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Major depressive disorder (MDD) represents a major health issue in adolescents and young adults, leading to high levels of disability and profoundly impacting overall functioning. The clinical presentation of MDD in this vulnerable age group may slightly differ from what can be observed in adult populations, and psychopharmacological strategies do not always lead to optimal response. Resistance to antidepressant treatment has a prevalence estimated around 40% in youths suffering from MDD and is associated with higher comorbidity rates and suicidality. Several factors, encompassing biological, environmental, and clinical features, may contribute to the emergence of treatment-resistant depression (TRD) in adolescents and young adults. Furthermore, TRD may underpin the presence of an unrecognized bipolar diathesis, increasing the overall complexity of the clinical picture and posing major differential diagnosis challenges in the clinical practice. After summarizing current evidence on epidemiological and clinical correlates of TRD in adolescents and young adults, the present review also provides an overview of possible treatment strategies, including novel fast-acting antidepressants. Despite these pharmacological agents are promising in this population, their usage is expected to rely on risk-benefit ratio and to be considered in the context of integrated models of care.

Abstract Background Bipolar disorder is one of the most burdensome severe mental disorders, characterized by high levels of personal and social disability. Patients often need an integrated pharmacological and non-pharmacological approach. Lithium is one of the most effective treatments available not only in psychiatry, but in the whole medicine, and its clinical efficacy is superior to that of other mood stabilizers. However, a declining trend on lithium prescriptions has been observed worldwide in the last 20 years, supporting the notion that lithium is a ‘forgotten drug’ and highlighting that the majority of patients with bipolar disorder are missing out the best available pharmacological option. Based on such premises, a narrative review has been carried out on the most common “misconceptions” and “stereotypes” associated with lithium treatment; we also provide a list of “good reasons” for using lithium in ordinary clinical practice to overcome those false myths. Main text A narrative search of the available literature has been performed entering the following keywords: “bipolar disorder”, “lithium”, “myth”, “mythology”, “pharmacological treatment”, and “misunderstanding”. The most common false myths have been critically revised and the following statements have been proposed: (1) Lithium should represent the first choice for the treatment of patients with bipolar disorder; (2) lithium treatment is effective in different patients’ groups suffering from bipolar disorder; (3) Drug–drug interaction risk can be easily managed during lithium treatment; (4) The optimal management of lithium treatment includes periodical laboratory tests; (5) Slow-release lithium formulation has advantages compared to immediate release formulation; (6) Lithium treatment has antisuicidal properties; (7) Lithium can be carefully managed during pregnancy. Conclusions In recent years, a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar disorder has been highlighted. It is time to disseminate clear and unbiased information on the clinical efficacy, effectiveness, tolerability and easiness to use of lithium treatment in patients with bipolar disorder. It is necessary to reinvigorate the clinical and academic discussion about the efficacy of lithium, to counteract the decreasing prescription trend of one of the most effective drugs available in the whole medicine.

Abstract Background Use of social media (SM) has exponentially grown particularly among youths in the past two years, due to COVID-19-related changing lifestyles. Based on the Italian COvid Mental hEalth Trial (COMET), we investigated the association between SM use and depressive symptoms among Italian young adults (aged 18–24). Methods The COMET is a nationwide multi-center cross-sectional study that investigated socio-demographic data, social networking addiction (BSNAS), depression, anxiety, and stress (DASS-21), as well as impulsiveness (BIS-15) and aggressiveness (AQ) in a large sample of youngsters, in order to assess the association between BSNAS and DASS-21 indices. Mediation analyses were performed to evaluate the role of impulsiveness and aggressive personality traits in the association between SM use (SMU) and depression. Results 75.8% of the sample (n = 491) had a problematic SMU. SMU was reduced by high AQ and high DASS-21 scores (F = 42.338, p

