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Background: Systematic data on clinical correlates of mixed features in bipolar disorder are not available, so far. We conducted a systematic review and meta-analysis estimating the association between DSM-5 mixed features and candidate characteristics in depressive and manic/hypomanic episodes. Methods: We included observational studies indexed in the main electronic databases. The association between DSM-5 mixed features and relevant correlates was estimated using odds ratio (OR) and standardized mean difference (SMD) with 95% confidence intervals (CIs), for categorical and continuous variables, respectively. Analyses were based on random effects models. Results: Eight studies were included, involving 3070 individuals (1495 with a major depressive episode and 1575 with hypo/manic episode). No clinical characteristics were associated with mixed features in subjects with a depressive episode. Among subjects with a manic/hypomanic episode, those with mixed features were more likely to have a history of suicide attempts (OR: 2.37; 95%CI: 1.42 to 3.94; I2=39.7%), co-occurring anxiety disorders (OR: 2.67; 95%CI: 1.28 to 5.57; I2=0%), and a rapid cycling course (OR=4.23; 95%CI: 1.29 to 13.81; I2=0%), with less severe manic symptoms (SMD=-0.40; 95%CI: -0.65 to -0.16; I2=0%). Limitations: (1) the heterogeneity of methods across studies and the inconsistency of findings; (2) the limited amount of data on correlates of DSM-5 mixed features; (3) the possible influence of publication bias. Conclusions: Findings of this meta-analysis show that mixed features among individuals with a manic/hypomanic episode may identify a special clinical population, characterized not only by depressive symptoms, but also by anxiety, rapid cycling, and suicidality.

This study, based on the 'Servizi Territoriali Associati per la Ricerca' (STAR) Network Depot Study nationwide baseline data, explored whether individual symptoms severity and clusters might influence the prescription of paliperidone palmitate 1-month (PP1M) vs. aripiprazole monohydrate. The Brief Psychiatric Rating Scale (BPRS) was used to assess psychopathology and relevant symptoms clusters. Drug Attitude Inventory, 10 items, was used to test attitude towards medications. Adherence to treatments was rated according to the Kemp seven-point scale. We assessed for eligibility 451 individuals and, among them, we included 195 subjects (n = 117 who started PPM1 and n = 78 aripiprazole monohydrate). Individuals were comparable in terms of age, gender, treatment years, recent hospitalizations, previous long-acting injectable antipsychotic treatments, additional oral treatments, attitude toward drugs, medication adherence, and alcohol/substance-related comorbidities. Subjects starting PP1M presented higher BPRS overall (P = 0.009), positive (P = 0.015), and negative (P = 0.010) symptom scores compared to subjects starting aripiprazole monohydrate. Results were confirmed by appropriate regression models and propensity score matching analysis. No differences were found comparing the other BPRS subscale scores: affect, resistance, and activation. Clinicians may be more prone to prescribe PPM1, rather than aripiprazole monohydrate, to subjects showing higher overall symptom severity, including positive and negative symptoms. No additional clinical factors influenced prescribing attitudes in our sample.

Objectives The association between post-traumatic stress disorder (PTSD) and metabolic dysfunctions has attracted growing attention in recent years. Understanding and identifying common inflammatory and neuroendocrine mechanisms can help clinicians to improve the treatment and prognosis of these co-occurring conditions. Methods We conducted an overview, summarizing biological mechanisms and related biomarkers underlying the relationship between PTSD and metabolic dysfunctions Results Evidence suggests that PTSD may be associated with metabolic abnormalities. Metabolic syndrome in PTSD may impact both cardiovascular health and central nervous system functions. The role of traumatic events in influencing inflammatory and immuno-metabolic systems seems supported by available studies. Exposure to trauma may determine neuroendocrine responses and long-lasting changes in the regulation of the hypothalamic-pituitary-adrenal axis, affecting its physiological activity Conclusions Dysfunctional adaptation to stress may increase the vulnerability to metabolic abnormalities which, in turn, may favor the occurrence of psychopathological features after traumatic experiences. Approaching PTSD as a systemic condition by assessing, monitoring, and treating metabolic variations may lead to a significant improvement in its management and prognosis. Further research is needed to test novel treatments for PTSD, targeting neuroendocrine and immune-metabolic systems.

S100 calcium-binding protein B (S100B) and neuron-specific enolase (NSE) might be peripheral markers reflecting glia and neuronal abnormalities in subjects with bipolar disorder. We carried out a systematic review and meta-analysis, searching for studies indexed in main electronic databases, to clarify whether S100B and NSE blood levels might be increased in bipolar disorder. Eleven studies met eligibility criteria, with data on S100B levels and/or NSE levels in subjects with bipolar disorder and healthy controls, respectively. Random-effects meta-analysis estimated higher levels of S100B in bipolar disorder (standardized mean difference [SMD] = 0.81; p < .001), with some inconsistency across studies (I2 = 81.7%). Findings were confirmed by relevant sensitivity analyses. Meta-regression analyses did not estimate any effect for tested covariates. On the other hand, no differences in NSE levels between individuals with bipolar disorder and healthy controls were estimated (SMD = −0.32; p = .374), with high heterogeneity across studies (I2 = 89.9%). Meta-regression analyses showed that the effect size was influenced by both mean age (p < .001) and illness duration (p = .001) of subjects with bipolar disorders. Our findings support the hypothesis of a possible role of glial abnormalities in the pathophysiology of bipolar disorder.

