Search

Introduction Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology (Mataix-Cols et al., 2005), course (Tukel et al., 2007), and comorbidities (Mahasuar et al., 2011). Early-onset OCD could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression (Park et al., 2022). Objectives The aim of the present study is to evaluate the sociodemographic and clinical differences between the early-onset and late-onset subtypes in a large patient cohort. Methods Two hundred and eighty patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO: early-onset, age

Introduction Medication adherence was defined by the WHO as “the extent to which a person’s behavior coincides with the medical advice given” (WHO, 2003). Existing literature indicates that approximately 49% of patients with major psychiatric disorders do not fully adhere to their prescribed psychopharmacological therapy (Colom et al, 2002). Non-adherence can lead to partial therapeutic responses or treatment resistance, increased risk of relapse, re-hospitalization, elevated suicide risk, and overall poorer functioning, thereby compromising the patient-doctor therapeutic relationship (Garcìa et al, 2016). Objectives The aim of the present study was to assess potential differences in terms of clinical features related to adherence to treatment in a large cohort of psychiatric patients of an Italian psychiatric department. Methods The study included 307 psychiatric patients, of any gender or age, diagnosed with unipolar depression (UD), bipolar depression (BD), anxiety disorders (AD), schizophrenic spectrum disorders (SS) or a primary diagnosis of personality disorders (PD), based on DSM-5 criteria. Patients were consecutively recruited from the Department of Psychiatry at Luigi Sacco University Hospital, in Milan. The patient’s adherence to treatment was evaluated using the Clinician Rating Scale (CRS), with a cut-off of ≥ 5 defining adherence subgroups (A+: score ≥ 5; A-: score < 5). Comparative and predictive analysis were performed for the whole sample and the two adherence subgroups. Results Overall, nearly one-third of the whole sample reported suboptimal medication adherence. Specifically, rates were approximately 35.3% and 32.7% for BD and SS, respectively, followed by 30.8% for PD, 28% for AD and, 20.3% for UD (see Figure 1). Patients with A- showed significantly higher current substance abuse (17.8% vs 4.5%, p

Introduction People with mental illness are overrepresented throughout the criminal justice system. In Italy, an ongoing process of deinstitutionalization has been enacted: the Judicial Psychiatric Hospitals are now on the edge of their closure in favor of small-scale therapeutic facilities (Residenze per l’Esecuzione delle Misure di Sicurezza - REMS). Law 81/2014 prescribes that a patient cannot stay in a REMS for a period longer than a prison sentence for the same index offense. Therefore, when patients end their duty for criminal behaviors, their clinical management moves back to outpatient psychiatric centers. Elevated risks of violent behavior are not equally shared across the spectrum of psychiatric disorders. In the past several years, multiple studies in the field of forensic psychiatry confirmed a close relationship between violent offenders and comorbid substance abuse. Objectives In order to broaden the research in this area, we analyzed sociodemographic, clinical and forensic variables of a group of psychiatric patients with a history of criminal behaviors, attending an outpatient psychiatric service in Milan, with a focus on substance abuse. Methods This is a cross-sectional single center study, conducted in 2020. Seventy-six subjects with a history of criminal behaviors aged 18 years or more and attending an outpatient psychiatric service were included. Demographic and clinical variables collected during clinical interviews with patients were retrospectively retrieved from patients’ medical records. Appropriate statistical analyses for categorical and continuous variables were conducted. Results Data were available for 76 patients, 51,3% of them had lifetime substance abuse. Lifetime substance abuse was significantly more common in patients with long-acting injectable antipsychotics therapy, >3 psychiatric hospitalizations, history of previous crimes and economic crime (Table 1). Additionally, this last potential correlation was confirmed by logistic regression. Table 1. Lifetime substance abusers (N=39) Non-lifetime substance abusers (N=37) Proportion Difference P-value N % N % Depot administration Yes 11 (28,9%) 0 (0%) 28,9% 0,02 Hospitalizations Four or more 25 (64,1%) 5 (33,3%) 30,8% 0,04 Economic crime Yes 15 (40,5%) 1 (6,7%) 33,8% 0,02 Previous crimes Yes 17 (51,4%) 2 (13,3%) 38,1% 0,02 Conclusions Data emerging from this survey provide new information about offenders in an Italian mental health service with a focus on lifetime substance abuse in these patients. Our preliminary results should be confirmed in larger sample sizes. Disclosure of Interest None Declared

Introduction Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment and rTMS protocols have been included in international guidelines for patients with treatment-resistant depression (TRD). The daily administration of standard rTMS protocols, typically over several weeks, could be a limiting factor (e.g., time off from work, commuting issues). To intensify the antidepressant response and to reduce the number of stimulation days, it has been proposed that increasing the number of rTMS sessions performed per day could be more effective and help to reduce the burden for patients and clinicians. Although there is much interest in accelerated TMS protocols, little is known about their efficacy and tolerability, and the literature on the topic is still scarce. Objectives To compare the efficacy and tolerability of two rTMS protocols (standard vs. accelerated) as augmentative strategies in patients with TRD. Methods In the present ongoing, open-label, trial 14 patients meeting DSM-5 criteria for major depressive episode (either unipolar or bipolar), classified as partial responders or non-responders to adequate pharmacological treatment, were randomized to receive either standard (one session per day, five days a week, for four weeks; n= 7) or accelerated (two sessions per day, five days a week, for two weeks; n=6) rTMS treatment protocols. In both cases, rTMS was performed on the left dorsolateral prefrontal cortex, high frequency (10 Hz) at 120% of the motor threshold, 3000 pulses per sessions. Primary outcome measures included HAM-D, MADRS, and CGI-S scores at baseline (T0), at the end of rTMS treatment (T1), and after 1 month (T2), as well as tolerability based on adverse effects. Paired Samples t-Test for continuous variables was used to compare psychometric scales at each timepoint, while t-Test was used to compare differences between the two groups. Results With respect to total sample, in terms of primary outcome measures a significant reduction of HAM-D, MADRS and CGI-S total scores between T0 and T1 (t: 3.01, p

Introduction Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence. Objectives Aim of the present study was to assess potential differences in terms of clinical and socio-demographic characteristics specifically related to adherence to treatment features, medical comorbidities, and substance abuse in a sample of patients diagnosed with Major Depression in an Italian psychiatric department. Methods Patients with a DSM-5 diagnosis of Unipolar or Bipolar Major Depressive Episode, of either gender or any age were recruited from the Psychiatry Department of Luigi Sacco University Hospital in Milan. Main clinical and socio-demographic variables were collected reviewing patients’ medical records. Moreover, adherence to psychopharmacological treatment was assessed using the Clinician Rating Scale (CRS; Kemp et al, 1996; 1998). Adherence was defined as ratings of > or =5 on the CRS. Descriptive and association analyzes were performed, setting the significance level at p

