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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.

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.

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.

Background: The mental health of the Italian population declined at the onset of the COVID-19 pandemic. However, nationwide population prevalence estimates may not effectively reproduce the heterogeneity in distress responses to the pandemic. In particular, contextual determinants specific to COVID-19 pandemic need to be considered. We thus aimed to explore the association between local COVID-19 mortality rates and mental health response among the general population. Methods: We capitalised on data (N = 17,628) from a large, cross-sectional, national survey, the COMET study, run between March and May 2020. While psychological distress was measured by General Health Questionnaire–12 (GHQ-12), the Depression, Anxiety and Stress Scale-21 Items (DASS-21) was used to assess relevant domains. In addition, a Covid-19 mortality ratio was built to compare single regional mortality rates to the national estimate and official statistics were used to control for other area-level determinants. Results: Adjusted ordered regression analyses showed an association between mortality ratio and moderate (OR = 1.10, 95%CI 1.03–1.18) and severe (OR = 1.11, 95%CI 1.03–1.21) DASS-21 anxiety levels. No effects of mortality ratio on GHQ-12 scores and DASS-21 depression and stress levels, uniformly high across the country, were estimated. Conclusions: Although we could not find any association between regional COVID-19 mortality ratio and depression or psychological distress, anxiety levels were significantly increased among subjects from areas with the highest mortality rates. Local mortality rate seems a meaningful driver for anxiety among the general population. Considering the potentially long-lasting scenario, local public health authorities should provide neighbouring communities with preventive interventions reducing psychological isolation and anxiety levels.

Several drugs previously tested in clinical trials and approved for different indications have been repurposed for bipolar disorder. We carried out a systematic meta-review of meta-analyses of randomized placebo-controlled trials investigating repurposed drugs as adjunctive treatments for mania and bipolar depression. We performed a critical appraisal using ‘A MeaSurement Tool to Assess systematic Reviews’ Version 2 (AMSTAR 2). We synthesized results on efficacy, tolerability, and safety, assessing evidence quality according to the ‘Grading of Recommendations, Assessment, Development and Evaluations’ (GRADE) approach. Our systematic search identified nine eligible studies investigating 12 drugs, four for mania and eight for bipolar depression. The quality of reporting was heterogeneous according to AMSTAR 2. In mania, allopurinol (for symptoms reduction and remission at 4–8 weeks) and tamoxifen (for response and symptoms reduction at 4–6 weeks) showed higher efficacy than placebo, with low and very low quality of evidence, respectively. Concerning bipolar depression, modafinil/armodafinil (for response, remission, and symptoms reduction at 6–8 weeks) and pramipexole (for response and symptoms reduction at 6 weeks) were superior to placebo, despite the low quality of evidence. Results on the efficacy of celecoxib and N-acetylcysteine were of low quality and limited to certain outcomes. Overall, the lack of evidence of high and moderate quality does not allow us to draw firm conclusions on the clinical utility of repurposed drugs as adjunctive treatments for mania and bipolar depression, highlighting the need for additional research.

This metasynthesis brings together what is known about family members’ perspectives of their relationship with social care practitioners as a starting point for developing a pan-European training resource for practitioners. Four databases were searched for qualitative literature with search terms relating to family members and social care practitioners. After the application of inclusion and exclusion criteria, 35 studies were critically appraised and were included in the metasynthesis. Three broad themes were identified through a thematic analysis of the studies’ findings: family members’ perspectives of the system; perceptions of how they were viewed by their worker; and view of their worker. The following aspects are discussed: whether partnership between family and worker is possible within a legal framework; the detrimental effects of cultural bias; and practical foundations for building trust. Recommendations are made for practical support, reflection on cultural practice and broader service provision.

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.

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.

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 current systematic review and meta-analysis aimed at exploring acute effects of intravenous (IV) ketamine, an antagonist of N-methyl-D-aspartate (NMDA), in subjects with current suicidal ideation. We included clinical trials testing a single IV dose of ketamine and assessing changes in suicidal ideation within 4 h after treatment. Meta-analyses based on random-effects models, were carried out generating pooled standardized mean differences (SMDs) between endpoint and baseline scores. Heterogeneity among studies was estimated using the I2 index. We searched main Electronic Databases, identifying five studies that met our inclusion criteria. The trials included 99 subjects treated with IV ketamine bolus or infusion. Data showed a large (SMD = −0.92; 95%CI: −1.40 to −0.44; p < 0.001) and consistent (I2 = 21.6%) decrease of suicidal ideation, with effects comparable between IV bolus and infusion ketamine. Additional analyses confirmed the efficacy of ketamine across different time points. However, relevant, emerging evidence should be considered as ‘very low’ so far. Randomized, controlled and adequately powered trials are needed.

