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Background Identification of the predominant polarity, i.e. hypomanic/manic (mPP) or depressive predominant polarity (dPP), might help clinicians to improve personalised management of bipolar disorder. Aims We performed a systematic review and meta-analysis to estimate prevalence and correlates of mPP and dPP in bipolar disorder. Method The protocol was registered in the Open Science Framework Registries (https://doi.org/10.17605/OSF.IO/8S2HU). We searched main electronic databases up to December 2023 and performed random-effects meta-analyses of weighted prevalence of mPP and dPP. Odds ratios and weighted mean differences (WMDs) were used for relevant correlates. Results We included 28 studies, providing information on rates and/or correlates of mPP and dPP. We estimated similar rates of mPP (weighted prevalence = 30.0%, 95% CI: 23.1 to 37.4%) and dPP (weighted prevalence = 28.5%, 95% CI: 23.7 to 33.7%) in bipolar disorder. Younger age (WMD = -3.19, 95% CI: -5.30 to -1.08 years), male gender (odds ratio = 1.39, 95% CI: 1.10 to 1.76), bipolar-I disorder (odds ratio = 4.82, 95% CI: 2.27 to 10.24), psychotic features (odds ratio = 1.56, 95% CI: 1.01 to 2.41), earlier onset (WMD = -1.57, 95% CI: -2.88 to -0.26 years) and manic onset (odds ratio = 13.54, 95% CI: 5.83 to 31.46) were associated with mPP (P < 0.05). Depressive onset (odds ratio = 12.09, 95% CI: 6.38 to 22.90), number of mood episodes (WMD = 0.99, 95% CI: 0.28 to 1.70 episodes), history of suicide attempts (odds ratio = 2.09, 95% CI: 1.49 to 2.93) and being in a relationship (odds ratio = 1.98, 95% CI: 1.22 to 3.22) were associated with dPP (P < 0.05). No differences were estimated for other variables. Conclusions Despite some limitations, our findings support the hypothesis that predominant polarity might be a useful specifier of bipolar disorder. Evidence quality was mixed, considering effects magnitude, consistency, precision and publication bias. Different predominant polarities may identify subgr

Introduction: The efficacy of trazodone for several psychopathologic dimensions of depression has been shown in the literature. Trazodone has been widely used in some clinical contexts (e.g. for insomnia and depression in the elderly). However, the role of trazodone in several aspects of depression is not well known. Area covered: Eight experts from academic and medical centers across Italy met to identify the difficulties and barriers faced in daily clinical practice in the assessment and management of major depressive disorder and how the use of trazodone could address some unmet needs. The objective of the expert meetings and the present document was to increase knowledge of particular areas of treatment with trazodone. Expert opinion: Evidence of the role of trazodone in patients affected by major depressive disorder with anxiety symptoms, insomnia, agitation, cognitive deficits, alcohol use disorders, physical comorbidities, and suicide risk has been identified, showing the effectiveness of trazodone in different presentations of major depressive disorder. The main characteristics of patients with depression for whom trazodone seems to be most effective have been identified, providing clinicians with information on possible uses of this drug in such population of patients.

Background: Research has extensively documented inequalities in inpatient psychiatric care provided to people of minoritized ethnic groups. Nonetheless, the role of their previous engagement with community mental health care has been little studied.Aims: We aimed at exploring whether previous clinical care can influence key domains of subsequent psychiatric inpatient care for people of ethnic minorities.Methods: We identified patients with a first hospital admission between 2016 and 2022, from a representative, highly diverse, catchment area of Northern Italy, using electronic health data of the NOMIAC study. We aimed at testing the impact of clinical care prior to admission on indicators of poor inpatient care, as identified by a participatory expert panel, that is, compulsory admission, insufficient length of stay, administration of Long-Acting Antipsychotics (LAI) during the last 7 days before discharge. Multiple regression models, predicted and counterfactual proportions and path analyses from generalized structural equations modeling were used to explore the association between belonging to ethnic minorities and these indicators.Results: Among 1,524 participants, 18% were from minoritized ethnic groups. While these were more likely to experience an involuntary admission, regardless of previous care received, they were offered appropriate length of stay if had previous engagement with community mental health care. Both belonging to ethnic minorities and mental health care prior-to-admission were independently associated with early LAI administration.Conclusions: Several ethnic inequalities in inpatient care continue despite previous community mental health care provided. Future research should examine how these disparities translate into clinical outcomes. Nonetheless, there is the need to actively promote equity, improving the quality of inpatient care of minoritized ethnic groups.

Introduction: Schizophrenia spectrum disorders (SSDs) are associated with immune-inflammatory activation. Recently, complete blood count (CBC)-based inflammation indexes such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), and the platelet-to-lymphocyte ratio (PLR) have emerged as reproducible and cost-effective inflammation markers in mental disorders. In this study, we aimed at investigating the relationship of NLR, MLR, and PLR with symptom severity in people with SSDs, testing interactions with relevant clinical variables. Methods: We included inpatients with SSDs aged 18-65 consecutively hospitalized from May 2020 to March 2024. Socio-demographic and clinical data were recorded. CBC-based ratios were estimated from routinely collected blood samples. Structural equation modelling (SEM) was performed to test relationships involving symptom severity constructs and CBC-based ratios, accounting for substance use disorder, antipsychotic treatment, and obesity. Results: Two hundred sixty-six participants met inclusion criteria. The SEM analysis uncovered a significant relationship of MLR with positive (coeff.: 0.19, p=0.048) and negative (coeff.: 0.27, p=0.004) symptoms, also showing a significant link of substance use disorder and antipsychotic treatment with symptom severity as well as of antipsychotic treatment with obesity. Conclusions: Notwithstanding the cross-sectional design and the somewhat limited sample representativeness, this study showed a significant relationship between the MLR - but not the NLR or the PLR - and the severity of both positive and negative symptoms, testing at the same time the interactions with other clinical variables. Considering the insufficiency and inconsistency of data in this field, further research is needed to validate our findings and elucidate the underlying mechanisms driving the observed relationships between the MLR and SSD symptoms.