Introduction Obsessive Compulsive Disorder (OCD) and Tic Disorder (TD) are two highly disabling, comorbid and difficult-to-treat conditions. DSM-5 acknowledged a new “tic-related” specifier for OCD, i.e., Obsessive-Compulsive Tic-related Disorder (OCTD), which may show poor treatment response. Objectives The aim of the present study was to evaluate rates and clinical correlates of response, remission and resistance to treatment in a large multicentre sample of OCD patients with versus without tics. Methods 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from ten psychiatric departments across Italy. Treatment response profiles in the whole sample were analysed comparing the rates of response, remission and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to highlight possible treatment response related factors. Results Later ages of onset of TD and OCD were found in the remission group. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts were associated to the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement. Conclusions While remission was related to later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response, with a significant impairment in quality of life for both patients and their caregivers. These findings suggest a worse profile of treatment response for patients with OCTD. Disclosure No significant relationships.

Introduction Non adherence to psychotropic drugs is associated with negative outcomes, including hospitalizations, aggressive behaviors, suicide attempts and increased premature mortality. It represents a psychiatric challenge, especially in young adults who show higher risk of non-adherence to treatment Objectives Firstly this study evaluates the incidence of non-adherence to therapy in 18-24 years patients from a Psycho-Social Center in Milan; and then to analyze the predictive factors of non-adherence. Methods In this retrospective “Real Life” observational study, 120 outpatients aged 18 to 24 years, from Psycho-social Center of L. Sacco University Hospital in Milan, were recruited in 2019. Non-adherence to treatment, according to the World Health Organization, was considered “a modality of assuming medications that does not correspond to healthcare professionals’ recommendations”. Statistical analysis were performed with chi-square, ANOVA and linear regression tests, setting significance to p

Objective: This study aimed to investigate the influence of periodontal status, clinical data, and serum markers on salivary leptin levels in patients with systemic lupus erythematosus (SLE). Methods: A case–control study was conducted with 38 patients with SLE and 29 healthy controls. Periodontal data included periodontal probing depth (PPD), clinical attachment level (CAL), and gingival bleeding on probing (BOP). Stimulated saliva samples were collected to analyze salivary leptin levels. Clinical and serum data were collected from the SLE group. Statistical analysis included the t-test, Mann–Whitney test, Spearman correlation coefficient, and a structural equation model. Results: The SLE group had a lower salivary leptin level than the control group (P = 0.002). The model revealed that SLE had an inverse and independent effect on salivary leptin (standardized estimate = − 0.289, P = 0.023). Moreover, salivary leptin level negatively correlated with the serum levels of triglyceride, creatinine, and leukocytes, positively correlated with the serum total cholesterol, but was not significantly correlated with the periodontal status. Conclusion: These findings suggest that patients with SLE have a lower salivary leptin level. In addition, the level of salivary leptin does not appear to be related to periodontal status in patients with SLE.

Obsessive-compulsive disorder (OCD) is a chronic illness associated with significant functional impairment. Monotherapy with serotonin reuptake inhibitors (SRIs) often leads to only partial improvement of symptoms. In such cases, a common, well established, treatment approach for most patients is the augmentation of SRI therapy with antipsychotic medications. Brexpiprazole is an atypical antipsychotic agent that acts as a partial agonist of 5-HT1A, D2, and D3 receptors. Purpose of this retrospective observational study was to evaluate the effectiveness and tolerability of brexpiprazole as augmentation to SRIs in patients with treatment-resistant OCD. This preliminary study included a sample of 10 patients diagnosed with treatment-resistant OCD who underwent a 12-week trial of augmentative brexpiprazole, starting at a dose of 1 mg/day, with dosage adjustments based on clinical judgment. Treatment response was assessed through changes in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score from baseline to the end of the 12-week observation period. Adverse events were systematically recorded. Significant improvement was observed after the 12-week period: at the endpoint, seven patients (70%) achieved a ≥25% reduction in Y-BOCS total score compared to baseline, with five of them (50% of the overall sample) showing a more robust clinical response (≥35% reduction). Mild adverse effects, such as sedation and weight gain, were reported by two participants (20% of the overall sample). These findings suggest that brexpiprazole may offer a promising effectiveness and tolerability profile in the management of treatment-resistant OCD., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Even though the COVID-19 emergency has concluded, its consequences are still relevant. Recent evidence suggests that a significant proportion of individuals experience persistent symptoms long after the initial infection has resolved, classified as "Long COVID" condition. Fear of COVID-19 increases anxiety and stress levels in healthy individuals and exacerbates the symptoms of those with pre-existing psychiatric disorders; therefore understanding the impact of the pandemic on psychiatric disorders remains of utmost importance. The present study aimed at assessing the prevalence and predictive factors of fear of COVID-19 in a sample of patients with different psychiatric conditions., Method: A sample of 269 psychiatric patients were recruited from two different tertiary clinics in Italy and assessed with the Fear of COVID-19 Scale (FCV-19S). In order to compare patients with a significant fear of COVID-19 or without (Fear+ vs. Fear-) and to identify the main features in terms of clinical dimension, exploratory and predictive analysis were performed., Results: Female gender, age at illness onset, and insight levels emerged as positive predictors of FCV-19S. Conversely, current substance abuse emerged as a negative predictor of fear levels. Moreover, significantly lower FCV-19S scores were observed in patients with a diagnosis of schizophrenia spectrum disorders., Conclusions: Specific sociodemographic and clinical factors predicted higher levels of fear of COVID-19 in psychiatric patients. Further studies are warranted to determine the potential long-term consequences of the COVID-19 impact on mental health., Competing Interests: Competing interests: None., (© 2024 Giovanni Fioriti Editore s.r.l.)

Background/objectives: In the past two decades, significant advancements in neuromodulation techniques have occurred, such as transcranial magnetic stimulation (TMS) for treatment-resistant depression (TRD). According to the assumption that repeated stimulation within a condensed timeframe can yield sustained efficacy, an accelerated protocol may be more effective in reducing time to response. With those premises, this study aimed to evaluate a sample of TRD patients treated with standard repetitive TMS (rTMS) and accelerated rTMS (arTMS)., Methods: Nine subjects were treated with standard rTMS and 19 with arTMS. Psychometric assessment was made at the baseline and one week, one month, and three months after the treatment. A linear mixed-effect regression was performed along with other appropriate statistical analyses., Results: A significant improvement over time was observed for both depressive and cognitive symptoms. Moreover, considering the reduction in the Montgomery-Asberg Depression Rating Scale scores, a better treatment response was observed in subjects treated with arTMS ( p < 0.05)., Conclusions: Our findings showed a significant difference between the two protocols in terms of clinical response. Although further studies are needed to confirm the superiority of arTMS, the better cost-effectiveness of this technique should be considered.