The aim of this systematic review and meta-analysis was testing whether low versus high doses of second-generation antipsychotics (SGAs) are associated with different clinical benefits and harms for the acute treatment of bipolar depression. We included clinical trials comparing different doses of the same SGA monotherapy for bipolar depression. SGAs defined daily doses were used to define high and low doses. Clinical benefit outcomes included improvement, response and remission rates on Montgomery-Asberg Depression Rating Scale. Clinical harm outcomes included all-cause and adverse effect-related discontinuation rates. Data from seven clinical trials testing high and low doses of quetiapine (4 trials), cariprazine, lurasidone, and ziprasidone (1 trial each), showed no differences between lower and higher doses of selected SGAs on improvement, response and remission rates, without significant heterogeneity across studies (I2 = 0%). Subgroup analyses based on single SGAs confirmed the clinical benefit comparability between low and high doses. However, clinical harm favorable differences for low doses on all-cause (p = 0.01) and adverse effects-related discontinuation (p = 0.001) were found. In sum, this meta-analysis showed that, although no benefits were found in terms of symptoms improvement, response and remission rates, there were clear disadvantages in prescribing higher rather than lower doses of selected SGAs. The uniform methodological strength of studies increases confidence in our findings. These data need to be integrated with individual patient characteristics (e.g., clinical urgency and adverse effect sensitivity) to optimize management of acute bipolar depression.

Previous research has hypothesised increased uric acid levels, possibly because of an amplified purinergic metabolism and a reduced adenosine activity, in subjects with bipolar disorder. This systematic review and meta-analysis aimed at estimating if individuals with bipolar disorder had uric acid levels higher than both healthy controls and subjects with major depression (trait marker hypothesis). It also tested if uric acid levels could differ in different phases of bipolar disorder (state marker hypothesis). Meta-analyses were carried out generating pooled standardized mean differences (SMDs), using random-effects models. Heterogeneity between studies was estimated using the I2 index. Relevant sensitivity and meta-regression analyses were conducted. We searched main Electronic Databases, identifying twelve studies that met our inclusion criteria. Meta-analyses showed increased uric acid levels in individuals with bipolar disorder as compared with both healthy controls (SMD = 0.65, p < 0.001, I2 = 82.9%) and those with major depression (SMD = 0.46, p < 0.001; I2 = 68.7%). However, meta-regression analyses confirmed this association only as compared with healthy controls. Finally, though uric acid levels were higher in manic/mixed phases as compared with depressive ones (SMD = 0.34; p = 0.04, I2 = 58.8%), a sensitivity analysis did not confirm the association. In sum, our meta-analysis shows that subjects with bipolar disorder have uric acid levels higher than healthy controls. The potential role of factors that might clarify the nature of this association deserves additional research.

People with alcohol and substance use disorders (AUDs/SUDs) show worse facial emotion recognition (FER) than controls, though magnitude and potential moderators remain unknown. The aim of this meta-analysis was to estimate the association between AUDs, SUDs and FER impairment. Electronic databases were searched through April 2015. Pooled analyses were based on standardized mean differences between index and control groups with 95% confidence intervals, weighting each study with random effects inverse variance models. Risk of publication bias and role of potential moderators, including task type, were explored. Nineteen of 70 studies assessed for eligibility met the inclusion criteria, comprising 1352 individuals, of whom 714 (53%) had AUDs or SUDs. The association between substance related disorders and FER performance showed an effect size of -0.67 (-0.95, -0.39), and -0.65 (-0.93, -0.37) for AUDs and SUDs, respectively. There was no publication bias and subgroup and sensitivity analyses based on potential moderators confirmed core results. Future longitudinal research should confirm these findings, clarifying the role of specific clinical issues of AUDs and SUDs.