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

Introduction The COVID-19 outbreak and the related containment measures led to the emergence of psychological distress in youth populations, possibly due to concern for their families, social isolation, increased time spent on the Internet and social media, and anxiety about the future. Objectives The study aims to evaluate differences in the access of children, adolescents, and young adults to a psychiatric emergency setting before and after the onset of the COVID-19 pandemic. Methods Data concerning the psychiatric consultations carried out at the Emergency Department of the University Hospital of Perugia was collected. Socio-demographic and clinical information, including diagnostic and treatment features, was entered into an electronic database. We considered two different time spans, one before (01.06.2017-31.12.2018) and one after (01.06.2020-31.12.2021) the COVID-19 pandemic outbreak. The characteristics of consultations carried out before and after the pandemic outbreak were compared by means of bivariate analyses (p

Introduction The use of diagnostic categories, although useful, fails in capturing the psychopathological complexity of the individual case. As for schizophrenia spectrum disorders, positive symptoms are not always included in the presentation, so further dimensions should be considered for a correct diagnosis. Objectives To describe the importance of dimensional diagnosis in schizophrenia spectrum disorder based on a clinical experience Methods We report the case of a late-onset schizophrenia spectrum disorder with an affective presentation Results I. is a 44-year-old woman who accessed the Community Mental Health Center due to subjective memory complains. After clinical evaluation, depressive symptoms and circadian rhythm disturbances emerged. The patient also reported dissociative experiences, which emerged after her brother’s death. She underwent a neurological visit that excluded the possible early manifestation of a neurodegenerative disorder. Quetiapine was at first prescribed, due to the possible action on both insomnia and mood symptoms, with insufficient response. After a few visits, a deeper mental state examination revealed the presence of delusions. The patient also reported having experienced hallucinations. Psychotic symptoms appeared to be persistent and pervasive. We changed the antipsychotic to full-dose olanzapine, with good response. After a six-month observation, the patient was diagnosed with schizophrenia. Conclusions The diagnosis of late-onset schizophrenia should take into account clinical history, drugs response, and the evaluation of different psychopathological dimensions Disclosure of Interest None Declared

Introduction Suicide is the fourth leading cause of death among adolescents and young adults (AYA) (Czyz EK, King CA. J Clin Child Adolesc Psychol.2015;44(1):181-19), and psychiatric disorders are a major contributing factor (WHO Global Health Estimates 2000-2019). Studies focusing on suicidality in Italian inpatients samples are scant. Objectives The present cross-sectional study aimed to define clinical variables associated with suicidality related phenomena in a sample of young inpatients. The main objectives were to assess the prevalence of suicidal ideation and deliberate self-harm in inpatients aged 16–24 years and to determine the relationship between suicidal behaviours and psychiatric disorders. Methods This retrospective study was conducted in a naturalistic setting, at the Psychiatric Inpatient Unit, Perugia Hospital/Local Mental Health Unit 1, from January 2018 to December 2019. Sociodemographic information, clinical history, diagnostic and treatment features were collected. Descriptive and bivariate analyses were performed (p

Introduction ADHD is a neurodevelopmental disorder that occurs in childhood and can persist in adulthood in a percentage of cases ranging from 15% to 70% (Cheung, C. H. et al. J. Psychiatr. Res. 2005; 62, 92–100). In these cases, if not treated, ADHD symptoms can cause severe dysfunction (Biederman, J., et al. Am. J. Psychiatry 2000; 157(5), 816–818) often leading to misdiagnosis. Objectives The aim of this case report is to describe the clinical picture of a 26-year-old boy with ADHD and the consequences deriving from the missed diagnosis of the disorder during childhood. Methods We report a case of undiagnosed and untreated ADHD and the ensuing consequences. Results G.V. is a boy who came to our attention complaining about a vague depressive symptomatology. After psychopathological examination we detected mood instability, with the alternance of phases characterized by deep despair and melancholy and phases of agitation with internal tension and generalized anxiety. He reported a tendency to act on an impulsive basis and an occasional abuse of cocaine together with a daily abuse of high doses of Alprazolam. During the past years the boy had been visited by several psychiatrists who made various diagnoses (borderline or avoidant personality disorder, cyclothymic disorder) and prescribed various drugs but none of these were able to stabilize the psychopathological condition. The clinical history revealed the presence of a pervasive picture of inattention and hyperactivity since childhood which had heavily conditioned the patient’s functioning over time. The inattentive pattern has persisted unchanged over the years, while the hyperactive one has improved leaving room for a stable sense of internal tension and generalized anxiety on which mood fluctuations are cyclically inscribed. A diagnosis of ADHD, combined presentation type, was made by using the DIVA-5. The patient was first prescribed lithium, which was subsequently replaced with valproic acid. After mood stabilization and the reduction of anxious symptoms prolonged-release methylphenidate was added to therapy, obtaining resolution of the clinical picture. Conclusions Almost all adults with ADHD exhibit a lifelong pattern of frequent mood swings and irritability. Given that many mental health practitioners are unfamiliar with emotional lability in adult ADHD, a bipolar, or cluster B/C personality disorder is more likely to be considered as the cause of the mood swings (Fayyad, J. et al. BJPsych 2007; 190, 402–409). An accurate collection of clinical history can guide the diagnosis and help to address adequate treatment. Disclosure of Interest None Declared

