Type of cycle, temperament and childhood trauma are associated with lithium response in patients with bipolar disorders.

BACKGROUND: Lithium stands as the gold standard in treating bipolar disorders (BD). Despite numerous clinical factors being associated with a favorable response to lithium, comprehensive studies examining the collective influence of clinical variables alongside psychopathological dimensions are lacking. Our study aims to enhance comprehension of lithium response in individuals with BD by integrating clinical variables with psychopathological traits and early adverse events. METHODS: We assessed 201 patients with BD for clinical characteristics, childhood trauma, temperament traits, impulsivity, and aggression. Lithium response was evaluated using the gold standard Alda scale, and predictors of lithium response were estimated through a multivariate model. RESULTS: On the total sample, 61 (30.3%) patients were lithium responders according to the Alda scale. Comparatively, lithium responders, in contrast to non-responders, demonstrated a higher prevalence of the mania-depression-interval (MDI) cycle, a more frequent diagnosis of BD type I, and reported an earlier age of onset. They also exhibited less lifetime substance abuse, emotional, physical, and sexual abuse, while scoring higher on hyperthymic and irritable temperament scales. In multivariate analyses, only the MDI cycle (OR,3.47; 95%CI,1.61-7.50) hyperthymic (OR,1.20; 95%CI,1.02-1.41) and irritable temperament (OR,1.28; 95%CI,1.08-1.52) persisted as significant predictors of a positive response to lithium treatment, while emotional (OR,0.87; 95%CI,0.76-0.98) and physical abuse (OR,0.83; 95%CI,0.70-0.98) were predictors of non-response. CONCLUSIONS: In evaluating lithium response in BD, our study highlights the importance of considering clinical variables alongside temperament and childhood adversities. The assessment of hyperthymic and irritable temperament, emotional and physical abuse together with the type of cycle is of particular importance. Furthermore, our findings underscore the significance of systematically assessing the type of cycle in patients with BD through the use of life charts.

Understanding University Students' Perspectives towards Digital Tools for Mental Health Support: A Cross-country Study.

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.

Substance use disorders in adults with attention-deficit/hyperactivity disorder: The role of affective temperament.

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.

Tolerability of vortioxetine compared to selective serotonin reuptake inhibitors in older adults with major depressive disorder (VESPA): a randomised, assessor-blinded and statistician-blinded, multicentre, superiority trial.

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 depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the "2016 Call for Independent Drug Research".

Longitudinal outcomes of a work inclusion program in mental health departments in the city of Milan.

BACKGROUND: Work functioning impairment is a key diagnostic and prognostic criterion in patients with psychiatric disorders and work inclusion is a major goal of their therapeutic pathway. Since 2009, the Regional Innovative Program (PIR) TR106, promoted by ASST Fatebenefratelli-Sacco of Milan in collaboration with other Departments of Mental Health and Addictions (DSMDs) in the town of Milan (Italy), has been developing the employment inclusion of psychiatric patients. AIMS: The objective of this study is to evaluate its outcomes over 8 years of observation. METHOD: We reported the results of a retrospective epidemiologic analysis on 2,142 interventions on 1,066 patients recruited, investigating PIR TR106 outcomes per year focusing on different subgroups. We focused on 'positive', 'negative', and 'other' outcomes. RESULTS: We preliminary calculated job maintenance interventions (5%, 107) and excluded these interventions from the overall. We observed 29 job firing (1.4%) and 15 job resignations (0.7%) as negative results (equal to 2.2% of the total) and 388 job hiring (16.6%), 647 traineeships (31.8%), and 413 work formation (20.3%) as positive outcomes (equal to 68.75%). In other outcomes (29.1%) we found 305 dismissals from PIR TR 106 (15%) and transitory outcomes (14.1%).Job hiring increased from 8.9% in 2012 to 23.8 % in 2019 (p < .001), while the dismissals diminished from 26.7% to 13.3% (p < .001). The effectiveness of traineeships in terms of job hiring increased in the ratio of annual job hiring versus job traineeship (+48.8%). The majority of hired patients (15.1%) were affected by a psychotic disorder. A significant hiring increase was observed in patients with psychotic disorders and personality disorders (p < .005). CONCLUSIONS: PIR-TR106 represents a territorial employment inclusion program with progressively increasing effectiveness and specificity, as suggested by changes in outcomes during the 8-year observation. The adaptive capacity and sustainability of the intervention are worth further investigation.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

The Kynurenine Pathway in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis of Blood Concentrations of Tryptophan and Its Catabolites.

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.

Exploring depression in people with schizophrenia spectrum disorders: A cross-sectional analysis of the clinical relationship with Positive and Negative Syndrome Scale dimensions.