People with psychotic disorders, including schizophrenia (SCZ), schizoaffective disorder (SD), or other non-affective psychoses (ONAP), have a higher risk of metabolic syndrome (MetS) than general population. However, previous meta-analyses failed to explore if people with SD are more likely to suffer from MetS than SCZ and ONAP.We carried out a systematic review and meta-analysis comparing rates of MetS in SD with those in SCZ or ONAP. We searched main electronic databases for relevant articles published up to January 2015, and for unpublished data, contacting corresponding authors, to minimize selective reporting bias. Odds ratios (ORs) based on random effects models, with 95% confidence intervals (CIs), and heterogeneity (I2), were estimated. We performed leave-one-out, quality-based, and subgroups analyses to check findings validity. Testing for publication bias, Egger's test estimates were reported.We included 7616 individuals (1632 with SD and 5984 with SCZ/ONAP) from 30 independent samples. SD, as compared with SCZ/ONAP, had a random-effect pooled OR (95%CI) for MetS of 1.41 (1.23-1.61; p<0.001; I2=5%). No risk of publication bias was found (p=0.85). Leave-one-out, sensitivity, and subgroups analyses confirmed the association.To our knowledge, this is the first meta-analysis comparing MetS comorbidity between individuals with SD and those with SCZ or ONAP. SD subjects are more likely to suffer from MetS, with consistent findings across the studies included. However, the role of explanatory factors of this association, and the relative contribution of MetS subcomponents, deserve further research.

Background: People with schizophrenia are more likely than general population to suffer from metabolic abnormalities, with second-generation antipsychotics (SGAs) increasing the risk. Low plasma adiponectin levels may lead to metabolic dysregulations but evidence in people with schizophrenia, especially for the role of SGAs, is still inconclusive. Objective: To compare plasma adiponectin levels between people with schizophrenia and healthy controls, and to estimate the relative effect of schizophrenia and SGAs on adiponectin. Methods: We performed a systematic review and meta-analysis of observational studies published up to 13 June 2014 in main electronic databases. Pooled standardized mean differences (SMDs) between index and control groups were generated. Appropriate subanalyses and additional subgroup analyses were carried out. Results: Data from 2735 individuals, 1013 with and 1722 without schizophrenia, respectively, were analysed. Schizophrenia was not associated with lower adiponectin levels (SMD of -0.28, 95%CI: -0.59, 0.04; p=. 0.09). However, individuals with schizophrenia taking SGAs had plasma levels significantly lower than controls (. p=. 0.002), which was not the case of drug free/drug naïve subjects (. p=. 0.52). As regards single antipsychotic drugs clozapine (. p<. 0.001) and olanzapine (. p=. 0.04) - but not risperidone (. p=. 0.88) - were associated with adiponectin levels lower than controls. Conclusions: People with schizophrenia per se may not have levels of adiponectin lower than controls, though treatment with SGAs is associated with this metabolic abnormality. This bears clinical significance because of hypoadiponectinemia involvement in cardiovascular diseases, even if mechanisms whereby SGAs affect adiponectin remain unexplained. Longitudinal studies evaluating long-term effects of SGAs on adiponectin are needed.

Introduction: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) has made several changes to criteria for alcohol use disorder (AUD). The objective of this systematic review is to assess if new DSM-5 diagnostic criteria will increase the prevalence rates of AUD in clinical and non-clinical samples as compared with DSM-IV criteria. Methods: We searched PubMed, Scopus, and PsycINFO (via ProQuest) electronic databases, with no language restrictions. We included studies with data available on both DSM-IV (and DSM-IV-TR) and DSM-5 AUD in samples of adults, estimating from each study an expected increase in prevalence rates with relevant 95% confidence intervals (CIs). Results: Twelve studies were included in this review. Seven studies showed an increase, two no substantial difference, and three a decrease in AUD prevalence according to DSM-5 diagnostic criteria, with differences in rates (95% CIs) varying between -. 12.4% (-. 27.4 to +. 5.6%) and +. 61.3% (+. 46.7 to +. 77.3%). Additional analyses provided confirmatory results. Conclusions: DSM-5 diagnostic criteria seem to inflate prevalence rates of AUD as compared with DSM-IV. The increasing likelihood of a DSM-5 AUD diagnosis may be explained by the amount of DSM-IV 'diagnostic orphans' which are more prevalent than DSM-IV single-criterion alcohol abuse individuals. Further research should be aimed to study if similar trends are detectable also for other substance use disorders that experienced similar changes in DSM-5 diagnostic criteria.