Preliminary evidence shows that the kynurenine pathway (KP) may be altered in attention-deficit/hyperactivity disorder (ADHD). We thus conducted a systematic review and meta-analysis exploring the peripheral blood concentrations of tryptophan catabolites (TRYCATs) in people with ADHD. We searched the main electronic databases up to 7th December 2023. Standardised mean differences (SMDs) with 95% confidence intervals (95%CIs) were used to compare TRYCAT concentrations between participants with ADHD and healthy controls (HCs). We included eight studies. Random-effects meta-analyses found higher kynurenine (SMD = 0.56; 95%CI: 0.04 to 1.08; p = 0.033; I2 = 90.3%) and lower kynurenic acid (SMD = −0.33; 95%CI: −0.49 to −0.17; p < 0.001; I2 = 0%) concentrations in people with ADHD compared to HCs. Additional analyses on drug-free children with ADHD showed higher tryptophan (SMD = 0.31; 95%CI: 0.11 to 0.50; p = 0.002; I2 = 0%) and kynurenine (SMD = 0.74; 95%CI: 0.30 to 1.17; p < 0.001; I2 = 76.5%), as well as lower kynurenic acid (SMD = −0.37; 95%CI: −0.59 to −0.15; p < 0.001; I2 = 0%) blood levels, as compared to HCs. Despite some limitations, our work provides preliminary evidence on KP alterations in ADHD that may suggest decreased neuroprotection. Further research is needed to clarify the role of the KP in ADHD.

Objective. Most people with major depressive episodes meet criteria for the anxiety distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feeling of tension, restlessness, and difficulty concentrating, and fear that something awful may happen. This cross-sectional study was aimed at identifying clinical correlates of AD in people with unipolar or bipolar depression. Methods. Inpatients with a current major depressive episode were included. Data on sociodemographic and clinical variables were collected. The SCID-5 was used to diagnose depressive episodes and relevant specifiers. The Montgomery-Åsberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) were used to assess the severity of depression and symptoms of the opposite polarity (manic symptoms), respectively. Multiple logistic regression analyses were carried out to identify clinical correlates of AD. Results. We included 206 people (mean age: 48.4±18.6 yrs.; males: 38.8%) admitted for a major depressive episode (155 with major depressive disorder and 51 with bipolar disorder). Around two thirds of the sample (N=137; 66.5%) had AD. Multiple logistic regression models showed that AD was associated with mixed features, higher YMRS scores, psychotic features, and a diagnosis of major depressive disorder (p < 0.05). There were no other clinical variables associated with AD. Conclusion. Despite some limitations, including the cross-sectional design and the inpatient setting, our study shows that AD is likely to be associated with mixed and psychotic features, as well as with unipolar depression. The identification of these clinical domains may be helpful for clinicians to better contextualize AD in the context of major depressive episodes.

This is an overview of recent advances on predominant polarity conceptualization in bipolar disorder (BD). Current evidence on its operationalized definitions, possible contextualization within the affective spectrum, along with its epidemiological impact, and treatment implications, are summarized. Predominant polarity identifies three subgroups of patients with BD according to their mood recurrencies: (i) those with depressive or (ii) manic predominance as well as (iii) patients without any preponderance ('nuclear' type). A predominant polarity can be identified in approximately half of patients, with similar rates for depressive and manic predominance. Different factors may influence the predominant polarity, including affective temperaments. More generally, affective disorders should be considered as existing on a spectrum ranging from depressive to manic features, also accounting for disorders with 'ultrapredominant' polarity, i.e., unipolar depression and mania. While mixed findings emerge on its utility in clinical practice, it is likely that the construct of predominant polarity, in place of conventional differentiation between BD-I and BD-II, may be useful to clarify the natural history of the disorder and select the most appropriate interventions. The conceptualization of predominant polarity seems to reconcile previous theoretical views of both BD and affective spectrum into a novel perspective. It may provide useful information to clinicians for the early identification of possible trajectories of BD and thus guide them when selecting interventions for maintenance treatment. However, further research is needed to clarify the specific role of predominant polarity as a key determinant of BD course, outcome, and treatment response.

Objective: Substance Use Disorders (SUD) are common in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). Although predictors of SUD in this population are relevant for prevention and treatment, they need further clarification. Affective temperaments potentially associated with SUD in adult ADHD patients were explored. Methods: ADHD patients with and without SUD were compared for sociodemographic, clinical, and psychological characteristics through: Adult ADHD Self-Report Scale; Wender Utah Rating Scale; Temperament Evaluation Memphis for Pisa, Paris, and San Diego-Autoquestionnaire. Logistic regression investigated factors associated with SUD. Results: We included one-hundred and thirty-six ADHD patients with (n = 51, 37.5 %) and without SUD (n = 85, 62.5 %). The presence of SUD was associated with irritable temperament (p = 0.009), as well as more frequent school failure (p = 0.038), legal problems (p = 0.039), and lifetime suicide attempts (p = 0.014). Limitations: The cross-sectional design, the relatively small sample size, and the use of self-administered questionnaires. Conclusions: This study confirms the greater overall severity of adult ADHD-SUD compared with ADHD-only patients and suggests the potential role of irritable temperament as a predictor of substance-related problems.