Schizophrenia is a severe mental illness causing a high degree of disability. First-and second-generation antipsychotics (FGAs and SGAs) represent key resources for its acute and long-term management. Since a poor adherence to oral treatments may negatively impact the course of the disorder, long-acting injectable antipsychotics (LAIs) are often used to reduce clinical relapses. Notwithstanding their potential beneficial features, LAIs use in clinical practice remains somewhat hampered by the limited amount of relevant systematic information. This review thus aims at providing a clinical, practical guidance for the use of LAIs in the treatment of schizophrenia. We synthetized main information on indications, dosage, and administration of LAIs approved by the US Food and Drug Administration (FDA) and/or in EU countries, as well as evidence from the most recent systematic reviews and meta-analyses. Currently available information, though heterogeneous, shows that LAIs can prevent relapses and rehospitalizations, improving clinical outcomes and favouring sustained remission among people with schizophrenia. The use of SGA LAIs is supported by more robust evidence than FGA LAIs. Along with their positive impact on the prevention of treatment discontinuation, some LAIs might also enhance individual global functioning and quality of life, without additional adverse events or health-care costs, as compared with oral antipsychotics. Although which LAIs can be considered a first-choice option, as well as their superiority over oral antipsychotics, remain unclear issues, this review offers a comprehensive overview of information available on the use of LAIs for people with schizophrenia, providing clinicians with practical guidance in terms of efficacy and acceptability of single agents. Literature gaps and future research needs are also described.

Attention deficit/hyperactivity disorder (ADHD) is associated with poor academic performance also among university students. This relationship may be made more complex by comorbid conditions. The aim of this study was to evaluate the mediating role of anxiety and depressive symptoms in the relationship between ADHD and academic performance. Data were drawn from the CAMPUS study (registration number: 0058642/21), an ongoing survey on university students' mental health. Using a logit model, mediation analyses were carried out to test whether the relationship between ADHD symptoms (assessed by ASRS-5) and academic performance might be mediated by depressive (assessed by PHQ-9) and anxiety (assessed by GAD-7) symptoms. Our results showed that worse academic performance is associated with ADHD symptoms (p < 0.001). However, about 24% of the overall association between ADHD symptoms and academic performance was mediated by depressive symptoms (indirect effect: 0.065, 95%CI 0.022; 0.100), whereas the contribution of anxiety symptoms to the model was not significant. Along with the association between ADHD symptoms and poor academic performance, our findings highlight the key mediating role of depressive symptoms, which may be targeted with tailored support, ultimately improving both the academic performance and the well-being of university students with ADHD.

Background. The balance between neurotoxic and neuroprotective effects of kynurenine pathway (KP) components has been recently proposed as a key element in the pathophysiology of bipolar disorder (BD) and related mood episodes. This comprehensive overview explored the link of KP with symptom severity and other clinical features of BD. Methods. We searched Medline, Embase, and PsycInfo electronic databases for studies assessing the association of peripheral and/or central concentrations of KP metabolites with putative clinical features, including symptom severity and other clinical domains in BD. Results. We included the findings of 13 observational studies investigating the possible variations of KP metabolites according to symptom severity, psychotic features, suicidal behaviors, and sleep disturbances in BD. Studies testing the relationship between KP metabolites and depression severity generated mixed and inconsistent findings. No statistically significant correlations with manic symptoms were found. Moreover, heterogeneous variations of the KP across different clinical domains were shown. Few available studies found (a) higher levels of cerebrospinal fluid kynurenic acid and lower of plasma quinolinic acid in BD with psychotic features, (b) lower central and peripheral picolinic acid levels in BD with suicide attempts, and (c) no significant correlations between KP metabolites and BD-related sleep disturbances. Conclusions. An imbalance of KP metabolism toward the neurotoxic branches is likely to occur in people with BD, though evidence on variations according to specific clinical features of BD is less clear. Additional research is needed to clarify the role of KP in the etiopathogenesis of BD and related clinical features.

The responsiveness of professionals working with children and families is of key importance for child maltreatment early identification. However, this might be undermined when multifaceted circumstances, such as the COVID-19 pandemic, reduce interdisciplinary educational activities. Thanks to technological developments, digital platforms seem promising in dealing with new challenges for professionals’ training. We examined a digital approach to child maltreatment training through the ERICA project experience (Stopping Child Maltreatment through Pan-European Multiprofessional Training Programme). ERICA has been piloted during the pandemic in seven European centers involving interconnected sectors of professionals working with children and families. The training consisted of interactive modules embedded in a digital learning framework. Different aspects (technology, interaction, and organization) were evaluated and trainers’ feedback on digital features was sought. Technical issues were the main barrier, however, these did not significantly disrupt the training. The trainers perceived reduced interaction between participants, although distinct factors were uncovered as potential favorable mediators. Based on participants’ subjective experiences and perspectives, digital learning frameworks for professionals working with children and families (such as the ERICA model nested in its indispensable adaptation to an e-learning mode) can represent a novel interactive approach to empower trainers and trainees to tackle child maltreatment during critical times such as a pandemic, and as an alternative to more traditional learning frameworks.