Introduction Circadian rhythms, defined as endogenous oscillations that regulate metabolism, physiology and behaviour, may be frequently disrupted in mood disorders, influencing their clinical presentation and course (Srinivasan V. et al. World J Biol Psychiatry. 2006;7(3):138-151). Objectives To characterise circadian rhythm disruptions in a population of patients with mood disorders, analysing clinical and course differences in subjects with and without clinically significant circadian rhythm alterations Methods Patients selected for this cross-sectional study were assessed with CGI-BP, HAM-D, MRS, and PANSS. Circadian rhythm disturbances were evaluated with BRIAN. Patients with clinically relevant circadian rhythm disturbances were defined as BRIAN > 36 (Mondin TC et al. J Psychiatr Res. 2017;84:98-104). Bivariate analyses were subsequently performed to compare subgroups of patients. Results In our study, 61 subjects with DD or DB were enrolled. The overall mean BRIAN test score was 40.08 ± 10.26. When comparing the BRIAN test scores, both total and subscales, between subjects with DB and DD, social rhythms were significantly more altered in subjects with DB (8.63 ± 2.90 VS 6.80 ± 2.11, p=0.034). Subjects with disruption of circadian rhythms displayed greater severity of depressive symptoms (mean total HAM-D test score 16.06±8.61 VS 8.94±5.85; p

Background: The COVID-19 pandemic has heavily impacted social, economic and health systems worldwide. Necessary confinement measures have, in turn, contributed to the occurrence of several stress-related conditions and deterioration of pre-existing mental conditions, including insomnia. Objective: The present study sought to investigate the occurrence and severity of insomnia during the COVID-19 lockdown among psychiatric patients and in the general population in the largest Italian sample examined to date. Potential factors associated with a risk of developing insomnia in the global sample were examined as well. Methods: A sample of 20,720 people (5.5% of them being psychiatric patients) was assessed through an online survey conducted during lockdown between March and May 2020. To investigate the occurrence and severity of sleep related issues, the Insomnia Severity Index (ISI) was used. In order to evaluate factors associated with the severity of insomnia in the global sample, multivariate linear regression models were performed. Results: During the lockdown, patients with pre-existing mental disorders reported a mean higher score on the ISI scale (p

IntroductionDissociative symptoms have been recently related to bipolar disorder (BD) symptomatology. Moreover, the disease burden carries on a share of perceived self-stigma that amplifies the BD impairment. Internalized stigma and dissociative symptoms often seem overlapping, leading toward common outcomes, with reduced treatment seeking and poor adherence. We hypothesize a potential relationship between dissociation and self-stigma in patients suffering from BD.Materials and methodsIn this cross-sectional study we enrolled a total of 120 adult clinically stable BD outpatients. All participants completed the Internalized Stigma of Mental Illness (ISMI), Dissociative Experiences Scale-II (DES-II), and Manchester Short Assessment of Quality of Life (MANSA).ResultsAverage age and age at BD (BD-I n = 66, 55%; BD-II n = 54, 45%) onset were 46.14 (±4.23), and 27.45 (±10.35) years, with mean disease duration of 18.56 (±13.08) years. Most participants were female (n = 71; 59.2%) and 40 (33%) of them experienced lifetime abuse, with an average of 1.05 (±0.78) suicide attempts. DES scores (mean 31.8, ±21.6) correlated with ISMI total-score, with significant association with spikes in Alienation (13.1, SD±3.1) (p < 0.001) and Stereotype (13.8, SD±3.9) (p < 0.001). Linear regression analysis has shown a significant association between DES total score and alienation (p < 0.001), stereotype (p < 0.001) and MANSA total-score (p < 0.001).DiscussionFor the first time, our data suggests that self-stigma is associated to dissociative symptoms, reducing overall quality of life in BD. The early identification of at-risk patients with previous lifetime abuse and high perceived stigma could lead the way for an ever more precise tailoring of treatment management.