The antidepressant effects of ketamine and esketamine are well-documented. Nonetheless, most of the underlying molecular mechanisms have to be uncovered yet. In the last decade, metabolomics has emerged as a useful means to investigate the metabolic phenotype associated with depression as well as changes induced by antidepressant treatments. This mini-review aims at summarizing the main findings from preclinical and clinical studies that used metabolomics to investigate the metabolic effects of subanesthetic, antidepressant doses of ketamine and esketamine and their relationship with clinical response. Both animal and human studies report alterations in several metabolic pathways - including the tricarboxylic acid cycle, glycolysis, the pentose phosphate pathway, lipid metabolism, amino acid metabolism, the kynurenine pathway, and the urea cycle - following the administration of ketamine or its enantiomers. Although more research is needed to clarify commonalities and differences in molecular mechanisms of action between the racemic compound and its enantiomers, these findings comprehensively support an influence of ketamine and esketamine on mitochondrial and cellular energy production, membrane homeostasis, neurotransmission, and signaling. Metabolomics may thus represent a promising strategy to clarify molecular mechanisms underlying treatment-resistant depression and related markers of clinical response to ketamine and esketamine. This body of preclinical and clinical evidence, if further substantiated, has the potential to guide clinicians towards personalized approaches, contributing to new paradigms in the clinical management of depression.

OBJECTIVE: Evidence on the relationship between depression and clinical dimensions of schizophrenia remains limited. This cross-sectional study investigated the association between depression and Positive and Negative Syndrome Scale (PANSS) dimensions in people with schizophrenia spectrum disorders. METHODS: Trained assessors administered the PANSS to measure symptoms of schizophrenia and the Calgary Depression Scale for Schizophrenia to measure depression. The association of depression with overall PANSS score and related dimensions was investigated in multiple logistic regression analyses. RESULTS: We included 231 inpatients with schizophrenia spectrum disorders (mean age: 42.4 (SD: 12.9) years; men: 58.9%; mean overall PANSS score: 82.5 (SD: 20.1); drug-free or naïve: 39.3%), including 78 (33.8%) with clinically significant depressive symptoms. Depression was associated with higher overall (regression coefficient, SE: 0.029, 0.008; p < 0.001) and general psychopathology (regression coefficient, SE: 0.118, 0.023; p < 0.001) PANSS scores. We found an inverse relationship between depression and positive symptoms (regression coefficient, SE: -0.088, 0.028; p = 0.002). No association between depression and negative symptoms was found. CONCLUSION: Despite some limitations, our study shows that people affected by schizophrenia spectrum disorders with depression are likely to show more overall and general psychopathology symptoms but lower positive symptoms. Additional studies are needed to explore the generalizability of our findings.

Background: Organisational and individual barriers often prevent university students from seeking mental health support. Digital technologies are recognised as effective in managing psychological distress and as a source of health-related information, thus representing useful options to address mental health needs in terms of accessibility and cost-effectiveness. However, university students' experiences and perspectives towards such interventions are little known. Objectives: We thus aimed to expand the existing base of scientific knowledge, focusing on this special population. Methods: Data were from the qualitative component of “the CAMPUS study”, longitudinally assessing the mental health of students at the University of Milano-Bicocca (Italy) and the University of Surrey (UK). We conducted in-depth interviews and thematically analysed the transcripts using the framework approach. Results: An explanatory model was derived from five themes identified across 33 interviews (15 for Italy, 18 for the UK). Students perceived that social media, apps, and podcasts could deliver relevant mental health content, ranging from primary to tertiary prevention. Wide availability and anonymity were perceived as advantages that make tools suitable for preventive interventions, to reduce mental health stigma, and as an extension of standard treatment. These goals can be hindered by disadvantages, namely lower efficacy compared to face-to-face contact, lack of personalisation, and problematic engagement. Individual and cultural specificities might influence awareness and perspectives on the use of digital technologies for mental health support. Conclusion: Although considering some specific features, digital tools could be a useful instrument to support the mental health needs of students. Since personal contact remains crucial, digital tools should be integrated with face-to-face interventions through a multi-modal approach.

Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depress

Background: Nonpharmacological approaches are recommended as first-line treatment for the neuropsychiatric symptoms of persons living with dementia. Tailored Activity Program is a non-pharmacological approach which has shown to reduce neuropsychiatric symptoms and functional dependence of persons living with dementia at the community, as well as caregiver’s distress. The aim of the study is to assess the feasibility of a project in which the Tailored Activity Program is delivered partially at an acute hospital ward and partially at the patient's home. Material and Methods: The study is aimed at enrolling 50 dyads (patients/caregivers) from the memory clinic, acute geriatric ward, or short-stay emergency department at the IRCCS San Gerardo dei Tintori, Monza (Italy). Inclusion criteria are: the patient’s clinical diagnosis of dementia, clinically detectable neuropsychiatric symptoms (Neuro Psychiatric Inventory, NPI score >6 in at least one item), the ability to participate in activities of daily living (Katz’s index ≥ 2), the presence of a caregiver (aged ≥ 21 years; minimum 4 hours of daily care), and the willingness of the dyad patient/caregiver to participate in the project. Treatment is delivered both i) in hospital (2 sessions) and ii) at home (6 sessions), including occupational therapy, telemedicine and nursing care provided once a week. The following variables are measured: Neuro Psychiatric Inventory, Time Up and Go Test, Katz’s Index and the level of caregiver’s sense of competence with the Sense of Competence Questionnaire. Data are collected both at baseline, at the end of the treatment, with a follow-up scheduled at 4 months after enrollment. Primary outcome measure is the dyad's retention rate at 4-month follow-up. Secondary outcomes are the reduction in the patient’s frequency and severity of NPS; the improvement in the patient’s Time Up and Go Test score; the improvement in the patient's levels of autonomy and participation in activities of daily

