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The serotonin hypothesis of depression is still influential. We aimed to synthesise and evaluate evidence on whether depression is associated with lowered serotonin concentration or activity in a systematic umbrella review of the principal relevant areas of research. PubMed, EMBASE and PsycINFO were searched using terms appropriate to each area of research, from their inception until December 2020. Systematic reviews, meta-analyses and large data-set analyses in the following areas were identified: serotonin and serotonin metabolite, 5-HIAA, concentrations in body fluids; serotonin 5-HT 1A receptor binding; serotonin transporter (SERT) levels measured by imaging or at post-mortem; tryptophan depletion studies; SERT gene associations and SERT gene-environment interactions. Studies of depression associated with physical conditions and specific subtypes of depression (e.g. bipolar depression) were excluded. Two independent reviewers extracted the data and assessed the quality of included studies using the AMSTAR-2, an adapted AMSTAR-2, or the STREGA for a large genetic study. The certainty of study results was assessed using a modified version of the GRADE. We did not synthesise results of individual meta-analyses because they included overlapping studies. The review was registered with PROSPERO (CRD42020207203). 17 studies were included: 12 systematic reviews and meta-analyses, 1 collaborative meta-analysis, 1 meta-analysis of large cohort studies, 1 systematic review and narrative synthesis, 1 genetic association study and 1 umbrella review. Quality of reviews was variable with some genetic studies of high quality. Two meta-analyses of overlapping studies examining the serotonin metabolite, 5-HIAA, showed no association with depression (largest n  = 1002). One meta-analysis of cohort studies of plasma serotonin showed no relationship with depression, and evidence that lowered serotonin concentration was associated with antidepressant use ( n  = 1869). Two meta-analyses of overlapping studies examining the 5-HT 1A receptor (largest n  = 561), and three meta-analyses of overlapping studies examining SERT binding (largest n  = 1845) showed weak and inconsistent evidence of reduced binding in some areas, which would be consistent with increased synaptic availability of serotonin in people with depression, if this was the original, causal abnormaly. However, effects of prior antidepressant use were not reliably excluded. One meta-analysis of tryptophan depletion studies found no effect in most healthy volunteers ( n  = 566), but weak evidence of an effect in those with a family history of depression ( n  = 75). Another systematic review ( n  = 342) and a sample of ten subsequent studies ( n  = 407) found no effect in volunteers. No systematic review of tryptophan depletion studies has been performed since 2007. The two largest and highest quality studies of the SERT gene, one genetic association study ( n  = 115,257) and one collaborative meta-analysis ( n  = 43,165), revealed no evidence of an association with depression, or of an interaction between genotype, stress and depression. The main areas of serotonin research provide no consistent evidence of there being an association between serotonin and depression, and no support for the hypothesis that depression is caused by lowered serotonin activity or concentrations. Some evidence was consistent with the possibility that long-term antidepressant use reduces serotonin concentration.

The main aim of the present study was to estimate the prevalence of people in severe social isolation as a proxy for high risk of hikikomori using data from 29 European countries. The relationship between the presence/absence of severe social isolation and demographic and psychosocial variables was also investigated. Publicly available data from the European Social Survey (ESS) round 9 collected between August 2018 and January 2020 were used. Data from the ESS round 1 (September 2002 –December 2003) and round 10 (September 2020 –May 2022) were also examined to investigate changes in the prevalence of severe social isolation over time. Analyses were restricted to the working-age population (15–64 years). A complex sampling design to obtain weighted prevalence and results was used. The study protocol was preregistered online on the Open Science Framework ( https://osf.io/6a7br/ ). The weighted prevalence of severe social isolation was 2.01% for the sample from the ESS 1, 1.77% for the sample from the ESS 9, and 1.71% for the sample from the ESS 10, indicating a decrease over time, mainly in males. Logistic regression models showed that different sociodemographic factors (e.g., being retired, being permanently sick or disabled, doing housework, living in Central and Eastern Europe, living uncomfortably on household income, having no income) were associated with severe social isolation. Further, feeling unsafe when walking alone in the neighbourhood after dark, low social trust, and support, decreased happiness and lack of future planning correlated with severe social isolation after adjustment for the effect of sociodemographic factors was made. In this study, the prevalence of severe social isolation as a proxy for hikikomori in European countries is in line with that found by previous representative studies conducted in Asian countries. The novelty of the findings as well as implications for hikikomori research are discussed according to recent scientific literature.