IntroductionSex differences were demonstrated in bipolar disorders (BD) concerning epidemiological, clinical, and psychopathological characteristics, but consensus is lacking. Moreover, data concerning the influence of sex on treatment response in BD is contrasting. The present cross-sectional study aimed to analyze sex differences in a population of BD subjects, with specific focus on psychopathological features and treatment response.Materials and MethodsSubjects diagnosed with BD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) were recruited. Socio-demographic and clinical characteristics were collected. The Hamilton Rating Scale for Depression, the Mania Rating Scale (MRS), the brief version of the Temperament Evaluation of Memphis, Pisa and San Diego—Münster version (briefTEMPS-M), and the Barratt Impulsiveness Scale−11 items (BIS-11) were used for psychopathological assessment. Treatment response was appraised with the Alda Scale. We performed bivariate analyses to compare socio-demographic, clinical, and psychopathological characteristics between men and women (p < 0.05). A logistic regression was run to analyze features that were significantly associated with female sex.ResultsAmong the recruited 219 BD subjects, 119 (54.3%) were females. Women had a lower scholarity (p = 0.015) and were less frequently employed (p = 0.001). As for psychopathological features, a higher MRS total score (p < 0.001) was detected among women, as well as higher BIS-11 total score (p = 0.040), and briefTEMPS-M score for anxious temperament (p = 0.006). Men showed higher prevalence of DSM-5 mixed features (p = 0.025), particularly during a depressive episode (p = 0.014). Women reported longer duration of untreated illness (DUI) (p < 0.001). There were no sex differences in the Alda Scale total score when considering the whole sample, but this was significantly higher among men (p = 0.030) when evaluating subjects treated with anticonvulsants. At the logistic regression, female sex was positively associated with longer DUI (p < 0.001; OR 1.106, 95% CI 1.050–1.165) and higher MRS total score (p < 0.001; OR 1.085, 95% CI 1.044–1.128) and negatively associated with employment (p = 0.003; OR 0.359, 95% CI 0.185–0.698) and DSM-5 mixed features (p = 0.006; OR 0.391, 95% CI 0.200–0.762).ConclusionsThe clinical presentation of BD may differ depending on sex. The severity of BD should not be neglected among women, who may also display worse treatment response to anticonvulsants.

IntroductionAdolescents and young adults represent a vulnerable population in the context of the Coronavirus disease 2019 (COVID-19) pandemic. The present retrospective study aims to investigate the pandemic’s psychological impact on adolescents and young adults by analyzing data from an outpatient mental health service dedicated to youths in Umbria, central Italy.Materials and MethodsThe clinical charts of subjects aged 14–24 who first accessed the service in the timeframe between March 1st, 2019, and February 28th, 2021, were reviewed. Subjects were divided into two subgroups according to the period of time when they accessed the service (pre-COVID-19 vs. during- COVID-19 outbreak). Bivariate analyses were performed using the Chi-square test and the Welch’s t-test. A secondary analysis was performed considering only subjects suffering from psychiatric disorders. Furthermore, data concerning individuals who were already followed by the service before the pandemic were analyzed by the McNemar’s test and the t-paired test to assess changes in treatment features.ResultsThe number of new accesses during the pandemic period remained stable. After the emergency onset, youths accessing the service showed a higher prevalence of anxiety disorders (p = 0.022). During the COVID-19 period, services were more frequently delivered by using a digital mental health approach (p = 0.001). Psychopharmacological treatment was more frequently prescribed among subjects that were referred to the service after the pandemic onset (p = 0.033). As for substance use, a highly significant reduction in opioid use was observed (p = 0.003). Family therapy was delivered less frequently in the during-COVID-19 subgroup, especially in the subpopulation of subjects suffering from psychiatric disorders (p = 0.013). When considering subjects referred to the service in the pre-COVID-19 period, the number of interventions provided to this population increased after the pandemic outbreak (p = 0.038).ConclusionIn the context of the COVID-19-related public health crisis, youths represent an at-risk population for which pathways to care should be reinforced, and targeted interventions, including psychosocial treatments, should be implemented.