Introduction: The role of anterior pituitary hormones – i.e., adrenocorticotropic hormone (ACTH), luteinizing and follicle stimulating hormones (LH and FSH), growth hormone (GH), prolactin (PRL), and thyroid-stimulating hormone (TSH) – in early schizophrenia and psychoses unclear. We thus performed a systematic review and meta-analysis on the blood concentrations of ACTH, LH and FSH, GH, PRL, and TSH in drug-naïve people with first-episode psychosis (FEP) as compared with healthy controls. Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed until September 2022. Data quality was appraised. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Between-study heterogeneity was estimated using the I2 statistic. Sensitivity and meta-regression analyses were performed. Results: Twenty-six studies were included. Drug-naïve people with FEP, compared to healthy subjects, had higher blood concentrations of ACTH (k = 7; N = 548; SMD = 0.62; 95%CI: 0.29 to 0.94; p < 0.001; I2 = 60.9%) and PRL (k = 17; N = 1757; SMD = 0.85; 95%CI: 0.56 to 1.14; p < 0.001; I2 = 85.5%) as well as lower levels of TSH (k = 6; N = 677; SMD = –0.34; 95%CI: –0.54 to –0.14; p = 0.001; I2 = 29.1%). Meta-regressions did not show any moderating effect of age (p = 0.78), sex (p = 0.21), or symptom severity (p = 0.87) on PRL concentrations in drug-naïve FEP. Available data were not sufficient to perform meta-analyses on FSH, LH, and GH. Conclusions: Drug-naïve people with FEP have altered ACTH, PRL, and TSH blood concentrations, supporting the hypothesis that an abnormal anterior pituitary hormone secretion may be involved in the onset of schizophrenia and psychoses. Further research is needed to elucidate the role of pituitary hormones in FEP.

Religiosity may reduce the risk of substance use in adults and young people. However, religiosity is a complex construct, variously defined and assessed. We explored the role of different religious components: intrinsic (subjective), extrinsic-personal (service attendance) and extrinsic-social (church-based social activities) in deterring cannabis use among adolescents. Combining several years (2015–2019) of NSDUH data on 68,263 adolescents between 12 and 17 years, a structural equation modelling (SEM) approach was used to evaluate pathways from intrinsic and extrinsic components of religiosity to cannabis use. We analyzed the role of several covariates, including comorbid depression and secular volunteering activities. About 15% of participants said they had used cannabis at some level in the previous year. Some degree of intrinsic and of extrinsic-personal religiosity was reported by 66% and 25% of the sample. 57% were committed to at least one faith-based activity, while 74% reported participation in non-faith-based community activities. The SEM regression model -controlling for putative confounders- showed that both intrinsic and extrinsic-personal religious components reduced the likelihood of cannabis use (Cannabis use coeff.: −0.065, p = 0.001; coeff.: −0.176, p < 0.001, respectively). However, the extrinsic-social component had no effect on refraining from cannabis use, despite involvement in non-faith based volunteering activities was protectively associated. Support for secular volunteering programs may be a cost-effective mechanism for reducing cannabis use. Moreover, whilst promoting religiosity is beyond the scope of any preventive programs, religious practices should be considered relevant protective factors, deserving consideration and support in terms of public health.

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann–Whitney U test, Kaplan–Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis.

The brain-derived neurotrophic factor (BDNF) has received considerable attention as a potential biomarker of major depressive disorder (MDD) and antidepressant response. We conducted an overview of meta-analyses investigating the relationship of BDNF with MDD, related clinical features, and antidepressant treatment. Based on a systematic screening on main electronic databases, 11 systematic reviews with meta-analyses were included. Available evidence suggests that people with MDD have peripheral and central BDNF levels lower than non-depressed individuals. A negative correlation between blood BDNF and symptom severity emerged, while no association with suicidality was detected. Moreover, an increase in blood BDNF levels after antidepressant treatment, proportional to symptom improvement, was reported. BDNF levels seem to be increased in both treatment responders and remitters, remaining stable in non-responders. Conversely, no variations of BDNF concentrations after non-pharmacological interventions (electroconvulsive therapy, repetitive transcranial magnetic stimulation, and physical activity) were found. The findings of this overview appear consistent with the neurotrophic hypothesis of depression, suggesting that BDNF may play a role in both MDD pathophysiology and pharmacological treatment response.