OBJECTIVE: Evidence on the relationship of depression with clinical dimensions of schizophrenia remains limited. This cross-sectional study aimed at exploring the association of depression with the Positive and Negative Syndrome Scale (PANSS) dimensions in people with schizophrenia spectrum disorders (SSD). METHODS: Trained assessors administered PANSS to measure core symptoms of schizophrenia and the Calgary Depression Scale for Schizophrenia (CDSS) to measure depressive features. Multiple logistic regression analyses were carried out to analyse the association of depression with PANSS overall score and related dimensions. RESULTS: We included 231 inpatients with SSD (mean age:42.4±12.9 years; males: 58.9%; mean PANSS overall score:82.5±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 [coeff.], standard error [SE]: 0.029, 0.008; p<0.001) and General Psychopathology (coeff., SE: 0.118, 0.023; p<0.001) PANSS scores. We found an inverse relationship between depression and positive symptoms (coeff., SE: -0.088, 0.028; p=0.002). No association between depressive and negative symptoms was estimated. CONCLUSIONS: Despite some limitations, our study shows that people affected by SSD with depressive features are likely to show more overall and general psychopathology symptoms, though lower positive symptoms. Additional studies are needed to explore the generalizability of our findings.

Anxious distress in people with major depressive episodes: a cross-sectional analysis of clinical correlates.

OBJECTIVE: Most people with major depressive episodes meet the criteria for the anxious distress (AD) specifier defined by DSM-5 as the presence of symptoms such as feelings of tension, restlessness, 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 socio-demographic 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 depressive and manic (mixed) 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). 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 help clinicians to better contextualize AD in the context of major depressive episodes.

Acute stress symptoms in general population during the first wave of COVID lockdown in Italy: Results from the COMET trial.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic is an unprecedented traumatic event that has severely impacted social, economic, and health well-being worldwide. The COvid Mental hEalth Trial was specifically designed to evaluate the impact of the COVID-19 pandemic and its containment measures on the mental health of the Italian general population in terms of COVID-19-related acute stress disorder (ASD) symptoms. METHODS: The present cross-sectional study is based on an online survey carried out in the period March-May 2020. Italian general adult population was invited to compile an anonymous survey, which included the severity of acute stress symptoms scale/National Stressful Events Survey Short Scale to investigate the occurrence and severity of ASD symptoms. RESULTS: The final sample consisted of 20,720 participants. During the lockdown, subjects with pre-existing mental health problems reported a statistically significant higher risk of acute post-traumatic symptoms compared to the general population (B: 2.57; 95% CI:2.04-3.09; p < .0001) and health care professionals (B: .37; 95% CI: .02-0.72; p < .05). According to multivariate regression models, the levels of acute post-traumatic symptoms (p < .0001) were higher in younger and female respondents. Social isolation and sleep disorder/insomnia represented positive predictors of acute stress (B = 3.32, 95% CI = 3.08-3.57). CONCLUSIONS: Concerns about the risk of infection as well as social isolation caused a higher incidence of acute post-traumatic stress symptoms that may predict the subsequent development of post-traumatic stress disorder symptoms in the long term.

The impact of MDQ positivity on quality of life impairment: Does it support the hypothesis of "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS)?

Background: DSM-5 separates bipolar (BD) from depressive disorders, but some experts consider BD as part of a spectrum of mood disorders. The interpretation of numerous false positives of BD screened by the Mood Disorders Questionnaire (MDQ) is part of this debate. Recent study results suggest that the worsening of health-related quality of life (H-Qol) associated with MDQ positivity does not depend solely on mood disorders. This study aims to clarify whether the impairment may be due to other concomitant disorders, unrelated to mood disorders, leading to a worsening of H-Qol. Additionally, the study aims to explore if MDQ positivity itself observe clinical significance. Design and methods: The study involved pairs of cases (MDQ+) and controls (MDQ-) matched for sex, age, and absence of DSM-IV psychiatric comorbidity. The impact of MDQ positivity on the quality of life in a sample of MDQ+ comorbid with MDD was measured and compared to impact of MDD in other chronic disorders. Results: The H-Qol was significantly worse in MDQ+ than in controls (both groups without any psychiatric co-morbidity). The worsening was similar to severe chronic disorders The burden of worsening quality of life due to MDD was mild in another sample of MDQ positives with comorbid MDD. Conclusion: The study hypothesizes that MDQ positivity may be related to hyperactivation and dysregulation of rhythms typical of stress disorders. In fact, MDQ+ was found strongly related to sleep disturbances. Future studies could verify if a "Dysregulation of Mood, Energy, and Social Rhythms Syndrome" (DYMERS), causes worsening the H-Qol in MDQ+.

Blood concentrations of anterior pituitary hormones in drug-naïve people with first-episode psychosis: A systematic review and meta-analysis.

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.

Influence of intrinsic and extrinsic religiosity on youth cannabis use: A structural equation modelling analysis on national survey on drug use and health (NSDUH) 2015-2019.

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 effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial.

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 ± 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 ± 0.1 h vs. 4.9 ± 0.02; p < 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p < 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p < 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p < 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media.

Characterizing the clinical profile of mania without major depressive episodes: a systematic review and meta-analysis of factors associated with unipolar mania.