Depressive disorders are leading contributors to the global mental health-related burden, and they represent a challenge for real-world clinicians, due to the low rates of remission despite the high availability of treatments. Often, depression shows in the context of multiple chronic comorbidities, thus requiring precise and accurate management of pharmacological treatments to avoid interactions and side effects. These criticalities call for the need for new strategies of treatment, which may include new insights into the pharmacological properties of currently available antidepressant drugs, to enhance their efficacy in the different contexts in which depression may arise. Trazodone is the prototype serotonin antagonist/reuptake inhibitor antidepressant (SARI). Due to the malleability granted by its multiple formulations, trazodone is frequently used to treat depression, both as an add-on to other antidepressants and as a monotherapy, with satisfying results. Moreover, its tolerability makes it one of the most prescribed antidepressants in patients with poly-treated comorbid medical illnesses, especially in the elderly. Herein, a case series is presented regarding the use of trazodone in patients with complex comorbid diagnoses or distressing side effects. Each of the three cases has been discussed in three specific Round Tables, involving expert clinicians in the fields of Psychiatry, Neurology, General Practice, and Geriatrics using the Nominal Group Technique. The ideas collected have been used to integrate the cases and the discussion with the intent of facilitating accessibility to the widest audience of physicians and clinical workers in different clinical practice contexts. The final aim of this paper is to promote an increasingly personalized use of trazodone in real-world patients with depression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. The authors declare that this study received funding from Angelini Pharma. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication., (Copyright © 2024 Rosso, Benatti, Pettorruso, Sampogna and Tomasetti.)

During the COVID-19 pandemic, a significant rise in mental health issues was observed. Particularly, children and adolescents have shown a higher risk of developing mental disorders than adults. This study aimed to describe the evolving features of the requests for psychiatric emergency interventions during the COVID-19 pandemic in young people. We conducted a cross-sectional study comparing the number, characteristics, and symptoms of people aged between 12 and 18 years old attending one Emergency Department (ED) for psychiatric issues, considering three different periods: T0 (8 March 2019-7 March 2020), T1 (8 March 2020-7 March 2021), and T2 (8 March 2021-7 March 2022). Total admissions were 220: 99 (45%) during T0, 40 (18.1%) for T1, and 81 (36.8%) for T2 ( P  < 0.001). A significant decrease in the mean age from T0 to T1 was found ( P  < 0.01). Admissions for psychomotor agitation decreased, while admission due to anxiety disorder and nonsuicidal self-injury raised significantly ( P  < 0.05), as for first psychiatric presentation ( P  < 0.01). Regarding substance use, a significant reduction was observed ( P  < 0.05). The rates of eating disorders ( P  < 0.001) and early insomnia ( P  < 0.01) increased from T0. These findings highlight the worsening of psychiatric symptoms in the young population during the COVID-19 pandemic., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Although gender-specific evidence on Gambling Disorder (GD) is still limited, some studies reported specific differences, mainly in psychopathological profiles, gambling behavior patterns, and pathogenesis. In order to further examine the role of gender in GD, we conducted a multicenter investigation in a sample of Italian outpatients., Method: One hundred-four outpatients with a diagnosis of GD based on DSM-5 criteria were consecutively recruited at two clinics based in Milan. Socio-demographic and clinical variables were collected for the whole sample and analyzed for the effect of gender. The severity of illness was assessed using the Canadian Problem Gambling Index and the Gambling Attitudes and Beliefs (GABS)., Results: Among females, a significantly higher mean age (52.23 ± 10.95 vs. 40.96 ± 15.76; p=0.005) and older age at illness onset emerged (43.5 ± 11.92 vs. 29.22 ± 14.26; p<0.001). Females showed a significantly higher rate of psychiatric comorbidities, lifetime suicide ideation, stressful events at GD onset, and positive family history for GD compared to males. A predictive effect of male gender was found for the GABS questionnaires by performing a linear regression model, with males showing a higher risk to reach higher scores compared to females (B= 11.833; t=2.177; p=0.034)., Conclusions: Our study seems to confirm the hypotheses that gender in GD may influence psychopathological profiles, course, and comorbidity. GD in female gender is frequently a comorbid condition with other specific clinical characteristics compared to males. Identifying specific clinical factors by gender may prompt more focus on the public health of women in relation to gambling, while still recognizing that males are at-risk of earlier gambling problems. These findings should be considered in therapeutic perspectives., Competing Interests: Competing interests: Prof. Dell’Osso has received Grant/Research Support from LivaNova, Inc., Angelini, and Lundbeck, and Lecture Honoraria from Angelini, Janssen, Otzuka, and Lundbeck, Viatris and Bromatech. Dr. Benatti has received lecture honoraria from Angelini, Lundbeck, Janssen, Rovi. Dr. Percudani has received Grant/Research Support from Janssen, Otsuka, Lundbeck e Angelini. Drs. Girone, Limosani, Ciliberti, Turco, Longo, Colletti, Cocchi, Zita, Fiocchi, Viganò have nothing to declare.., (© 2024 Giovanni Fioriti Editore s.r.l.)

Treatment-Resistant Depression (TRD) poses a substantial health and economic challenge, persisting as a major concern despite decades of extensive research into novel treatment modalities. The considerable heterogeneity in TRD's clinical manifestations and neurobiological bases has complicated efforts toward effective interventions. Recognizing the need for precise biomarkers to guide treatment choices in TRD, herein we introduce the SelecTool Project. This initiative focuses on developing (WorkPlane 1/WP1) and conducting preliminary validation (WorkPlane 2/WP2) of a computational tool (SelecTool) that integrates clinical data, neurophysiological (EEG) and peripheral (blood sample) biomarkers through a machine-learning framework designed to optimize TRD treatment protocols. The SelecTool project aims to enhance clinical decision-making by enabling the selection of personalized interventions. It leverages multi-modal data analysis to navigate treatment choices towards two validated therapeutic options for TRD: esketamine nasal spray (ESK-NS) and accelerated repetitive Transcranial Magnetic Stimulation (arTMS). In WP1, 100 subjects with TRD will be randomized to receive either ESK-NS or arTMS, with comprehensive evaluations encompassing neurophysiological (EEG), clinical (psychometric scales), and peripheral (blood samples) assessments both at baseline (T0) and one month post-treatment initiation (T1). WP2 will utilize the data collected in WP1 to train the SelecTool algorithm, followed by its application in a second, out-of-sample cohort of 20 TRD subjects, assigning treatments based on the tool's recommendations. Ultimately, this research seeks to revolutionize the treatment of TRD by employing advanced machine learning strategies and thorough data analysis, aimed at unraveling the complex neurobiological landscape of depression. This effort is expected to provide pivotal insights that will promote the development of more effective and individually tailored treatment strategies, thus addressing a significant void in current TRD management and potentially reducing its profound societal and economic burdens., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Pettorruso, Di Lorenzo, Benatti, d’Andrea, Cavallotto, Carullo, Mancusi, Di Marco, Mammarella, D’Attilio, Barlocci, Rosa, Cocco, Padula, Bubbico, Perrucci, Guidotti, D’Andrea, Marzetti, Zoratto, Dell’Osso and Martinotti.)