Background: Subjective well-being in people with schizophrenia is likely to be impaired by positive and negative psychotic symptoms. However, these may impact differentially on hedonic (satisfaction and interest in life) and eudaemonic (optimal psychological and social functioning) components. Aims: We hypothesized that positive symptoms would influence the hedonic component, while negative symptoms would be linked to eudaemonic well-being. Methods: We tested this using longitudinal data (N = 1208) from the EUROSC study. Measures were repeated after 6, 12, 18 and 24 months. Hedonic and eudaemonic features were identified using the Quality of Life Interview. Positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale. We used latent variable structural equation modelling to investigate the impact of positive and negative symptoms at each of the four data points on well-being components 6 months later, controlling for depressed mood. Results: The measurement model yielded acceptable fit. People with higher scores on positive symptoms at a given time-point were more likely to report lower scores for hedonic components six months later (6-, 12-, and 24-month), whereas we found no significant paths from negative symptoms to hedonic or eudaemonic features. Conclusions: Although we found a longitudinal influence of positive symptoms on hedonic well-being, negative symptoms had no effect on either hedonic or eudaemonic components. While symptom reduction strategies may be helpful for hedonic well-being, the amelioration of eudaemonic features may require targeted psychosocial programmes to help individuals attain more rewarding lives.

Background: A dose-response association, suggesting that heavy cannabis users are more likely to report depressive disorders, has been hypothesized. However, evidence is not conclusive, and we aimed at testing the existence of a linear association between different levels of cannabis use and depressive disorders using large, representative, repeated surveys. Methods: We examined prevalence rates of different levels of past-year cannabis use and major depressive episode (MDE), separately for young people (12?17 years) and adults (18?64 years), using data between 2006 and 2015 from the National Survey on Drug Use and Health. Prevalence rates estimates with 95% confidence intervals were computed, and the association between past-year MDE and cannabis use was assessed. We then investigated whether time-period trends existed for MDE and, if so, whether these differed by cannabis use levels. Models included both time period, to evaluate trend changes in past-year MDE from 2006 to 2015, and time period by cannabis level interaction terms. Results: Cannabis users were more likely, using both single-year and pooled survey data, to have suffered from MDE in the past year. Multiple logistic regression models, after adjusting for time period, age, and gender, showed an association between MDE and cannabis use, regardless of its levels. However, a roughly dose-response relationship was detectable only for adults. Trends in past-year MDE prevalence rates among subjects with different levels of cannabis use did not differ from trends among nonusers. Women were more likely to report concurrent past-year MDE and cannabis use than men. Conclusions: Cannabis users have consistently higher prevalence rates of depressive disorders compared with nonusers, suggesting the need for integrated screening and treatment programs to tackle this comorbid condition.

The COVID-19 pandemic has had a severe psychosocial impact on healthcare workers (HCWs). This systematic review and meta-analysis aimed at evaluating the association between individual features and depressive symptoms reported by HCWs during the pandemic. We searched Medline, Embase, and PsycInfo up to 23 June 2020. We included cross-sectional studies testing the association between individual correlates and depressive symptoms in HCWs during the SARS-CoV-2 outbreak. Fourteen studies met inclusion criteria, involving 14,173 HCWs (3,070 with depressive symptoms). Women (OR = 1.50; 95 %CI: 1.28–1.76; I2 = 40.0 %), individuals with suspected/confirmed COVID-19 (OR = 2.10; 95 %CI: 1.64–2.69; I2 = 0 %), and those with an infected family member or friend (OR = 1.67; 95 %CI: 1.37–2.04; I2 = 0%) were more likely to report depressive features, which, instead, were less frequent among doctors (compared with nurses) (OR = 0.80; 95 %CI: 0.66–0.98; I2 = 48.2 %) and HCWs who felt adequately protected (OR = 0.48; 95 %CI: 0.32–0.72; I2 = 36.3 %). Our study provided timely evidence on the correlates of depressive symptoms among HCWs during the pandemic. Early screening is crucial to develop tailored health interventions, redesigning the response to COVID-19.

