide with substance abuse was found among patients who were followed up and who refused to participate, respectively at T1 (χ24 = 2.61; P < 0.05) and T2 (χ24 = 1.57; P = 0.05). At T1, 4 patients attempted suicide and 18 showed suicidal ideation. In the second follow-up, 1 patient successful committed suicide, 1 subject attempted suicide and 10 patients showed suicidal ideation. Patients with suicidal ideation at T1 showed higher levels of hopelessness and a diagnosis of bipolar disorder type I (χ24 = 10.28; P = 0.05). Sixty-seven percent of subjects with suicidal ideation showed higher scores in the BHS at T1. Significant differences were found on the anxious temperament at T2 between two groups.

The follow-up could represent a significant strategy to prevent suicide in psychiatric patients.

The authors have not supplied their declaration of competing interest.

Suicidal behaviour and drug and alcohol dependence represent two different aspects of self-destructive behavior.

We evaluated the relationship between suicidal behavior and substance and alcohol addiction. It was investigated the role of childhood trauma in these self-destructive behaviors and in the development of the two mental constructions of hopelessness and mentalization.

We also assessed how a high level of hopelessness could affect suicidal ideation and how low or absent capacity of mentalization could influence the development of substance and/or alcohol addiction.

This naturalistic, observational study included 50 patients (mean age = 46.54; S.D = 14.57) recruited from the department of psychiatry (n = 18) and the centre for suicide prevention (n = 32) of Sant’Andrea Hospital (Rome). Different questionnaires were administered to each patient from February to May 2016.

There was not a statistically significant relationship between suicidal behavior and addict behavior. Childhood trauma resulted a risk factor for alcohol abuse with a relationship that tended to significance (P = 0.07). Physical and sexual abuses were significantly associated with addiction (respectively P = 0.014; P = 0.033). It was showed a statistically significant interaction between high level of hopelessness and suicidal ideation (P = 0.037). The absence of mentalization was related to the absence of alcohol abuse (P = 0.061). Finally, trauma experienced during childhood was associated with high level of hopelessness (P = 0.005).

Suicidal behavior is influenced indirectly by a childhood traumatic experience that conditioning the level of hopelessness. Childhood trauma affected directly the development of drug abuse and alcoholism. The capacity of mentalization was not related with childhood trauma.

The authors have not supplied their declaration of competing interest.

Early intervention services (EIS) can significantly reduce the rate of relapse, risk of suicide and number of hospital admissions for people with first episode of psychosis (FEP). However, care pathways in FEP can be complex, thus extending the period before patients commence appropriate treatment. Recently in the UK, guidelines have set a limit of two-weeks before patients with a FEP receive treatment at EIS.

We explored the impact of this new policy on referrals to an EIS in the area City and Hackney, London, which has one of the highest incidence of psychosis in the UK.

Referrals from 6 months of 2015 have been compared with the data from the same period of 2016, once the waiting standard had been implemented.

We observed more than a two-fold increase in the monthly number of referrals (9.4 in 2015; 20 in 2016) and this wasn’t due to a rise of inappropriate referrals (2.23% in 2015; 1.53% in 2016). Moreover the number of referrals doubled further when, in addition, the City & Hackney EIS went from a 18–35-year-service to an “ageless” adult service.

The recent focus on FEP in the UK might have increased awareness and reduced stigma, leading to the increment in referrals. Also, shortening the waiting time made the service more accessible for those that would have gave up in front of a longer waiting list. Interestingly enough a peak in the number of referrals has been observed from September 2016 when another standard was implemented.

The authors have not supplied their declaration of competing interest.