Objective: People with mental illness are overrepresented throughout the criminal justice system. In Italy, the Judicial Psychiatric Hospitals are now on the edge of their closure in favor of small-scale therapeutic facilities (REMS). Therefore, when patients end their duty for criminal behaviors, their clinical management moves back to the outpatient psychiatric centers. Elevated risks of rule-violating behavior are not equally shared across the spectrum of psychiatric disorders. To broaden the research in this area, we analyzed sociodemographic, clinical, and forensic variables of a group of psychiatric patients with a history of criminal behaviors, attending an outpatient psychiatric service in Milan, focusing on substance use disorder (SUD)., Methods: This is a cross-sectional single center study, conducted from 2020. Seventy-six subjects with a history of criminal behaviors aged 18 years or older and attending an outpatient psychiatric service were included. Demographic and clinical variables collected during clinical interviews with patients were retrospectively retrieved from patients' medical records. Appropriate statistical analyses for categorical and continuous variables were conducted., Results: Data were available for 76 patients, 51.3% of them had lifetime SUD. Lifetime SUD was significantly more common in patients with long-acting injectable antipsychotics therapy, a history of more than 3 psychiatric hospitalizations, and a history of previous crimes, particularly economic crimes. Additionally, this last potential correlation was confirmed by logistic regression., Conclusions: Data emerging from this survey provide new information about offenders with lifetime SUD attending an Italian mental health service. Our preliminary results should be confirmed in larger sample sizes.

Interoception is defined as the sense of the internal state of the body. Dysfunctions in interoception are found in several mental disorders, including trauma-related conditions. Mindfulness-Based Interventions (MBIs) have been shown to influence interoceptive processes. Randomised controlled trials (RCTs) have investigated whether MBIs impact symptoms and interoception in patients with trauma-related disorders. We undertook a systematic review and meta-analysis to synthesize these data. We included RCTs with an MBI arm which enrolled adult patients with trauma related-disorders or exposure to a traumatic experience, and addressed changes in interoception and trauma-related symptoms. A random-effects multivariate meta-analytic model was performed to quantify group differences in score change from baseline to follow-up. Twelve studies were included in the systematic review, and eleven in the meta-analysis. Overall, MBIs showed small to moderate positive effects on both interoception and symptoms. Despite a high heterogeneity in results, sensitivity analyses confirmed the robustness of the findings. We conclude that the efficacy of MBIs on trauma-related symptoms and interoception is supported by randomised evidence. However, further research is needed to understand whether changes in interoception might underpin the effectiveness of MBIs in trauma-related disorders., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Baldwin is a Medical Patron of Anxiety UK, and a co-applicant in an NIHR-funded study of EMDR for post-traumatic symptoms following intensive care unit admissions. Prof. Dell'Osso has received Grant /Research Support from LivaNova, Inc., Angelini, and Lundbeck, and Lecture Honoraria from Angelini, Janssen, Otzuka, and Lundbeck, outside the present work. Dr. Benatti has received consultant fee for Lundbeck. Dr Huneke is an NIHR Academic Clinical Lecturer. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR, NHS or the UK Department of Health and Social Care., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Approximately 50% of patients with psychiatric disorders do not fully adhere to the prescribed psychopharmacological therapy, significantly impacting the progression of the disorder and the patient's quality of life. The present study aimed to assess potential differences in terms of rates and clinical features of treatment adherence in a large cohort of psychiatric patients with different diagnoses attending various psychiatric services. The study included 307 psychiatric patients diagnosed with a primary major depressive disorder, bipolar disorder, anxiety disorder, schizophrenic spectrum disorder, or personality disorder. Patient's adherence to treatment was evaluated using the Clinician Rating Scale, with a cutoff of at least five defining adherence subgroups. One-third of the sample reported poor medication adherence. A lower rate of adherence emerged among patients with schizophrenic spectrum disorder and bipolar disorder. Subjects with poor adherence were more frequently inpatients and showed higher current substance use, a greater number of previous hospitalizations, and more severe scores at psychopathological assessment compared with patients with positive adherence. Poor adherence was associated with symptom severity and increased rates of relapses and rehospitalizations. In addition, substance use appears to be an unfavorable transdiagnostic factor for treatment adherence., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions.

Introduction: Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology, course, and comorbidities. Early-onset OCD (EO) could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression. To deepen the heterogeneous nature of the disorder, we analyzed sociodemographic and clinical differences between the EO and late-onset (LO) subtypes in a large outpatient cohort., Methods: Two hundred and eighty-four patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO, age <18 years [n = 117,41.2 %]; LO: late-onset, age ≥18 years [n = 167, 58.8 %])., Results: The EO group showed a higher frequency of male gender (65 % vs 42.5 %, p < .001), and a higher prevalence of Tic and Tourette disorders (9.4 % vs 0 %, p < .001) compared to the LO group. Additionally, in the EO subgroup, a longer duration of untreated illness was observed (9.01 ± 9.88 vs 4.81 ± 7.12; p < .001), along with a lower presence of insight (13.8 % vs. 7.5 %, p < .05)., Conclusions: The early-onset OCD subtype highlights a more severe clinical profile compared to the LO group. Exploring distinct manifestations and developmental trajectories of OCD can contribute to a better definition of homogeneous subtypes, useful for defining targeted therapeutic strategies for treatment., Competing Interests: Declaration of competing interest In the last three years, Prof. Dell’Osso has received lecture honoraria and grants from Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova. In the last three years, Dr Benatti has received lecture honoraria from Angelini, Lundbeck, Janssen, Rovi. The other authors have no conflicts to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in the world. The neurobiology of OCD has not been completely understood and efforts are needed in order to develop new treatments. Beside the classical neurotransmitter systems and signalling pathways implicated in OCD, the possible involvement of the endocannabinoid system (ECS) has emerged in pathophysiology of OCD. We report here selective downregulation of the genes coding for enzymes allowing the synthesis of the endocannabinoids. We found reduced DAGLα and NAPE-PLD in blood samples of individuals with OCD (when compared to healthy controls) as well as in the amygdala complex and prefrontal cortex of dopamine transporter (DAT) heterozygous rats, manifesting compulsive behaviours. Also mRNA levels of the genes coding for cannabinoid receptors type 1 and type 2 resulted downregulated, respectively in the rat amygdala and in human blood. Moreover, NAPE-PLD changes in gene expression resulted to be associated with an increase in DNA methylation at gene promoter, and the modulation of this gene in OCD appears to be correlated to the progression of the disease. Finally, the alterations observed in ECS genes expression appears to be correlated with the modulation in oxytocin receptor gene expression, consistently with what recently reported. Overall, we confirm here a role for ECS in OCD at both preclinical and clinical level. Many potential biomarkers are suggested among its components, in particular NAPE-PLD, that might be of help for a prompt and clear diagnosis., (© 2024. The Author(s).)