BackgroundThere is ongoing controversy whether antidepressant use alters suicide risk in adults with depression and other treatment indications.MethodsSystematic review of observational studies, searching MEDLINE, PsycINFO, Web of Science, PsycARTICLES and SCOPUS for case–control and cohort studies. We included studies on depression and various indications unspecified (including off-label use) reporting risk of suicide and/or suicide attempt for adult patients using selective serotonin reuptake inhibitors (SSRI) and other new-generation antidepressants relative to non-users. Effects were meta-analytically aggregated with random-effects models, reporting relative risk (RR) estimates with 95% CIs. Publication bias was assessed via funnel-plot asymmetry and trim-and-fill method. Financial conflict of interest (fCOI) was defined present when lead authors’ professorship was industry-sponsored, they received industry-payments, or when the study was industry-sponsored.ResultsWe included 27 studies, 19 on depression and 8 on various indications unspecified (n=1.45 million subjects). SSRI were not definitely related to suicide risk (suicide and suicide attempt combined) in depression (RR=1.03, 0.70–1.51) and all indications (RR=1.19, 0.88–1.60). Any new-generation antidepressant was associated with higher suicide risk in depression (RR=1.29, 1.06–1.57) and all indications (RR=1.45, 1.23–1.70). Studies with fCOI reported significantly lower risk estimates than studies without fCOI. Funnel-plots were asymmetrical and imputation of missing studies with trim-and-fill method produced considerably higher risk estimates.ConclusionsExposure to new-generation antidepressants is associated with higher suicide risk in adult routine-care patients with depression and other treatment indications. Publication bias and fCOI likely contribute to systematic underestimation of risk in the published literature.RegistrationOpen Science Framework, https://osf.io/eaqwn/

A serious form of social withdrawal, initially described within Japan as hikikomori, has received increasing attention from the international scientific community during the last decade. The 25-item Hikikomori Questionnaire (HQ-25) was initially developed and validated in Japan. To date, data on its psychometric properties in other populations where cases of hikikomori have been described are still scarce. Thus, the aims of this study were to (1) translate, adapt, and validate the Italian version of the HQ-25 analyzing its psychometric properties; and (2) verify the association between hikikomori and personality functioning, social support, and problematic Internet use. A sample of 372 Italian adults aged 18 to 50 years completed the HQ-25 and measures of psychoticism, personality dysfunction, social support, and problematic Internet use were employed to test the convergent validity of the HQ-25. The data showed a satisfactory fit for a three-factor model, significantly better than a one-factor model. The three factors (socialization, isolation, and emotional support, as in the original study on the HQ-25) correlated positively with psychoticism, personality dysfunction, and problematic Internet use, and correlated negatively with social support. A lifetime history of hikikomori was present in 1.1% of the sample (n = 4). This is the first study to use the Italian validated version of the HQ-25 with an adult population. The findings from this study provide evidence of the satisfactory psychometric properties of the Italian version of the HQ-25 and support further investigation of the HQ-25 as an instrument to help screen for and investigate the presence of hikikomori.

To investigate if observational studies showing favorable results for antidepressants on suicidal behavior (reduced risk) are preferably and more easily published in psychiatric journals and cited more often compared to studies with unfavorable results (increased risk). Prespecified secondary analysis, including 27 original studies selected through a systematic review of observational studies reporting associations between the use of newer antidepressant drugs and suicide risk. Independent of study quality, studies reporting favorable results were more frequently published in psychiatric than nonpsychiatric journals and were more often conducted by lead authors with financial conflicts of interest (fCOI). Within psychiatric journals, lead authors with fCOI published in journals with a higher impact factor (IF) and ranking. Within psychiatric journals, favorability of results also correlated with citation frequency, IF, and journal ranking, but these associations became weaker and inconclusive after adjusting for study quality. Results for ease of publishing were inconclusive. Studies reporting unfavorable results (increased suicide risk with antidepressant exposure) are less likely to be published in psychiatric journals. Lead authors with fCOI report more favorable results, and their studies are published in the most prestigious psychiatric journals. This may create a biased evidence base and an unbalanced dissemination and appraisal of findings within psychiatry.

PurposeThe burden of mental health and substance use disorders among Italian young people have not yet been presented in detail, despite adolescents and young adults aged between 10 and 24 years constitute 14.5% of the Italian population. Therefore, the aim of this study was to provide data on the health burden of mental health and substance use disorders among young people (10–24 years) in Italy between 1990 and 2019.MethodsEcological study design using data from the Global Burden of Disease Study 2019. Age- and sex-specific prevalence and years lived with disability (YLDs) of mental health and substance use disorders with the uncertainty intervals were reported as well as their percentual changes between 1990 and 2019.ResultsPrevalence and YLDs rates of mental health and substance use disorders showed negative trends overall between 1990 and 2019. However, diagnoses of attention-deficit/hyperactivity, autism spectrum, conduct and eating (among males) disorders increased as well as cocaine use disorder. The highest levels of disability in terms of YLDs were due to anxiety, depressive, conduct and eating disorders and alcohol use, amphetamine use and opioid use disorders. The disease burden was higher in middle-late adolescence and young adulthood than early adolescence, among females than males for mental health disorders and among males compared to females for substance use disorders.ConclusionFindings of the study highlighted disorder-specific patterns of prevalence and YLDs rates and were discussed considering previous research. The public health system should continuously sustain mental health promotion and prevention efforts in young people.