University students are particularly vulnerable to mental health issues, with anxiety and depression identified as the most common conditions. During the COVID-19 pandemic, social distancing, self-isolation, and difficulties linked to online teaching and learning have increased their burden of anxiety and depressive symptoms. Thus, the urgent need to intervene in favour of these vulnerable subjects, together with the difficulties in delivering in-person interventions because of lockdowns and restrictions, has led to prioritize digital mental health strategies. This study aimed at systematically reviewing the existing literature on digital mental health interventions targeting anxiety and depressive symptoms in university students during the COVID-19 emergency. Systematic searches of Medline, Embase, and PsycInfo databases identified eight randomized controlled trials. Regarding anxiety symptoms, digitally delivered cognitive behavioural therapy, dialectical behaviour therapy, and mind-body practice techniques emerged as valid strategies, while digital positive psychology and mindfulness-based interventions showed mixed results. On the other hand, digitally delivered dialectical behaviour therapy and positive psychology interventions have shown some efficacy in reducing depressive symptoms. Overall, the available literature, albeit of low quality, seems to support the role of digital interventions in promoting the mental health of university students during the COVID-19 pandemic.

Objective: Attention deficit hyperactivity disorder is a frequent comorbid condition in adults with bipolar disorder. We performed a meta-analysis aimed at assessing sociodemographic and clinical correlates of attention deficit hyperactivity disorder in bipolar disorder. Method: We searched main electronic databases up to June 2021. Random-effects meta-analyses, with relevant meta-regression and quality-based sensitivity analyses, were carried out to estimate the association between attention deficit hyperactivity disorder and putative correlates, grading the quality of evidence. Results: We included 43 studies, based on 38 independent samples. Attention deficit hyperactivity disorder participants were more likely to be males (odds ratio = 1.46; p < 0.001) and unemployed (odds ratio = 1.45; p = 0.045), and less likely to be married (odds ratio = 0.62; p = 0.014). They had an earlier onset of bipolar disorder (standardized mean difference = −0.36; p < 0.001); more mood episodes (standardized mean difference = 0.35; p = 0.007), particularly depressive (standardized mean difference = 0.30; p = 0.011) and mixed (standardized mean difference = 0.30; p = 0.031) ones; higher odds of using antidepressants (odds ratio = 1.80; p = 0.024) and attempted suicides (odds ratio = 1.83; p < 0.001) and lower odds of psychotic features (odds ratio = 0.63; p = 0.010). Moreover, they were more likely to have generalized anxiety disorder (odds ratio = 1.50; p = 0.019), panic disorder (odds ratio = 1.89; p < 0.001), social phobia (odds ratio = 1.61; p = 0.017), eating disorders (odds ratio = 1.91; p = 0.007), antisocial personality disorder (odds ratio = 3.59; p = 0.004) and substance (odds ratio = 2.29; p < 0.001) or alcohol (odds ratio = 2.28; p < 0.001) use disorders. Quality of the evidence was generally low or very low for the majority of correlates, except for bipolar disorder onset and alcohol/substance use disorders (high), and suicide attempts (moderate). Conclu

Introduction: Pteridines, such as neopterin, biopterin, and tetrahydrobiopterin (BH4), may be involved in depression pathophysiology owing to their links to immune-inflammatory response, oxidative and nitrosative stress, and monoaminergic transmission. Nonetheless, studies assessing pteridines in depression are inconsistent. We conducted a systematic review and meta-analysis of observational studies comparing blood pteridine concentrations between subjects with depression and healthy controls (HCs). Methods: We searched Embase, MEDLINE, and PsycInfo for articles indexed through November 2021. Study quality was appraised, evaluating age and gender comparability between groups, sample representativeness, and methods to assess depression. Random-effects meta-analyses were carried out, generating pooled standardized mean differences (SMDs). Heterogeneity across studies was estimated using the I2 statistic. Results: Twenty-four studies, involving 3075 subjects, were included. Individuals with depression showed blood neopterin concentrations higher than HCs (k = 19; SMD = 0.36; p < 0.001) with moderate heterogeneity across studies (I2 = 58.2%). No moderating role of age, gender, or type of blood sample was found. Sensitivity analyses showed no impact of inconsistency and quality of studies on findings. Neopterin concentrations were higher among individuals with major depressive disorder compared to HCs (SMD = 0.44; p < 0.001). This held true also when considering only drug-free subjects (SMD = 0.68; p = 0.003). No differences in biopterin concentrations were found between subjects with depression and HCs (k = 5; SMD = –0.35; p = 0.086), though this result was limited by inconsistency of findings (I2 = 77.9%) and quality of studies. Finally, no sufficient data were available for a meta-analysis on BH4. Conclusions: As a whole, our work partly supports the hypothesis of an imbalance of pteridine metabolism in depression.

Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.

Introduction: New digital technologies can become a tool for welcoming the patient through the artistic dimension. Cancer patients, in particular, need support that accompanies and supports them throughout their treatment. Materials and methods: The Art4ART project consist in the structural proposal to cancer patients of a web-based digital platform containing several forms of art as video-entertainments; a multimedia immersive room; an art-based welcoming of the patients with several original paintings; an environment with a peacefulness vertical garden; a reconceptualization of the chemotherapy-infusion seats. Data regarding patients’ preference and choices will be stored and analysed also using artificial intelligence (AI) algorithm to measure and predict impact indicators regarding clinical outcomes (survival and toxicity), psychological indicators. Moreover, the same digital platform will contribute to a better organization of the activities. Discussion: Through the systematic acquisition of patient preferences and through integration with other clinical parameters, it will be possible to measure the clinical, psychological, organisational, and social impact of the newly implemented Art4ART project. The use of digital technology leads us to apply the reversal of viewpoint from therapeutic acts to patient-centred care.