In recent years we have witnessed a growing interest in the analysis of social media data under different perspectives, since these online platforms have become the preferred tool for generating and sharing content across different users organized into virtual communities, based on their common interests, needs, and perceptions. In the current study, by considering a collection of social textual contents related to COVID-19 gathered on the Twitter microblogging platform in the period between August and December 2020, we aimed at evaluating the possible effects of some critical factors related to the pandemic on the mental well-being of the population. In particular, we aimed at investigating potential lexicon identifiers of vulnerability to psychological distress in digital social interactions with respect to distinct COVID-related scenarios, which could be “at risk” from a psychological discomfort point of view. Such scenarios have been associated with peculiar topics discussed on Twitter. For this purpose, two approaches based on a “top-down” and a “bottom-up” strategy were adopted. In the top-down approach, three potential scenarios were initially selected by medical experts, and associated with topics extracted from the Twitter dataset in a hybrid unsupervised-supervised way. On the other hand, in the bottom-up approach, three topics were extracted in a totally unsupervised way capitalizing on a Twitter dataset filtered according to the presence of keywords related to vulnerability to psychological distress, and associated with at-risk scenarios. The identification of such scenarios with both approaches made it possible to capture and analyze the potential psychological vulnerability in critical situations.

BACKGROUND: The fight against the COVID-19 pandemic seems to encompass a social media debate, possibly resulting in emotional contagion and the need for novel surveillance approaches. In the current study, we aimed to examine the flow and content of tweets, exploring the role of COVID-19 key events on the popular Twitter platform. METHODS: Using representative freely available data, we performed a focused, social media-based analysis to capture COVID-19 discussions on Twitter, considering sentiment and longitudinal trends between January 19 and March 3, 2020. Different populations of users were considered. Core discussions were explored measuring tweets' sentiment, by both computing a polarity compound score with 95% Confidence Interval and using a transformer-based model, pretrained on a large corpus of COVID-19-related Tweets. Context-dependent meaning and emotion-specific features were considered. RESULTS: We gathered 3,308,476 tweets written in English. Since the first World Health Organization report (January 21), negative sentiment proportion of tweets gradually increased as expected, with amplifications following key events. Sentiment scores were increasingly negative among most active users. Tweets content and flow revealed an ongoing scenario in which the global emergency seems difficult to be emotionally managed, as shown by sentiment trajectories. CONCLUSIONS: Integrating social media like Twitter as essential surveillance tools in the management of the pandemic and its waves might actually represent a novel preventive approach to hinder emotional contagion, disseminating reliable information and nurturing trust. There is the need to monitor and sustain healthy behaviors as well as community supports also via social media-based preventive interventions.

Background: Post-stroke depression (PSD) is a common and serious complication after stroke. In this systematic review and meta-analysis, we evaluated the association between early PSD and mortality, considering depressive symptoms occurring within the first 3 months after the neurological event. Methods: This meta-analysis was conducted following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and based on studies indexed till May 2018 in PubMed and Web of Science databases. The relative risk (RR) for mortality in individuals with PSD, as compared with non-depressed ones, was estimated. Findings were pooled according to a random-effects model. Meta-regression and subgroup analyses were carried out. Results: We included seven studies, accounting for 119,075 individuals, of whom 17,609 suffering from an early PSD. We found higher rates of mortality in subjects with PSD as compared with non-depressed ones (RR = 1.50; 95%CI: 1.28 to 1.75; p < 0.001). Heterogeneity across studies was moderate (I2 = 50.7%). Subgroup analysis showed a slightly higher effect of PSD on short-term mortality (RR = 1.70; p < 0.001), as compared with long-term one (RR = 1.35; p = 0.01). According to relevant meta-regression analyses, the estimate was influenced by sample proportion of men (p = 0.043). Conclusions: Despite some limitations, our study shows the negative impact of early PSD on survival rates. Mechanisms underlying this association still need to be elucidated and several interpretations can be hypothesized. Future research should test if an early management of depression may increase life expectancy after stroke.

It is established that purinergic signaling can shape a wide range of physiological functions, including neurotransmission and neuromodulation. The purinergic system may play a role in the pathophysiology of mood disorders, influencing neurotransmitter systems and hormonal pathways of the hypothalamic-pituitary-adrenal axis. Treatment with mood stabilizers and antidepressants can lead to changes in purinergic signaling. In this overview, we describe the biological background on the possible link between the purinergic system and depression, possibly involving changes in adenosine- and ATP-mediated signaling at P1 and P2 receptors, respectively. Furthermore, evidence on the possible antidepressive effects of non-selective adenosine antagonist caffeine and other purinergic modulators is reviewed. In particular, A2A and P2X7 receptors have been identified as potential targets for depression treatment. Preclinical studies highlight that both selective A2A and P2X7 antagonists may have antidepressant effects and potentiate responses to antidepressant treatments. Consistently, recent studies feature the possible role of the purinergic system peripheral metabolites as possible biomarkers of depression. In particular, variations of serum uric acid, as the end product of purinergic metabolism, have been found in depression. Although several open questions remain, the purinergic system represents a promising research area for insights into the molecular basis of depression.