Background: Bipolar disorder (BD) and obsessive-compulsive disorder (OCD) comorbidity is an emerging condition in psychiatry, with relevant nosological, clinical, and therapeutic implications., Methods: We updated our previous systematic review on epidemiology and standard diagnostic validators (including phenomenology, course of illness, heredity, biological markers, and treatment response) of BD-OCD. Relevant papers published until (and including) 15 October 2023 were identified by searching the electronic databases MEDLINE, Embase, PsychINFO, and Cochrane Library, according to the PRISMA statement (PROSPERO registration number, CRD42021267685)., Results: We identified 38 new articles, which added to the previous 64 and raised the total to 102. The lifetime comorbidity prevalence ranged from 0.26 to 27.8% for BD and from 0.3 to 53.3% for OCD. The onset of the two disorders appears to be often overlapping, although the appearance of the primary disorder may influence the outcome. Compared to a single diagnosis, BD-OCD exhibited a distinct pattern of OC symptoms typically following an episodic course, occurring in up to 75% of cases (vs. 3%). Notably, these OC symptoms tended to worsen during depressive episodes (78%) and improve during manic or hypomanic episodes (64%). Similarly, a BD course appears to be chronic in individuals with BD-OCD in comparison to patients without. Additionally, individuals with BD-OCD comorbidity experienced more depressive episodes (mean of 8.9 ± 4.2) compared to those without comorbidity (mean of 4.1 ± 2.7)., Conclusions: We found a greater likelihood of antidepressant-induced manic/hypomanic episodes (60% vs. 4.1%), and mood stabilizers with antipsychotic add-ons emerging as a preferred treatment. In line with our previous work, BD-OCD comorbidity encompasses a condition of greater nosological and clinical complexity than individual disorders.

Obsessive-compulsive disorder (OCD) is a prevalent and highly disabling condition, characterized by a range of phenotypic expressions, potentially associated with geo-cultural differences. This article aims to provide an overview of the published studies by the International College of Obsessive-Compulsive Spectrum Disorders, in relation to the Snapshot database which has, over the past 10 years, gathered clinical naturalistic data from over 500 patients with OCD attending various research centers/clinics worldwide. This collaborative effort has provided a multi-cultural worldwide perspective of different socio-demographic and clinical features of patients with OCD. Data on age, gender, smoking habits, age at onset, duration of illness, comorbidity, suicidal behaviors, and pharmacological treatment strategies are presented here, showing peculiar differences across countries.

Climate change is one of the main global challenges and influences various aspects of human health. Numerous studies have indeed demonstrated an association between extreme climate-related events and physical and mental health outcomes, but little is still known about the association between the perception/awareness of climate change and mental health. In accordance with the PRISMA 2020 guidelines, a search was conducted on PubMed and Scopus. The protocol was registered on PROSPERO. The included studies were original observational studies published in English, reporting the association between the perception/awareness of climate change and mental health. A total of 3018 articles were identified. A total of 10 observational studies were included. The period covered in the included studies ranged between 2012 and 2022. Climate change perception is consistently associated with adverse mental health effects across different types of estimates. In particular, the studies identified an association between a higher level of perception/awareness of climate change and depression, anxiety, eco-anxiety, stress, adjustment disorder, substance use, dysphoria, and even thoughts of suicide. Qualitative data underscore the impact on daily activities, contributing to feelings of loss and suicidal ideation. Moreover, climate change perception correlates with lower well-being and resilience. The association between awareness of climate change and mental health is a complex and still poorly explored phenomenon. The main limitations are the high heterogeneity in terms of exposure assessment and data reporting, which hinders quantitative analysis. These results show that climate change perception impacts mental health. Better understanding the phenomenon represents an opportunity to inform public health interventions that promote mental well-being.

The potentially problematic use of the Internet is a growing concern worldwide, which causes and consequences are not completely understood yet. The neurobiology of Internet addiction (IA) has attracted much attention in scientific research, which is now focusing on identifying measurable biological markers. Aim of this study was to investigate epigenetic and genetic regulation of oxytocin receptor (OXTR), dopamine transporter (DAT1) and serotonin transporter (SERT) genes using DNA obtained from saliva samples of young university students: the Internet Addiction Test (IAT) was administered to evaluate the potential existence and intensity of IA. Significant changes in DNA methylation levels at OXTR, DAT1 and SERT genes were observed in the 30 < IAT < 49 group (mild-risk internet users) compared to the IAT < 29 subjects (complete control of internet use) and IAT > 50 subjects (considered as moderately addicted). Moreover, epigenetic markers were significantly correlated, either directly (for OXTR and DAT1) or inversely (OXTR and DAT1 versus SERT), to the psychometric properties. Our data confirmed the association of OXTR, DAT1 and SERT genes in processes related to behavioural addictions and might be of relevance to suggest possible biological predictors of altered behaviours and the eventual vulnerability to develop an IA. Different other genetic pathways have been suggested to play a role in IA and research is ongoing to better define them, in order to help in the early diagnosis as well as in the development of new potential treatments., (© 2023. The Author(s).)

Objective: Limited studies have investigated cannabis use in patients with obsessive-compulsive disorder (OCD), despite its widespread use by patients with psychiatric illnesses. The aim of this study was to assess the frequency, correlates, and clinical impact of cannabis use in an Italian sample of patients with OCD., Methods: Seventy consecutive outpatients with OCD were recruited from a tertiary specialized clinic. To assess cannabis-related variables, patients completed a questionnaire developed for the purpose of this study, investigating cannabis use-related habits and the influence of cannabis use on OCD symptoms and treatments. A set of clinician and self-reported questionnaires was administered to measure disease severity. The sample was then divided into three subgroups according to the pattern of cannabis use: "current users" (CUs), "past-users" (PUs), and "non-users" (NUs)., Results: Approximately 42.8% of patients reported lifetime cannabis use and 14.3% reported current use. Approximately 10% of cannabis users reported an improvement in OCD symptoms secondary to cannabis use, while 23.3% reported an exacerbation of anxiety symptoms. CUs showed specific unfavorable clinical variables compared to PUs and NUs: a significant higher rate of lifetime use of tobacco, alcohol, and other substances, and a higher rate of pre-OCD onset comorbidities. Conversely, the three subgroups showed a similar severity of illness., Conclusion: A considerable subgroup of patients with OCD showed a predisposition towards cannabis use and was associated with some specific clinical characteristics, suggesting the need for targeted consideration and interventions in this population.