IntroductionBipolar disorder (BD) onset typically occurs between 15 and 30 years, being diagnosed under the age of 50 in 90% of cases, named “non-late onset BD” (non-LOBD). However, clinical observation of late-onset BD (LOBD) raised some concern regarding a differential psychopathological pattern, outcomes and treatment, including a specific affective temperament vulnerability. Therefore, an exploratory study in the “real world” was carried out by investigating psychopathological and temperamental features of a psychogeriatric cohort of LOBD and non-LOBD subjects.MethodsA total of 180 patients affected with BD-I, BD-II, and Cyclothymic Disorder were screened in a Mood Disorder Outpatient Service, during the timeframe January 2019-August 2021. Out of 78 enrolled outpatients, 66 (33 non-LOBD, 33 LOBD) were recruited, by the retrospective collection of sociodemographic, cognitive, psychopathological and clinical assessment, including the short-version of the Temperament Evaluation of Memphis, Pisa, and San Diego (TEMPS-M).ResultsLOBD is significantly associated with higher rates of BD-II diagnosis (χ2 = 27.692, p < 0.001), depressive episodes (p = 0.025), mixed states (p = 0.009), predominant depressive and anxious affective temperaments (p < 0.001). Non-LOBD is significantly associated with higher endocrinological (χ2 = 6.988, p = 0.008) and metabolic comorbidity (χ2 = 5.987, p = 0.014), a diagnosis of BD-I, manic episodes, and predominant hyperthymic affective temperaments (p = 0.001). GDS (p < 0.001) and MSRS (p = 0.005) scores were significantly higher in LOBD.ConclusionFurther longitudinal studies with larger sample sizes and a control group are needed to determine whether LOBD may represent a distinct psychopathological entity from non-LOBD and evaluate differences (if any) in terms of prognosis and treatment between non-LOBD and LOBD.

Abstract Background Symptoms of depression are transdiagnostic heterogenous features frequently assessed in psychiatric disorders, that impact the response to first-line treatment and are associated with higher suicide risk. This study assessed whether severe mental pain could characterize a specific phenotype of severely depressed high-risk psychiatric patients. We also aimed to analyze differences in treatments administered. Methods 2,297 adult patients (1,404 females and 893 males; mean age = 43.25 years, SD = 15.15) treated in several Italian psychiatric departments. Patients were assessed for psychiatric diagnoses, mental pain, symptoms of depression, hopelessness, and suicide risk. Results More than 23% of the patients reported high depression symptomatology and high mental pain (HI DEP/HI PAIN). Compared to patients with lower symptoms of depression, HI DEP/HI PAIN is more frequent among females admitted to an inpatient department and is associated with higher hopelessness and suicide risk. In addition, HI DEP/HI PAIN (compared to both patients with lower symptoms of depression and patients with higher symptoms of depression but lower mental pain) were more frequently diagnosed in patients with personality disorders and had different treatments. Conclusions Patients reporting severe symptoms of depression and high mental pain presented a mixture of particular dangerousness (high trait hopelessness and the presence of suicide ideation with more frequency and less controllability and previous suicide behaviors). The presence of severe mental pain may act synergically in expressing a clinical phenotype that is likewise treated with a more complex therapeutic regime than that administered to those experiencing symptoms of depression without mental pain.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