Binge Drinking (BD) is a common risky behaviour that people hardly report to healthcare professionals, although it is not uncommon to find, instead, personal communications related to alcohol-related behaviors on social media. By following a data-driven approach focusing on User-Generated Content, we aimed to detect potential binge drinkers through the investigation of their language and shared topics. First, we gathered Twitter threads quoting BD and alcohol-related behaviours, by considering unequivocal keywords, identified by experts, from previous evidence on BD. Subsequently, a random sample of the gathered tweets was manually labelled, and two supervised learning classifiers were trained on both linguistic and metadata features, to classify tweets of genuine unique users with respect to media, bot, and commercial accounts. Based on this classification, we observed that approximately 55% of the 1 million alcohol-related collected tweets was automatically identified as belonging to non-genuine users. A third classifier was then trained on a subset of manually labelled tweets among those previously identified as belonging to genuine accounts, to automatically identify potential binge drinkers based only on linguistic features. On average, users classified as binge drinkers were quite similar to the standard genuine Twitter users in our sample. Nonetheless, the analysis of social media contents of genuine users reporting risky behaviours remains a promising source for informed preventive programs.

Background: The interaction between positive, negative and depressive symptoms experienced by people with schizophrenia is complex. We used longitudinal data to test the hypothesis that depressive symptoms mediate the links between positive and negative symptoms. Methods: We analyzed data from the European Schizophrenia Cohort, randomly sampled from outpatient services in France, Germany and the UK (N = 1208). Initial measures were repeated after 6 and 12 months. Depressive symptoms were identified using the Calgary Depression Scale for Schizophrenia (CDSS), while positive and negative symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Latent variable structural equation modelling was used to investigate the mediating role of depression assessed at 6 months in relation to the longitudinal association between positive symptoms at baseline and negative symptoms at 12 months. Results: We found longitudinal associations between positive symptoms at baseline and negative symptoms at 12 months, as well as between both of these and CDSS levels at 6 months. However depression did not mediate the longitudinal association between PANSS scores; all the effect was direct. Conclusions: Our findings are incompatible with a mediating function for depression on the pathway from positive to negative symptoms, at least on this timescale. The role of depression in schizophrenic disorders remains a challenge for categorical and hierarchical diagnostic systems alike. Future research should analyze specific domains of both depressive and negative symptoms (e.g. motivational and hedonic impairments). The clinical management of negative symptoms using antidepressant treatments may need to be reconsidered.

Evidence for an association between impaired facial emotion recognition and violence in people with schizophrenia is inconclusive. In particular, the role of misidentification patterns involving specific emotions such as anger and the influence of clinical characteristics on this association remain unclear. In this study, we compared facial emotion recognition performance in age- and gender-matched schizophrenia spectrum disorders subjects with (N = 52) and without (N = 52) a history of violence. Data on current symptom severity, Cluster B personality status, past victimization, and alcohol and substance misuse were also collected. Compared to those without, subjects with a history of violence showed worse facial emotion recognition performances, involving anger, fear, disgust, sadness, and happiness. When formally testing the reporting of angry faces, evidence of enhanced sensitivity to anger was not supported. Finally, when the impact of current symptoms was assessed, higher severity of activation symptoms, including motor hyperactivity, elevated mood, excitement and distractibility, mediated the relationship between history of violence and poor facial emotion recognition performance. As a whole, our findings seem to support the role of perceptual deficits involving different emotions as well as of a mediation played by activation symptoms. Facial emotion recognition deficits associated with the propensity to violence, as well certain symptoms mediating their relationship, should be targeted by specific treatment approaches.

We aimed at clarifying the strength and consistency of the association between cannabis use disorder and suicide attempts in bipolar disorder. We conducted a systematic review and meta-analysis of observational studies providing cross-sectional and longitudinal data on this association. We screened articles indexed in Medline, Embase, PsycINFO databases up to July 2018. The random-effects meta-analysis, based on 6375 subjects from eleven studies, estimated a cross-sectional association between cannabis use disorder and history of suicide attempts (OR = 1.35; p = 0.01; I2 = 41.7%). Meta-regression analyses showed that effect size was not influenced by any study characteristics. Publication bias was not detectable. We could not perform a meta-analysis exploring the longitudinal association between cannabis use disorder and suicide attempts, due to the lack of suitable data. The current evidence highlights a weak association between cannabis use disorder and suicidal attempts in bipolar disorder. Due to the cross-sectional design of included studies, causal inferences could not be explored.

Objectives: Despite growing concerns for non-medical use of prescription pain relievers (NMUPPRs), little is known about the role of comorbid, untreated depressive disorders. Methods: We examined past year rates of NMUPPRs and major depressive episode (MDE), using data between 2008 and 2014 from the National Survey on Drug Use and Health for both youths (12–17 years) and adults (18 or older). Prevalence estimates with 95% confidence intervals were computed. Stratified analyses and generalized linear models were run to examine the association between NMUPPRs and MDE, controlling for treatments received for mental health and/or substance misuse. In order to explore whether MDE effect might change by treatment received, a model with an interaction term including MDE and treatment was fit. Results: Among respondents, about 9% (youths) and 7% (adults) reported past year MDE and about 6% (youths), and 4% (adults) NMUPPRs. About 1.2% (youths) and 0.7% (adults) reported both MDE and NMUPPRs. Those with past year MDE were more likely to report NMUPPRs (RR, 95%CI: 2.60, 2.42–2.80, and 2.64, 2.47–2.82, for youths and adults). Considering the any treatment/MDE interaction on NMUPPRs, MDE risk ratio for subjects who received some treatment (youths: adjusted risk ratio (ARR) = 1.15; adults: ARR = 1.25) was about 70–80% as compared with their untreated counterpart (youths: ARR = 1.57; adults: ARR = 1.54). The likelihood of reporting NMUPPRs amongst respondents who did not receive any treatment was higher for those with past year MDE (main effect: youths ARR = 1.57, p < 0.001; adults ARR = 1.54, p < 0.001). Conclusion: Unrecognized and untreated depressive disorders should be considered for prevention, treatment, and policy implications in order to tackle NMUPPRs epidemic.