Obsessive Compulsive Disorder (OCD) is a mental health condition still classified and diagnosed with subjective interview-based assessments and which molecular clues have not completely been elucidated. We have recently identified a new regulator of anxiety and OCD-like behavior called Immuno-moodulin (IMOOD) and, here, we report that IMOOD gene promoter is differentially methylated in OCD subjects when compared to genomic material collected from healthy controls and this alteration is significantly correlated with the increased expression of the gene in OCD. We also demonstrated that IMOOD promoter can form G-quadruplexes and we suggest that, in homeostatic conditions, these structures could evoke DNA-methylation silencing the gene, whereas in pathological conditions, like OCD, could induce gene expression making the promoter more accessible to transcriptional factors. We here thus further suggest IMOOD as a new biomarker for OCD and also hypothesize new mechanisms of gene regulation., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis., Methods: We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated., Results: A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia., Conclusion: Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs., Competing Interests: BD’O has received lecture honoraria that are not related to the work submitted for publication, from Angelini, Janssen, Lundbeck, Bromatech, Otzuka, and Neuraxpharm. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Battini, Cirnigliaro, Leuzzi, Rissotto, Mosini, Benatti, Pozzi, Nobile, Radice, Carnovale, Dell’Osso and Clementi.)

Objective: Depression represents one of the most severe psychiatric disorders, characterized by low mood episodes, as well as loss of interest. Major Depressive Episodes (MDE) treatment relies primarily on monoaminergic prescriptions. However, although the presence of many antidepressant medications, their efficacy is still partial. A promising intervention to improve antidepressant treatment may be the use of adjunctive nutraceuticals. Aim of the present study was to assess the efficacy of a N-Acetyl-cysteine, S-Adenosyl-L-Methionine and Folic acid's combination for the treatment of depressive symptoms in a sample of MDE patients., Method: Fifty outpatients with a MDE diagnosis in the context of different psychiatric disorders such as Major Depression, Bipolar Disorder, Anxiety disorders, and Personality disorders were recruited. The sample was divided into different groups based on the nutraceutical administration: a) concurrently with an AD (starter group); b) add-on to an already prescribed treatment; c) single treatment., Results: A significant reduction of CGI-Severity and Improvement scores from baseline to the end of treatment was found. Moreover, the starter group showed a significantly greater CGI-Improvement score compared to the other groups. Ninety-four percent of patients did not show any side effects., Conclusions: The present study showed promising results for the use of nutraceuticals in the add-on treatment of MDE. Those compounds may be considered a versatile, tolerable, and effective add-on treatment for the reduction of depressive symptoms impact and for improving the functioning of patients affected by MDE., Competing Interests: Competing interests: In the last three years, Prof. Dell’Osso has received lecture honoraria and grants from Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova. Prof. Benatti has received consulting fees from Janssen, Lundback, Angelini and honoraria from Angelini. The other authors have no conflicts to declare., (© 2023 Giovanni Fioriti Editore s.r.l.)

Introduction: Immunoassay urine drug screen (UDS) is frequently used in clinical practice for initial screening process, being generally available, fast, and inexpensive. Exposure to widely prescribed drugs might determine false-positive UDS amphetamines, leading to diagnostic issues, wrong therapeutic choices, impairment of physician-patient relationship, and legal implications., Areas Covered: To summarize and comment on a comprehensive list of compounds responsible for UDS false positives for amphetamines, we conducted a literature review on PubMed along with a comparison with Real-World Data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database analysis between 2010 and 2022. Forty-four articles and 125 Individual Case Safety Reports (ICSR) involving false-positive amphetamine UDS in psychiatric patients were retrieved from FAERS., Expert Opinion: False-positive results were described in literature for antidepressants, atomoxetine, methylphenidate, and antipsychotics, but also for non-psychiatric drugs of common use, such as labetalol, fenofibrate, and metformin. Immunoassay method is usually responsible for false-positive results, and in most cases, mass spectrometry (MS) does not eventually confirm the UDS positivity. Physicians should be aware of immunoassays' limitations and when turning to a confirmatory test. Any new cross-reaction should be reported to pharmacovigilance activities.

Background: Differences based on gender in the presentation and outcome of many psychiatric conditions have been highlighted in the past years. Moreover, women are often underrepresented in research samples, thus leading to a poorer understanding and addressing of their needs. As regards psychiatric rehabilitation, few studies have focused on the influence of gender on the outcomes of rehabilitation programs., Objectives: This study aimed to analyze the impact of gender on socio-demographic and clinical characteristics, as well as on main rehabilitation outcomes, in a sample of subjects undergoing rehabilitation programs in a metropolitan residential service., Methods: We collected socio-demographic, clinical variables and rehabilitation outcomes of all subjects discharged from the metropolitan residential rehabilitative service of the Luigi Sacco Hospital in Milan, Italy, from January 2015 to December 2021. Gender differences were analyzed through t -test and chi-square for continuous and categorical variables, respectively., Results: In a total sample of 129 subjects equally distributed for gender (50.4% women), all subjects improved after their rehabilitation program, as measured through specific psychometric scales. However, women had a higher proportion of discharges to their own household (52.3% vs. 25% of men). They also showed higher educational status (53.8% completed high school vs. 31.3% of men). Clinically, they showed longer duration of untreated illness (3.6 ± 7.31 vs. 1.06 ± 2.35 years) and lower frequency of substance use disorders compared to men (6.4% vs. 35.9%)., Conclusion: The main result of this study shows, in light of an equal improvement in psychopathological and psychosocial functioning after the rehabilitation program, better outcomes in women compared to men, with a higher frequency of return to their own household after the completion of a rehabilitation program compared to men., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cafaro, Rosti, Cerolini, Varinelli, Charitos, Magnotti, Benatti, Dell’Osso and Viganò.)