In the last four decades, mental health services for people with Severe Mental Illness (SMI) have seen asylums replaced by a balanced model of Community Mental Healthcare (CMH). Innovative approaches and strategies in the field of CMH have been extensively researched. However, this research has been hampered by issues limiting their capacity to inform clinicians and policymakers. We conducted an overview of meta-analyses of the effectiveness of innovative CMH models focussing on clinical and psychosocial outcomes in comparisons with standard care in adults with SMI. Based on the 12 eligible studies, we appraised, synthesised and graded the resulting evidence. There was moderate quality evidence that case management, Early Intervention Services (EIS) and caregiver-directed interventions were superior to standard care in reducing hospital admission. In relation to psychosocial outcomes, EIS showed high quality evidence of a small effect on global functioning. There was moderate quality evidence for a similar effect of Intensive Case Management, and for a large effect of family intervention. For quality of life, both EIS and self-management education had a small effect, with moderate quality. The level of research about effective CMH models is therefore substantial. However, several gaps related to innovative CMH not yet covered in meta‐analytic synthesis, need to be filled.

In this prospective study, we assessed the effectiveness and acceptability of paliperidone palmitate 1-month (PP1M) and aripiprazole monohydrate (AM) over 1-year follow-up. We included 195 subjects (117 treated with PP1M and 78 with AM) with schizophrenia spectrum disorders from real-world settings. We estimated no differences in hospitalization (Odds Ratio=1.59; p = 0.12), symptoms improvement (p = 0.90 adjusted for baseline severity), and discontinuation (Hazard Ratio=0.72; p = 0.20) at study endpoint. Although current evidence suggests the possible superiority of AM over PP1M, our findings showed comparable effectiveness between these drugs. Additional studies in real-world settings with direct comparisons between these two LAIs are needed.

Background: The aim of this study was to evaluate the effectiveness of positron emission tomography/computed tomography with [18 F]-fludeoxyglucose (FDG-PET/CT) and radiomics analysis in detecting differences between the native aorta and the abdominal aortic allograft after the total eradication of infection in patients undergoing infected graft removal and in situ reconstruction with cryopreserved allografts. Methods: Between January 2008 and December 2018, 56 vascular reconstructions with allografts have been performed at our department. The present series included 12 patients undergoing abdominal aortic in situ reconstruction with cryopreserved allografts. During the follow-up, all patients underwent a total-body [18 F]FDG PET/CT with subsequent radiomics analysis. In all patients, a comparative analysis between the data extracted from native aorta and cryopreserved graft for each patient was performed. Results: All patients were male with a mean age of 72.8 years (range 63–84). Mean duration of follow-up was 51.3 months (range 3–120). During the follow-up, 2 patients (16.7%) needed a redo allograft-related surgical intervention. Overall, the rate of allograft dilatation was 33.3%. No patient had a redo infection during the follow-up. Radiomics analysis showed a different signature of implanted allograft and native aorta. Comparative analysis between the native aortas and cryopreserved allografts (dilated or not) showed several statistical differences for many texture features. Conclusions: The higher metabolic activity of allografts could indicate a state of immune-mediated degeneration. This theory should be proven with prospective, multicentric studies with larger sample sizes.

Purpose of Review: Cardiovascular infections are serious disease associated with high morbidity and mortality. Their diagnosis is challenging, requiring a proper management for a prompt recognition of the clinical manifestations, and a multidisciplinary approach involving cardiologists, cardiothoracic surgeons, infectious diseases specialist, imagers, and microbiologists. Imaging plays a central role in the diagnostic workout, including molecular imaging techniques. In this setting, two different strategies might be used to image infections: the first is based on the use of agents targeting the microorganism responsible for the infection. Alternatively, we can target the components of the pathophysiological changes of the inflammatory process and/or the host response to the infectious pathogen can be considered. Understanding the strength and limitations of each strategy is crucial to select the most appropriate imaging tool. Recent Findings: Currently, multislice computed tomography (MSCT) and nuclear imaging (18F-fluorodeoxyglucose positron emission tomography/computed tomography, and leucocyte scintigraphy) are part of the diagnostic strategies. The main role of nuclear medicine imaging (PET/CT and SPECT/CT) is the confirmation of valve/CIED involvement and/or associated perivalvular infection and the detection of distant septic embolism. Proper patients’ preparation, imaging acquisition, and reconstruction as well as imaging reading are crucial to maximize the diagnostic information. Summary: In this manuscript, we described the use of molecular imaging techniques, in particular WBC imaging, in patients with infective endocarditis, cardiovascular implantable electronic device infections, and infections of composite aortic graft, underlying the strength and limitations of such approached as compared to the other imaging modalities.

Introduction: Studies have shown that the Ki-67 index is a valuable biomarker for the diagnosis, and classification of gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs). We re-evaluated the expression of Ki-67 based on the intensity of the stain, basing our hypothesis on the fact that the Ki-67 protein is continuously degraded. Background: The aim was to evaluate whether a new scoring method would be more effective in classifying NETs by reducing staining heterogeneity. Methods: Patients with GEP-NET (n = 87) were analyzed. The classification difference between the two methods was determined. Results: The classification changed significantly when the Ki-67 semiquantal index was used. The percentage of G1 patients increased from 18.4% to 60.9%, while the G2 patients decreased from 66.7% to 29.9% and the G3 patients also decreased from 14.9% to 9.2%. Moreover, it was found that the traditional Ki-67 was not significantly related to the overall survival (OS), whereas the semiquantal Ki-67 was significantly related to the OS. Conclusions: The new quantification was a better predictor of OS and of tumor classification. Therefore, it could be used both as a marker of proliferation and as a tool to map tumor dynamics that can influence the diagnosis and guide the choice of therapy.