A fair amount of subjects with schizophrenia do not respond to clozapine and are defined ‘ultra-resistant’. In this systematic review and meta-analysis, we tested the efficacy of adjunctive second-generation antipsychotics (SGAs) for main symptom domains (positive, negative, and depressive symptoms) in individuals with clozapine-resistant schizophrenia. We searched main electronic databases till December 2017. We included twelve double-blind, randomized, placebo-controlled trials (RCTs), evaluating the efficacy of SGAs for clozapine non/partial responders. We did not find any difference between SGAs and placebo (standardized mean difference, SMD = −0.21; p = 0.170; I2 = 68.0%) in improving positive symptoms. The effect size varied according to RCT duration (p = 0.025) and assessment methods (p = 0.016). Low-moderate effects of SGAs on both negative (SMD = −0.38; p = 0.005; I2 = 62.7%) and depressive symptoms (SMD = −0.35; p = 0.003; I2 = 4.9%), were estimated. In sum, our meta-analysis highlights the lack of efficacy of SGAs as add-on treatment for positive symptoms in clozapine-resistant schizophrenia. A small benefit of SGAs was estimated for both negative and depressive symptoms. Further RCTs are needed to establish efficacy and tolerability of SGAs or other augmentation strategies for different symptoms of clozapine-resistant schizophrenia.

The present study examined the prevalence and correlates of clinical syndromes in a large group (N = 438) of incarcerated violent offenders, looking at differences between inmates with one and those with more than one clinical syndromes. More than a half of the sample (57%) reported clinically relevant symptoms for at least one clinical syndrome (n = 252), and the majority of them (38%) reported more syndromes in comorbidity (n = 169). Increased severity of clinical conditions (none, one, more than one syndrome) corresponded with significantly greater levels of personality disorder traits, psychological symptoms, dissociation, and negative emotionality, with large effect sizes. After controlling for co-occurrence of personality disorder traits and other symptoms, the presence of more than one comorbid syndrome significantly predicted unique variance in dissociation (positively) and positive emotionality (negatively). The presence of one clinical syndrome significantly and positively predicted negative emotionality. Findings support the possibility that the complexity, and not just the presence, of psychopathology could identify different groups of inmates

AIM: Reduced social network (SN) might be associated with a longer duration of untreated psychosis (DUP) in people with first episode psychosis (FEP). We aimed at exploring the specific role of SN confidants on DUP, taking into account cannabis misuse, which is known to influence DUP and might be associated with social functioning. METHODS: People with FEP recently referred to an inner London Early Intervention Service were assessed with standardized instruments exploring SN characteristics, DUP and cannabis misuse. RESULTS: Taking into account cannabis misuse, we found an association between confidants and DUP (P = 0.020), with the higher the number of confidants, the shorter the DUP. CONCLUSIONS: Confidants may provide access to, and perceptions of, social support and this may increase early engagement for people with FEP, reducing DUP and possibly improving outcomes. Future research should identify correlates of small networks of confidants, which could inform early detection community initiatives.

Peripheral biomarkers for suicide have been studied generating mixed results. We investigated the association between serum lipid levels and suicide attempts in subjects with different mental disorders. We conducted a cross-sectional study, including 593 inpatients with schizophrenia spectrum, bipolar, major depressive, and personality disorders, hypothesizing that subjects with lower total cholesterol levels would have higher rates of recent suicide attempts. Contrary to our hypothesis, individuals with lower total cholesterol levels (<160 mg/dL) showed lower rates also of suicide attempts (OR adjusted for age and gender: 0.56; one-tailed p = 0.03). Further logistic regression models failed to estimate any association of continuous levels between total/low-density lipoprotein (LDL) cholesterol/ triglycerides, and suicide attempts, also considering diagnosis and suicide methods. An association between lipid profile and suicide attempts in subjects with mental disorders is not fully supported. Further research is needed to clarify the role of biomarkers in suicidal behaviors