Introduction Smart healthcare monitoring allows detecting health conditions using Big Data, namely aggregated data concerning physiological and behavioral parameters. The continuous collection of data from smart-devices performed by the Ecological Momentary Assessment approach represents a promising application of Big Data. Objectives This preliminary study was aimed at developing a research protocol focused on the use of Big Data in evaluating the impact of urban environment, affected by a variety of potentially damaging anthropogenic actions, on illness relapses in Bipolar Disorders (BD). Methods This pilot study was designed by researchers from Departments of Psychiatry and Engineering (CIRIAF), University of Perugia. Environmental, physiological, and behavioral parameters and smart-devices aimed at collecting Big Data were identified. Subjects aged 18-65, affected by BD in current euthymic state referring to the University/General Hospital of Perugia will be recruited. Results Subjects will undergo a baseline visit and three monitoring visits during one year. Wearable devices will be provided for collecting data about environmental and physiological parameters. Behavioral data will be collected through smartphone accelerometers, GPS, and overall smartphone use. Big data will be stored into an online platform that will provide real-time feedback concerning the recorded variables. Clinical information concerning BD relapses will be collected. Machine learning techniques, integrated to deterministic analysis of urban environmental conditions, will be used to create possible predictive models for BD relapses. Conclusions The present project could allow the creation of a new operative platform for a better health management system correlating real-time Big Data to specific clinical features of BD. Disclosure No significant relationships.

Abstract Background When facing a traumatic event, some people may experience positive changes, defined as posttraumatic growth (PTG). Methods Understanding the possible positive consequences of the pandemic on the individual level is crucial for the development of supportive psychosocial interventions. The present paper aims to: 1) evaluate the levels of PTG in the general population; 2) to identify predictors of each dimension of post-traumatic growth. Results The majority of the sample (67%, N = 13,889) did not report any significant improvement in any domain of PTG. Participants reported the highest levels of growth in the dimension of “appreciation of life” (2.3 ± 1.4), while the lowest level was found in the “spiritual change” (1.2 ± 1.2). Female participants reported a slightly higher level of PTG in areas of personal strength (p

The COVID-19 pandemic and its related containment measures—mainly physical distancing and isolation—are having detrimental consequences on the mental health of the general population worldwide. In particular, frustration, loneliness, and worries about the future are common reactions and represent well-known risk factors for several mental disorders, including anxiety, affective, and post-traumatic stress disorders. The vast majority of available studies have been conducted in China, where the pandemic started. Italy has been severely hit by the pandemic, and the socio-cultural context is completely different from Eastern countries. Therefore, there is the need for methodologically rigorous studies aiming to evaluate the impact of COVID-19 and quarantine measures on the mental health of the Italian population. In fact, our results will help us to develop appropriate interventions for managing the psychosocial consequences of pandemic. The “COVID-IT-mental health trial” is a no-profit, not-funded, national, multicentric, cross-sectional population-based trial which has the following aims: a) to evaluate the impact of COVID-19 pandemic and its containment measures on mental health of the Italian population; b) to identify the main areas to be targeted by supportive long-term interventions for the different categories of people exposed to the pandemic. Data will be collected through a web-platform using validated assessment tools. Participants will be subdivided into four groups: a) Group 1—COVID-19 quarantine group. This group includes the general population which are quarantined but not isolated, i.e., those not directly exposed to contagion nor in contact with COVID-19+ individuals; b) Group 2—COVID-19+ group, which includes isolated people directly/indirectly exposed to the virus; c) Group 3—COVID-19 healthcare staff group, which includes first- and second-line healthcare professionals; d) Group 4—COVID-19 mental health, which includes users of mental health services and all those who had already been diagnosed with a mental disorder. Mental health services worldwide are not prepared yet to manage the short- and long-term consequences of the pandemic. It is necessary to have a clear picture of the impact that this new stressor will have on mental health and well-being in order to develop and disseminate appropriate interventions for the general population and for the other at-risk groups.