Aim: to exploit tissue-specific interactions among thymic epithelial tumor (TETs) cells and extra-domain B fibronectin (ED-B FN). Material and methods: The stromal pattern of ED-B FN expression was investigated through tumor specimen collection and molecular profiling in 11 patients with recurrent TETs enrolled in prospective theragnostic phase I/II trials with Radretumab, an ED-B FN specific recombinant human antibody. Radretumab radioimmunotherapy (R-RIT) was offered to patients who exhibited the target expression. Experiments included immunochemical analysis (ICH), cell cultures, immunophenotypic analysis, Western blot, slot-blot assay, and quantitative RT-PCR of two primary thymoma cultures we obtained from patients’ samples and in the Ty82 cell line. Results: The in vivo scintigraphic demonstration of ED-B FN expression resulted in R-RIT eligibility in 8/11 patients, of which seven were treated. The best observed response was disease stabilization (n = 5/7) with a duration of 4.3 months (range 3–5 months). IHC data confirmed high ED-B FN expression in the peripherical microenvironment rather than in the center of the tumor, which was more abundant in B3 thymomas. Further, there was a predominant expression of ED-B FN by the stromal cells of the thymoma microenvironment rather than the epithelial cells. Conclusions: Our data support the hypothesis that thymomas induce stromal cells to shift FN production to the ED-B subtype, likely representing a favorable hallmark for tumor progression and metastasis. Collectively, results derived from clinical experience and molecular insights of the in vitro experiments suggested that R-RIT inefficacy is unlikely related to low target expression in TET, being the mechanism of R-RIT resistance eventually related to patients’ susceptibility (i.e., inherent characteristics), the pattern expression of the target (i.e., at periphery), the biological characteristics of the tumor (i.e., aggressive and resistant phenotypes), and/or t

FAP-targeted radiopharmaceuticals represent a breakthrough in cancer imaging and a viable option for therapeutic applications. OncoFAP is an ultra-high-affinity ligand of FAP with a dissociation constant of 680 pM. OncoFAP has been recently discovered and clinically validated for PET imaging procedures in patients with solid malignancies. While more and more clinical validation is becoming available, the need for scalable and robust procedures for the preparation of this new class of radiopharmaceuticals continues to increase. In this article, we present the development of automated radiolabeling procedures for the preparation of OncoFAP-based radiopharmaceuticals for cancer imaging and therapy. A new series of [68Ga]Ga-OncoFAP, [177Lu]Lu-OncoFAP and [18F]AlF-OncoFAP was produced with high radiochemical yields. Chemical and biochemical characterization after radiolabeling confirmed its excellent stability, retention of high affinity for FAP and absence of radiolysis by-products. The in vivo biodistribution of [18F]AlF-NOTA-OncoFAP, a candidate for PET imaging procedures in patients, was assessed in mice bearing FAP-positive solid tumors. The product showed rapid accumulation in solid tumors, with an average of 6.6% ID/g one hour after systemic administration and excellent tumor-to-healthy organs ratio. We have developed simple, quick, safe and robust synthetic procedures for the preparation of theranostic OncoFAP-compounds based on Gallium-68, Lutetium-177 and Fluorine-18 using the commercially available FASTlab synthesis module.

Molecular targeting requires assessing several factors that come into play such as the location of the target, the choice of radionuclide, the inertness of the bifunctional chelate and stability of the covalently bound halogens, matching the residence time in the tumor with the physical half-life of the radionuclide, the scale and scope of the disease, and the absorbed dose sensitivity of the targeted tumor compared to normal tissue. The principles of molecular targeting are well established, but a paradigm shift from designing a medium-affinity radiotracer used to determine target density to designing a high-affinity, high-target density radioligand to maximize the target-to-nontarget ratio should increase the probability of detecting lesions smaller than the instrument resolution. Developing and validating a therapeutic radiopharmaceutical for a single target is necessary, but often not sufficient to produce a toxic event because of other mechanisms that are only partially understood. These include nontargeted effects due to radiation emitted from neighboring, targeted cells as well as bystander effects produced by the cellular processing of radiation not necessarily impinging on DNA. Both of these indirect consequences of cellular radiation could make a substantial contribution to the efficacy of targeted radionuclide therapy. These mechanisms should be exploited to optimize the efficacy of targeted radiotherapy and overcome the inefficiency of tumor control due to nonuniform distribution of radiation dose. The design approach to take advantage of the indirect consequences of cellular radiation depends heavily on further elucidation of the indirect effect. The successful combination of these two should lead to more effective nuclear radiotherapy.

Infective endocarditis is associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient's management, as early treatment improves the prognosis. Hardly diagnosed on the basis of a single symptom, sign or diagnostic test. Rather, the diagnosis requires a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data and imaging data. The application of multimodality imaging, including molecular imaging techniques has improved the sensitivity to detect IE, also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this chapter, we will describe the main epidemiological, clinical and diagnostic challenges in IE with particular regard to the role of WBC SPECT/CT. In addition, the needs of proper hybrid equipment, dedicated imaging acquisition protocols, specific expertise for imaging reading and imaging interpretations in this field are discussed, emphasizing the need of a specific reference framework within a Cardiovascular Multidisciplinary Team Approach.