Objectives. Since evidence on executive control among women with Anorexia or Bulimia Nervosa (AN/BN) are somehow inconclusive, we aimed to explore whether performance in set-shifting in AN/BN might be influenced by Facial Emotion Recognition (FER). Methods. We randomly recruited women with a diagnosis of AN or BN, from an Eating Disorders Outpatient Clinic in Italy, as well as healthy controls (HCs). We evaluated with established tools: diagnosis (Eating Disorder Examination- EDE-17.0), executive control (Intra-Extra Dimensional Set Shift-IED) and FER (Ekman 60 Faces Test-EK-60F). Univariate distributions by diagnostic subgroups were assessed on sociodemographic and clinical variables, which were selected for subsequent multiple linear regression analyses. Results. Women with AN performed significantly worse than HCs on IED adjusted total errors. HCs scored significantly better than AN and BN on EK-60F fear subscale. Although IED set shifting was associated (p = 0.008) with AN, after controlling for age, EK- 60F fear subscale, alexithymia and depression (i.e., clinically relevant covariates identified a priori from the literature, or associated with AN/BN at univariate level), this association could not be confirmed. Conclusions. Impaired executive control may not be a distinctive feature in women with AN, since several clinical characteristics, including fear recognition ability, are likely to have an important role. This has significant implications for relevant interventions in AN, which should aim at also improving socio-emotional processing.

Objectives The clinical and psychopathological relationships between substance use and suicidal behaviours are deserving growing attention. Understanding and identifying factors that may be associated with suicidal behaviours can help clinicians to early detect high-risk individuals. Methods We conducted a narrative review, summarising main epidemiological data from longitudinal studies, on the potential association between cannabis use and suicidal behaviours. In addition, we discuss possible psychopathological models that may explain and disentangle this clinical relationship. Results Individuals who use cannabis, the most common psychoactive drug apart from alcohol and nicotine, may have higher risk of suicidal behaviours. Despite the mixed findings, evidence seems to suggest that an early and heavy cannabis use may be associated with suicidal ideation, attempt, and completion. Conclusions Findings from our review show that it is likely that cannabis is associated with increased rates of suicidal behaviours. This relationship could be explained by the reciprocal influence of cannabis on severity of depression, psychotic features, and impulsivity. Cannabis may play a key role in the complex clinical pathways that link mental disorders and suicide-related behaviours. Nevertheless, various potential mechanisms and contributing factors to this association remain to be investigated.

Previous research has hypothesized a role for serum uric acid as a marker of mental disorders and related behaviors, possibly due to its link with purinergic transmission and antioxidant activity. We tested the association of serum uric acid levels with specific behavioral and clinical characteristics in 99 individuals suffering from major affective disorders. Subjects were assessed and interviewed using the Kessler Psychological Distress Scale, the Columbia-Suicide Severity Rating Scale, the Modified Overt Aggression Scale, and the Barratt Impulsiveness Scale. We found that psychological distress and suicidal ideation severity were associated with lower uric acid serum levels. On the other hand, verbal aggression and history of violence were associated with higher levels of serum uric acid. However, according to linear regression analyses, there were no behavioral and clinical characteristics independently associated with serum uric acid. Serum uric acid levels were influenced by creatinine and BMI, as well as, possibly, by white blood cells count and gender. Despite some limitations, these results suggest that no behavioral / clinical features are associated with variations of serum uric acid, which rather seem attributable to specific biochemical and metabolic parameters. Nevertheless, the role of purinergic system in different mental disorders and behavioral abnormalities, deserves further research

BACKGROUND: Little is known about the influence of contextual characteristics on comorbid substance use and serious mental illness (SMI). AIMS: To explore the role of poverty on comorbid SMI and cannabis use. METHODS: We used data from the 2015 National Survey on Drug Use and Health, considering those in poverty, with income under 100% of the US poverty threshold. RESULTS: People in poverty were more likely to suffer from concurrent SMI and cannabis use (3.07%, 95% confidence interval (CI):1.84%; 5.07%), even controlling for gender, age, tobacco and alcohol use (odds ratio (OR) = 2.77, 95% CI: 1.27; 6.03, p = .010). CONCLUSION: The magnitude of the association between SMI and cannabis use is influenced by poverty status. More research on potential mediators like income inequality and impoverished social capital is needed

OBJECTIVES: Binge drinking (BD) among young people has significant public health implications. Thus, there is the need to target users most at risk. We estimated the discriminative accuracy of an innovative model nested in a recently developed e-Health app (Digital-Alcohol RIsk Alertness Notifying Network for Adolescents and young adults [D-ARIANNA]) for BD in young people, examining its performance to predict short-term BD episodes. METHODS: We consecutively recruited young adults in pubs, discos, or live music events. Participants self-administered the app D-ARIANNA, which incorporates an evidence-based risk estimation model for the dependent variable BD. They were re-evaluated after 2 weeks using a single-item BD behavior as reference. We estimated D-ARIANNA discriminative ability through measures of sensitivity and specificity, and also likelihood ratios. ROC curve analyses were carried out, exploring variability of discriminative ability across subgroups. RESULTS: The analyses included 507 subjects, of whom 18% reported at least 1 BD episode at follow-up. The majority of these had been identified as at high/moderate or high risk (65%) at induction. Higher scores from the D-ARIANNA risk estimation model reflected an increase in the likelihood of BD. Additional risk factors such as high pocket money availability and alcohol expectancies influence the predictive ability of the model. CONCLUSIONS: The D-ARIANNA model showed an appreciable, though modest, predictive ability for subsequent BD episodes. Post-hoc model showed slightly better predictive properties. Using up-to-date technology, D-ARIANNA appears an innovative and promising screening tool for BD among young people. Long-term impact remains to be established, and also the role of additional social and environmental factors