Background: COVID-19 containment measures and the uncertainties associated with the pandemic may have contributed to changes in mental health risks and mental health problems in university students. Due to the high burden of the disease, depression is of particular concern. However, knowledge about the prevalence of depressive symptoms in Swiss university students during the pandemic is limited. We therefore assessed the prevalence of depressive symptoms and their change during the COVID-19 pandemic in a large sample of Swiss university students. Methods: We assessed depressive symptoms in two cross-sectional cohorts of university students (n = 3571) in spring and autumn 2020 during the COVID-19 pandemic and compared them with a matched sample of the Swiss national population (n = 2328). Binary logistic regression models estimated prevalence with corresponding 95% confidence intervals (95% CI). Results: Adjusted prevalence of depressive symptoms in female (30.8% (95% CI: 28.6–33.0)) and male students (24.8% (95% CI: 21.7–28.1)) was substantially higher than in the matching female (10.9% (95% CI: 8.9–13.2)) and male (8.5% (6.6–11.0)) pre-pandemic national population. Depressive symptoms in the two consecutive student cohorts did not significantly differ. Conclusions: More than a quarter of Swiss university students reported depressive symptoms during the COVID-19 pandemic, which was substantially higher as compared to the matched general population. Universities should introduce measures to support students in such times of crisis and gain an understanding of the factors impacting mental health positively or negatively and related to university structures and procedures.

In recent years, researchers have begun to explore the implications of shyness for the psychosocial wellbeing of children and adolescents, exploring its association with internalizing problems. Research in an Italian context is hindered by the lack of a validated self-report measure of shyness. We report two studies aimed to assess the psychometric properties of an Italian translation of the Children's Shyness Questionnaire (CSQ-it) and investigate its correlations with convergent and divergent constructs. The first study aimed to examine associations between CSQ-it and self-report measures of anxiety and somatic symptoms and attachment with parents and peers. The second study aimed to investigate its relations to internet addiction. The self-report measures were completed by 550 participants in the first study and 131 participants in the second study. Parents provided information on their child's problems. Psychometric properties were assessed by Cronbach's alpha in both studies and by exploratory and confirmatory factor analysis in Study 1. The relations between shyness and measures of internalizing problems and attachments were analyzed by correlational methods. In Study 2 a moderated mediation model tested the hypothesis that the relationship between shyness and internet addiction is mediated by somatic symptoms and that shyness moderates the relationship between somatic symptoms and internet addiction. The reliability and validity of the Italian Version of the Children's Shyness Questionnaire were satisfactory. Results from confirmatory factor analyses confirmed the single-factor model of the questionnaire previously identified in North American and Chinese studies. There were significant correlations between shyness, anxious and somatic symptomatology, impaired psychosocial functioning and specific components of attachment relationships. In Study 2 the indirect effect of shyness on internet addiction through somatic symptoms was significant as well as significantly moderated for high shyness scores but not for low levels of shyness. To our knowledge this is the first study that explored the psychometric proprieties of the Children's Shyness Questionnaire in the Italian context. Findings demonstrated that this self-reported measure of shyness has sound psychometric properties and can be used as a sensitive and appropriate instrument for the assessment of shyness in children and adolescents.

Background The present study analysed data on children and adolescents with a diagnosis of attention-deficit/hyperactivity disorder (ADHD) who were referred to the ADHD reference centre of Scientific Institute IRCCS E. Medea (Brindisi, Italy) for ADHD pharmacotherapy initiation and monitoring overtime. The main aim of the study was to examine differences in pharmacological treatment status (i.e., treatment continuation vs discontinuation) between patients. Methods Seventy-seven children and adolescents (mean age at pharmacotherapy initiation = 9.5, standard deviation = 2.6) with ADHD received drugs treatment for ADHD at the reference center between January, 2013 and May, 2022. Demographic and clinical data were obtained from the Italian Registry for ADHD and medical records. Child Behavior Checklist (CBCL) available data were used. Results Pharmacological treatment status was examined for patients ( n  = 63) with at least 12 months of follow-up after the first pharmacological treatment for ADHD. After starting pharmacotherapy treatment, 77.8% ( n  = 49) patients were still on treatment whereas 22.2% ( n  = 14) discontinued it. No between group difference were observed in demographic and clinical data except for the intelligence quotient/intellectual disability and rule-breaking behavior ( n  = 40). Conclusions This study stressed the need of periodical assessments, monitoring difficulties with treatment and/or reasons for poor treatment compliance to provide individualized care.