Objective: health care workers (HCWs) represent a vulnerable group in the COVID-19 pandemic, given the exposure to greater risk and higher levels of work-related stress. Neurofeedback (NF) has shown to be effective in the treatment of stress-related symptoms. We aimed to assess the effectiveness of an alpha-increase NF protocol for the treatment of acute stress symptoms in HCWs exposed to the COVID-19 pandemic., Method: eighteen medical doctors on duty during the COVID-19 health emergency underwent an intensive NF alpha-increase protocol. The mean alpha wave values were recorded at the beginning (T0) and at the last day of stimulation (T1). Rapid Stress Assessment: Italian version; Copenhagen Burnout Inventory (CBI); Pittsburgh Sleep Quality Index (PSQI), and Brief-COPE were administered as psychometric assessment., Results: a significant increase in alpha wave values and a significant reduction of the PSQI scores from T0 to T1 were found., Conclusions: NF alpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement, and safety in a pilot sample of HCWs., Competing Interests: Competing interests: BB has received lecture honoraria from Lundbeck and Janssen. BDO has received lecture honoraria from Angelini, Janssen, Lundbeck, Livanova, Arcapharma, and Neuraxpharm., (© 2023 Giovanni Fioriti Editore s.r.l.)

Introduction: Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence. The aim of the present study is to assess potential differences in terms of clinical and lifestyle features related to adherence to treatment in a sample of patients with unipolar and bipolar depression. Methods: One hundred and eight patients with a diagnosis of unipolar or bipolar depressive episode were recruited from January 2021 to October 2022. Adherence to psychopharmacological treatment was assessed using the clinician rating scale. Descriptive and association analyses were performed to compare subgroups based on adherence to treatment. Results: Lower levels of adherence to treatment were associated with fewer years of education, work impairment, manic prevalent polarity lifetime, and greater comorbidity with alcohol and drug abuse. The majority of patients with positive adherence did not report any hospitalization and involuntary commitment lifetime. Conclusions: Patients with a positive treatment adherence showed significant differences in terms of lifestyle and clinical features compared to non-adherent patients. Our results may help to identify patients more likely to have poor medication adherence, which seem to lead to a worse disease course and quality of life.

Background: Highlighting the relationship between obsessive-compulsive disorder (OCD) and tic disorder (TD), two highly disabling, comorbid, and difficult-to-treat conditions, Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) acknowledged a new "tic-related" specifier for OCD, ie, obsessive-compulsive tic-related disorder (OCTD). As patients with OCTD may frequently show poor treatment response, the aim of this multicenter study was to investigate rates and clinical correlates of response, remission, and treatment resistance in a large multicenter sample of OCD patients with versus without tics., Methods: A sample of 398 patients with a DSM-5 diagnosis of OCD with and without comorbid TD was assessed from 10 different psychiatric departments across Italy. For the purpose of the study, treatment response profiles in the whole sample were analyzed comparing the rates of response, remission, and treatment-resistance as well as related clinical features. Multivariate logistic regressions were performed to identify possible factors associated with treatment response., Results: The remission group was associated with later ages of onset of TD and OCD. Moreover, significantly higher rates of psychiatric comorbidities, TD, and lifetime suicidal ideation and attempts emerged in the treatment-resistant group, with larger degrees of perceived worsened quality of life and family involvement., Conclusions: Although remission was associated with later ages of OCD and TD onset, specific clinical factors, such as early onset and presence of psychiatric comorbidities and concomitant TD, predicted a worse treatment response with a significant impairment in quality of life for both patients and their caregivers, suggesting a worse profile of treatment response for patients with OCTD.

Objective: Cognitive performance in Major Depressive Disorder (MDD) is frequently impaired and related to functional outcomes. Repetitive Transcranial Magnetic Stimulation (rTMS) may exert its effects on MDD acting both on depressive symptoms and neurocognition. Furthermore, cognitive status could predict the therapeutic response of depressive symptoms to rTMS. However, cognitive performances as a predictor of rTMS response in MDD has not been thoroughly investigated. This review aims to evaluate the role of pre-treatment cognitive performance as a predictor of clinical response to rTMS, and the effects of rTMS on neurocognition in MDD., Method: A systematic review of studies evaluating neurocognition in MDD as an outcome and/or predictor of response to rTMS was conducted using PubMed/Medline and Embase., Results: Fifty-eight articles were identified: 25 studies included neurocognition as a predictor of response to rTMS; 56 used cognitive evaluation as an outcome of rTMS. Baseline cognitive performance and cognitive improvements after rTMS predicted clinical response to rTMS. Moreover, rTMS improved cognition in MDD., Conclusions: Cognitive assessment could predict improvement of depression in MDD patients undergoing rTMS and help selecting patients that could have beneficial effects from rTMS. A routine cognitive assessment might stratify MDD patients and track rTMS related cognitive improvement., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest. The current study was conducted with no financial support., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Among patients with mental illness, those with obsessive compulsive disorder (OCD) showed a significant clinical worsening by the COVID-19 pandemic. The effects of the COVID-19 pandemic on OCD have been shown to worsen symptoms severity, with serious clinical consequences. However, the persistence of COVID-19 pandemic in OCD patients has been poorly investigated. The purpose of the present study was to assess the impact of the second wave of the COVID-19 pandemic in a sample of OCD patients and to compare the results with those obtained during the first wave on the same OCD sample., Methods: 116 OCD outpatients attending three OCD tertiary clinics in Northern Italy and previously included in a report on the impact of COVID-19, were followed-up in order to investigate sociodemographic and clinical features. Appropriate statistical analyses for categorical and continuous variables were conducted., Results: The 43 OCD patients with a clinical worsening (OW) reported a significant development of new obsessions/compulsions and the recurrence of past OC symptoms, higher rates of psychiatric comorbidities and sleep disturbances compared to patients without symptom worsening. Moreover, an increase in avoidance behaviors, suicidal ideation, Internet checking for reassurance, and job difficulties emerged in OW patients. Also, lower rates of pharmacological stability, and higher rates of therapy adjustment were observed. In terms of sex differences, males showed higher rates of past obsessions occurrence, while females showed a rise in Internet checking behaviors. When comparing OW patients between the first and the second wave, the latter showed significantly higher rates of past obsession occurrence and lower rates of pharmacological stability. Moreover, patients with OW showed a significantly older age during the second wave., Conclusion: The persistence of the COVID-19 pandemic showed a globally impaired clinical picture in the analyzed OCD sample. A further worsening between the two waves timepoints emerged, mainly involving older patients with OCD. The concordance between our results and those existing in literature highlights the importance of an accurate long-term monitoring of OCD patients in light of COVID-19 pandemic persistence., Competing Interests: Declaration of competing interest Authors have no conflicts of interest to declare in relation to the content of the present article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Global concern about problematic usage of the internet (PUI), and its public health and societal costs, continues to grow, sharpened in focus under the privations of the COVID-19 pandemic. This narrative review reports the expert opinions of members of the largest international network of researchers on PUI in the framework of the European Cooperation in Science and Technology (COST) Action (CA 16207), on the scientific progress made and the critical knowledge gaps remaining to be filled as the term of the Action reaches its conclusion. A key advance has been achieving consensus on the clinical definition of various forms of PUI. Based on the overarching public health principles of protecting individuals and the public from harm and promoting the highest attainable standard of health, the World Health Organisation has introduced several new structured diagnoses into the ICD-11, including gambling disorder, gaming disorder, compulsive sexual behaviour disorder, and other unspecified or specified disorders due to addictive behaviours, alongside naming online activity as a diagnostic specifier. These definitions provide for the first time a sound platform for developing systematic networked research into various forms of PUI at global scale. Progress has also been made in areas such as refining and simplifying some of the available assessment instruments, clarifying the underpinning brain-based and social determinants, and building more empirically based etiological models, as a basis for therapeutic intervention, alongside public engagement initiatives. However, important gaps in our knowledge remain to be tackled. Principal among these include a better understanding of the course and evolution of the PUI-related problems, across different age groups, genders and other specific vulnerable groups, reliable methods for early identification of individuals at risk (before PUI becomes disordered), efficacious preventative and therapeutic interventions and ethical health and social policy changes that adequately safeguard human digital rights. The paper concludes with recommendations for achievable research goals, based on longitudinal analysis of a large multinational cohort co-designed with public stakeholders., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant , promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients-already receiving intranasal ESK but showing an instable course-who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