Cardiovascular (CVS) infections are associated with high morbidity and mortality. Early diagnosis is crucial for adequate patient's management, as early treatment improves the prognosis. Hardly they are diagnosed on the basis of a single symptom, sign or diagnostic test, being a multidisciplinary discussion in addition to the integration of clinical signs, microbiology data and imaging data necessary in many cases. The application of multimodality imaging, including molecular imaging techniques has improved the sensitivity to detect infections involving heart valves and vessels and implanted cardiovascular devices while also allowing for early detection of septic emboli and metastatic infections before these become clinically apparent. In this chapter, we describe the role of WBC SPECT/CT and [18F] FDG PET/CT in most clinically relevant CVS infections including dedicated imaging acquisition protocols, specific imaging reading and interpretations criteria, emphasizing the need of a specific reference framework within a Cardiovascular Multidisciplinary Team Approach to select the best test or combination of tests for each specific clinical situation.

The armamentarium of approved radiopharmaceuticals for either diagnosis or therapy is at the core of the clinical practice of today's nuclear medicine. Nevertheless, both because the currently approved agents do not meet all the clinical needs for radionuclide targeting and because advancing knowledge in the pathophysiology of tissues/organs opens in turn new opportunities, investigations continue at the preclinical and clinical validation level for the development of new radiopharmaceuticals, most of which are not approved yet for commercial use. Concerning in particular the diagnostic applications of nuclear medicine to oncology, ongoing investigations in the search for tumor-targeting agents with better specificity and sensitivity are countless, possibly within the scenario of theranostics-that is, with the dual potential for imaging and for therapy, depending on the specific radionuclide employed for radiolabeling. We will focus this chapter on the most promising imaging agents labeled with single-photon-emitting radionuclides based on some of the mechanisms that are typical for tumor cells/tissues.

Leukemias are a group of acute and chronic hematological neoplasias characterized by the dissemination of cancer cells originating in the bone marrow via the bloodstream. In 2016, the estimated number of new leukemia cases was more than 110,000 in all of Europe and 47,000 in the USA. Leukemia is the cause of 4% of all cancer deaths and accounts for 3.6% of all cancers. Historically, leukemias have been divided into four major categories further classified into subtypes based on specific features of cells: acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (CML). A revised classification of myeloid/lymphoid neoplasms and leukemias has recently been published to better characterize each disease. This updated classification incorporated new scientific and clinical information to refine diagnostic criteria for previously described neoplasms and introduced newly recognized disease entities. In this chapter, the main entities of leukemia, with specific regard to imaging for diagnosis, treatment response assessment, and follow-up, will be treated according to what is reported in the clinical guidelines.

Monoclonal antibodies (MAbs) raised against cancer antigens may mediate antibody-dependent cell-mediated cytotoxicity. This form of cancer control arises from cytolysis of a target cell by effector lymphocytes, such as cytotoxic T lymphocytes or natural killer cells. However, most of these antibodies have low/moderate efficacy in the tumor control. Antibodies targeting hormone receptors expressed by cancer have shown greater tumor control compared with other cell membrane targets. Moreover, the labeling of these antibodies with a toxin can potentiate their efficacy in the tumor control. In this way, the antibody becomes an invaluable targeting vector for delivery of the toxin to the cancer cells. The toxin/antibody complex is called the immunoconjugate. Different molecules, chemicals, or radioisotopes can serve themselves as toxins; toxins may have long half-lives in the body (e.g., ricin), thus increasing the toxicity to both the cancer and normal tissues. However, the different radioisotopes (e.g., iodine-131, lutetium-177) have a wide range of half-lives and radiation decay that make them useful for different applications. Beta-emitting radioisotopes, predominantly I-131, have had only modest success in radioimmunotherapy. More recently, high linear energy transfer (LET) radiation in the form of alpha particles has been studied: alpha radiation is ideal for killing isolated cancer cells in transit in the vascular and lymphatic systems and regressing tumors by disruption of tumor capillary networks by targeting and killing tumor capillary endothelial cells. Over the past 20 years the development of alpha-immunoconjugates has enabled targeted alpha therapy (TAT) to progress from in vitro studies, through in vivo experiments, to clinical trials. The dose to normal tissues always provides a limitation to the injected dose and that received by the tumor. However, TAT can achieve cancer regression within the maximum tolerance dose for normal tissue. TAT was originally

Impaired hormonal regulation of appetite may contribute to higher cardiovascular risk in bipolar disorder (BD). We performed a systematic review and meta-analysis of studies investigating peripheral blood levels of appetite-regulating hormones in BD and controls. A total of 32 studies were included. Leptin and insulin levels were significantly elevated in patients with BD during euthymia, but not in other mood states. Greater differences in the number of male participants between patients with BD and healthy controls were associated with higher effect size estimates for the levels of insulin. There were significant positive correlations of effect size estimates for the levels of adiponectin with the percentage of individuals with type I BD and duration of BD. Our findings point to the mechanisms underlying high rates of cardiometabolic comorbidities in BD. Moreover, they suggest that investigating hormonal regulation of appetite might help to understand differences in the neurobiology of BD types.

Personalized approaches in psychiatry, albeit being extensively explored in the literature since the early 2010s [...].