Background: Randomised placebo-controlled trials investigating treatments for bipolar disorder have been hampered by wide variations of active drugs and placebo clinical response rates. It is important to estimate whether the active drug or placebo response has a greater influence in determining the relative efficacy of drugs for psychosis (antipsychotics) and relapse prevention (mood stabilisers) for bipolar depression and mania. Methods: We identified 53 randomised, placebo-controlled trials assessing antipsychotic or mood stabiliser monotherapy (‘active drugs’) for bipolar depression or mania. We carried out random-effects meta-regressions, estimating the influence of active drugs and placebo response rates on treatment relative efficacy. Results: Meta-regressions showed that treatment relative efficacy for bipolar mania was influenced by the magnitude of clinical response to active drugs (p=0.002), but not to placebo (p=0.60). On the other hand, treatment relative efficacy for bipolar depression was influenced by response to placebo (p=0.047), but not to active drugs (p=0.98). Conclusions: Despite several limitations, our unexpected findings showed that antipsychotics / mood stabilisers relative efficacy for bipolar depression seems unrelated to active drugs response rates, depending only on clinical response to placebo. Future research should explore strategies to reduce placebo-related issues in randomised, placebo-controlled trials for bipolar depression.

Aim: Reduced social network (SN) might be associated with a longer duration of untreated psychosis (DUP) in people with first episode psychosis (FEP). We aimed at exploring the specific role of SN confidants on DUP, taking into account cannabis misuse, which is known to influence DUP and might be associated with social functioning. Methods: People with FEP recently referred to an inner London Early Intervention Service were assessed with standardized instruments exploring SN characteristics, DUP and cannabis misuse. Results: Taking into account cannabis misuse, we found an association between confidants and DUP (P = 0.020), with the higher the number of confidants, the shorter the DUP. Conclusions: Confidants may provide access to, and perceptions of, social support and this may increase early engagement for people with FEP, reducing DUP and possibly improving outcomes. Future research should identify correlates of small networks of confidants, which could inform early detection community initiatives

Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges’ g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges’ g = −0.30; p = 0.003). Overall between-study heterogeneity was high (I2 = 76.3%). The effect was significant among studies including drug naïve/free MDD individuals (Hedges’ g = −0.55; p = 0.023), but not among those involving treated subjects (Hedges’ g = −0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I2 = 79.2%), increased after treatment (MD = +0.71 mg/ dL; p < 0.001), regardless of follow-up duration (p = 0.518). Our meta-analysis shows that subjects with MDD have lower levels of uric acid. Since antidepressant treatment seems to influence this association, our findings support the hypothesis that uric acid levels may represent a state marker of MDD. Nevertheless, the potential role of additional factors that might clarify the nature of this association deserves further research.

Background: In the past decade, several smoking cessation interventions have been developed and implemented through information and communication technology (ICT). Evidence suggests that they might be suitable for large-scale public health interventions, based on updated communication media characteristics in terms of interplay between technology and graphical user interface, reaching high numbers of individuals. Objectives: We aimed at estimating web/text-based interventions effectiveness as compared with approaches routinely used for general population, that is smoking assessment or non-electronic self-help materials. Methods: A systematic review and meta-analysis was performed searching through PubMed, Embase and PsycInfo databases, as well as references of relevant papers. Heterogeneity and risk of bias were evaluated following standard methods. In addition, we performed meta-regression analyses testing if candidate covariates moderate the overall effect. Results: Slight but significant effectiveness was found for eHealth interventions over control conditions (RR = 1.28, 95% CI: 1.14–1.45). Meta-regressions showed similar findings for web- and text-based interventions. The effect seemed moderated by the follow-up period, being higher at 3 months and lower at 6/7 months follow-up. Conclusions: Our results outline moderate effectiveness of web/text-based interventions. However, a paucity of properly controlled studies and lack of information on several effect modifiers still hamper the development and implementation of smoking cessation interventions through ICT

Background Since bipolar disorder seems to be associated with purinergic system dysfunction, allopurinol might be effective in treating symptoms of mania. Aims To estimate the efficacy and tolerability of allopurinol as adjunctive treatment for mania symptoms in people with bipolar affective disorder. Method We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the effects of adjunctive allopurinol and placebo on mania symptom changes. Results Five RCTs were included in the meta-analysis. Participants with allopurinol augmentation had a significantly greater decrease in mania symptoms than those with placebo (SMD =70.34, P = 0.007), especially in people with the most severe forms of mania. Remission rates, although based on only two studies (n = 177), were significantly higher among individuals receiving allopurinol, whereas for discontinuation and side-effects no difference was found. Conclusions Our finding of a small to moderate effect size and overall low evidence for add-on allopurinol in reducing mania symptoms indicate that its use in routine practice needs further elucidation.