BACKGROUND: The diagnostic concept of unipolar mania (UM), i.e. the lifetime occurrence of mania without major depressive episodes, remains a topic of debate despite the evidence accumulated in the last few years. We carried out a systematic review and meta-analysis of observational studies testing factors associated with UM as compared to bipolar disorder with a manic-depressive course (md-BD). METHODS: Studies indexed up to July 2022 in main electronic databases were searched. Random-effects meta-analyses of the association between UM and relevant correlates yielded odds ratio (OR) or standardized mean difference (SMD), with 95% confidence intervals (CIs). RESULTS: Based on data from 21 studies, factors positively or negatively associated with UM, as compared to md-BD, were: male gender (OR 1.47; 95% CI 1.11-1.94); age at onset (SMD -0.25; 95% CI -0.46 to -0.04); number of hospitalizations (SMD 0.53; 95% CI 0.21-0.84); family history of depression (OR 0.55; 95% CI 0.36-0.85); suicide attempts (OR 0.25; 95% CI 0.19-0.34); comorbid anxiety disorders (OR 0.35; 95% CI 0.26-0.49); psychotic features (OR 2.16; 95% CI 1.55-3.00); hyperthymic temperament (OR 1.99; 95% CI 1.17-3.40). The quality of evidence for the association with previous suicide attempts was high, moderate for anxiety disorders and psychotic features, and low or very low for other correlates. CONCLUSIONS: Despite the heterogeneous quality of evidence, this work supports the hypothesis that UM might represent a distinctive diagnostic construct, with peculiar clinical correlates. Additional research is needed to better differentiate UM in the context of affective disorders, favouring personalized care approaches.

The role of BDNF in major depressive disorder, related clinical features, and antidepressant treatment: Insight from meta-analyses.

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.

Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a one-year mirror-image analysis from the STAR Network Depot study.

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.

Long-acting injectable antipsychotics for the treatment of bipolar disorder: evidence from mirror-image studies.

Clinical trials and real-world data have shown that long-acting injectable antipsychotics (LAIs) might be an effective therapeutic option also for people with bipolar disorder (BD). However, complementing evidence from mirror-image studies investigating LAIs in BD is scattered and has not been systematically evaluated so far. We thus performed a review of observational mirror-image studies testing the effectiveness of LAI treatment on clinical outcomes in people with BD. Embase, MEDLINE, and PsycInfo electronic databases were systematically searched (via Ovid) up to November 2022. We included six mirror-image studies that compared relevant clinical outcomes between the 12-months after (post-treatment period) and the 12-months before (pre-treatment period) the initiation of a LAI treatment in adults with BD. We found that LAI treatment is associated with a significant reduction in days spent in hospital and number of hospitalizations. Moreover, LAI treatment seems to be associated with a significant decrease in the proportion of individuals with at least one hospital admission, even though data on this outcome were reported by just two studies. In addition, studies consistently estimated a significant reduction of hypo-/manic relapses after LAI treatment initiation, while the effect of LAIs for depressive episodes is less clear. Finally, LAI treatment initiation was associated with a lower number of emergency department visits in the year after LAI initiation. The findings of this review seem to suggest that the use of LAIs is an effective strategy to improve major clinical outcomes in people with BD. Nonetheless, additional research, based on standardized assessments of prevalent polarity and relapses, is needed to identify the clinical characteristics of individuals with BD who are most likely to benefit from a LAI treatment.

Mental Health and COVID-19 in University Students: Findings from a Qualitative, Comparative Study in Italy and the UK.

INTRODUCTION: COVID-19 restrictions introduced several changes in university academic and social experience. Self-isolation and online teaching have amplified students' mental health vulnerability. Thus, we aimed to explore feelings and perspectives about the impact of the pandemic on mental health, comparing students from Italy and the UK. METHODS: Data were collected from the qualitative portion of "the CAMPUS study", longitudinally assessing 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. RESULTS: The explanatory model was developed from four themes identified across 33 interviews: anxiety exacerbated by COVID-19; putative mechanisms leading to poor mental health; the most vulnerable subgroups; and coping strategies. Generalised and social anxiety resulted from COVID-19 restrictions by being associated with loneliness, excessive time online, unhealthy management of time and space and poor communication with the university. Freshers, international students, and people on the extremes of the introversion/extroversion spectrum, were identified as vulnerable, while effective coping strategies included taking advantage of free time, connection with family and mental health support. The impact of COVID-19 was mostly related to academic issues by students from Italy, whereas to the drastic loss of social connectedness by the UK sample. CONCLUSIONS: Mental health support for students has an essential role, and measures that encourage communication and social connectedness are likely to be beneficial.

Clinical correlates of comorbid attention deficit hyperactivity disorder in adults suffering from bipolar disorder: A meta-analysis.

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). CONCLUSION: Comorbid bipolar disorder/attention deficit hyperactivity disorder may have some distinctive clinical features including an earlier onset of bipolar disorder and higher comorbid alcohol/substance use disorder rates. Further research is needed to identify additional clinical characteristics of this comorbidity.