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic is an unprecedented traumatic event influencing the healthcare, economic, and social welfare systems worldwide. In order to slow the infection rates, lockdown has been implemented almost everywhere. Italy, one of the countries most severely affected, entered the “lockdown” on March 8, 2020. Methods The COvid Mental hEalth Trial (COMET) network includes 10 Italian university sites and the National Institute of Health. The whole study has three different phases. The first phase includes an online survey conducted between March and May 2020 in the Italian population. Recruitment took place through email invitation letters, social media, mailing lists of universities, national medical associations, and associations of stakeholders (e.g., associations of users/carers). In order to evaluate the impact of lockdown on depressive, anxiety and stress symptoms, multivariate linear regression models were performed, weighted for the propensity score. Results The final sample consisted of 20,720 participants. Among them, 12.4% of respondents (N = 2,555) reported severe or extremely severe levels of depressive symptoms, 17.6% (N = 3,627) of anxiety symptoms and 41.6% (N = 8,619) reported to feel at least moderately stressed by the situation at the DASS-21. According to the multivariate regression models, the depressive, anxiety and stress symptoms significantly worsened from the week April 9–15 to the week April 30 to May 4 (p

Background: Full functional recovery is defined as a state in which patients are again able to enjoy their usual activities, return to work, and take care of themselves, and it should represent the end goal of treatment in patients with major depressive disorder (MDD). Patients with MDD report many unmet needs, including residual cognitive symptoms, lack of improvement in psychosocial functioning and life satisfaction, even during mood symptom remission. In this paper, we aim to: (a) identify the available assessment tools for evaluating cognitive and psychosocial functioning in patients with MDD; (b) provide an overview of therapeutic options that can improve full functional recovery in MDD also by improving cognitive symptoms.Methods: The relevant databases MEDLINE, ISI Web of Knowledge – Web of Science Index, Cochrane Reviews Library and PsychoINFO were searched for identifying papers on validated tools for the assessment of cognitive and personal functioning in patients with MDD.Results: New assessment tools (such as the THINC-it TOOL, the COBRA, the SCIP-D, and the UPSA-D) have been developed for evaluating the cognitive dysfunction in MDD patients. Adopting these tools in the clinical routine practice is useful to evaluate the improvement in cognitive functioning and, therefore, the achievement of full functioning recovery. The optimal management of patients with MDD include the combination of pharmacological compounds and psychosocial interventions for achieving full functional recovery in patients with MDD.Conclusions: Full functional recovery must be the target of any treatment programme for patients with MDD. In order to achieve this goal, it is necessary to develop personalized treatment and integrate psychosocial and psychopharmacological interventions.

Bipolar disorder (BD) is a common, highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. Lithium is the best-established long-term treatment for BD, even though individual response is highly variable. Evidence suggests that some of this variability has a genetic basis. This is supported by the largest genome-wide association study (GWAS) of lithium response to date conducted by the International Consortium on Lithium Genetics (ConLiGen). Recently, we performed the first genome-wide analysis of the involvement of miRNAs in BD and identified nine BD-associated miRNAs. However, it is unknown whether these miRNAs are also associated with lithium response in BD. In the present study, we therefore tested whether common variants at these nine candidate miRNAs contribute to the variance in lithium response in BD. Furthermore, we systematically analyzed whether any other miRNA in the genome is implicated in the response to lithium. For this purpose, we performed gene-based tests for all known miRNA coding genes in the ConLiGen GWAS dataset (n = 2,563 patients) using a set-based testing approach adapted from the versatile gene-based test for GWAS (VEGAS2). In the candidate approach, miR-499a showed a nominally significant association with lithium response, providing some evidence for involvement in both development and treatment of BD. In the genome-wide miRNA analysis, 71 miRNAs showed nominally significant associations with the dichotomous phenotype and 106 with the continuous trait for treatment response. A total of 15 miRNAs revealed nominal significance in both phenotypes with miR-633 showing the strongest association with the continuous trait (p = 9.80E-04) and miR-607 with the dichotomous phenotype (p = 5.79E-04). No association between miRNAs and treatment response to lithium in BD in either of the tested conditions withstood multiple testing correction. Given the limited power of our study, the investigation of miRNAs in larger GWAS samples of BD and lithium response is warranted.

Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.