Introduction: Obsessive-compulsive disorder (OCD) is characterized by a range of phenotypic expressions. Gender may be a relevant factor in mediating the disorder's heterogeneity. The aim of the present report was to explore a large multisite clinical sample of OCD patients, hypothesizing existing demographic, geographical and clinical differences between male and female patients with OCD., Methods: Socio-demographic and clinical variables of 491 adult OCD outpatients recruited in the International College of Obsessive-Compulsive Spectrum Disorders (ICOCS) network were investigated with a retrospective analysis on a previously gathered set of data from eleven countries worldwide. Patients were assessed through structured clinical interviews, the Yale- Brown Obsessive-Compulsive Scale (Y-BOCS), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Self-rating Depression Scale (SDS)., Results: Among females, adult onset (>18 years old) was significantly over-represented (67% vs. 33%, p < 0.005), and females showed a significantly older age at illness onset compared with males (20.85 ± 10.76 vs. 17.71 ± 8.96 years, p < 0.005). Females also had a significantly lower education level than males (13.09 ± 4.02 vs. 13.98 ± 3.85 years; p < 0.05), a significantly higher rate of being married (50.8% vs. 33.5%; p < 0.001) and a higher rate of living with a partner (47.5% vs. 37.6%; p < 0.001) than males. Nonetheless, no significant gender differences emerged in terms of the severity of OCD symptoms nor in the severity of comorbid depressive symptoms. No predictive effect of gender was found for Y-BOCS, MADRS and SDS severity., Discussion/conclusions: Our findings showed significant differences between genders in OCD. A sexually dimorphic pattern of genetic susceptibility may have a crucial role to OCD clinical heterogeneity, potentially requiring different specific therapeutic strategies. Further research is warranted to validate gender as an important determinant of the heterogeneity in OCD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives. This cross-sectional study aimed to investigate the frequency and presentation of cyberchondria (CYB) in patients with obsessive-compulsive disorder (OCD), anxiety disorders (ADs), and major depression disorder (MDD). Methods. Seventy-seven patients (OCD:25, ADs:26, MDD:26) referred to a tertiary psychiatry outpatient clinic and 27 healthy controls (HCs) were included. A 'working' definition of CYB was used to measure CYB frequency. CYB severity was measured with the Cyberchondria Severity Scale (CSS). Results. CYB as currently defined was present in just 1.3% of the combined patients' sample. Using a broader definition (omitting the disability criterion), we found a higher distribution (OCD:12%, ADs:19.2%, MDD:15.4%, HCs:3.7%) and greater CYB symptom severity. Patients with OCD (63.3 ± 18.9) and ADs (63.3 ± 25.9) showed a higher CYB severity, compared with HCs (48.4 ± 9.9, p <.05). In the combined patients' sample, a positive correlation was found between the CSS scores and measures of health anxiety or hypochondriasis. Higher CYB symptom severity emerged in patients with a positive family history of psychiatric disorders and in those prescribed benzodiazepines or mood-stabilisers. Conclusion. CYB represents a common transdiagnostic syndrome in patients with OCD, ADs, and MDD with a spectrum of severity and indicates a variable burden of illness, supporting the need for specific clinical considerations and interventions.Key pointsCyberchondria (CYB) represents a common transdiagnostic syndrome in patients with obsessive-compulsive disorder, anxiety, and depressive disorders.CYB's frequency as a syndrome of compulsive online health searches associated with an increased anxiety and distress was reported in 10-20% patients.Health anxiety/hypochondriasis showed a strong correlation with CYB.Patients with a positive family history of psychiatric disorders and those prescribed benzodiazepines or mood-stabilisers showed higher CYB symptom severity.Considering the spread of Internet use for health-related information, additional studies investigating CYB in clinical samples are encouraged.

Objective: Bupropion, an antidepressant inhibiting the reuptake of dopamine and noradrenaline, should be useful to treat depressive symptoms in patients with Parkinson's disease (PD). Limited and conflicting literature data questioned its effectiveness and safety in depressed PD patients and extended its use to other neuropsychiatric symptoms associated with this disorder., Design: The databases PubMed, Embase, Web of Sciences, Cochrane Library, and the grey literature were searched. Following a scoping review methodology, articles focusing on Bupropion uses in PD patients who manifested depressive or other neuropsychiatric alterations were reviewed., Results: Twenty-three articles were selected, including 7 original articles, 3 systematic reviews or meta-analyses, 11 case reports, 1 clinical guideline, and 1 expert opinion. Bupropion showed considerable effectiveness in reducing depressive symptoms, particularly in relation to apathy. Solitary findings showed a restorative effect on compulsive behaviour secondary to treatment with dopamine as well as on anxiety symptoms. The effect on motor symptoms remains controversial. The safety profile of this medication seems positive, but additional precautions should be used in subjects with psychotic symptoms., Conclusion: The available literature lacks good evidence to support the use of Bupropion in PD patients presenting depressive symptoms. Further investigations are needed to extend and confirm reported findings and to produce accurate clinical guidelines., (© 2022. The Author(s).)

Introduction: Obsessive-compulsive disorder (OCD) is a prevalent and disabling condition with frequent chronic course. Staging models applied to psychiatric disorders seek to define their extent of progression at a particular time-point and differentiate early, milder clinical phenomena from those characterizing illness progression and chronicity. In OCD patients, a staging model has been recently proposed but not tested yet. This was the aim of the present study., Methods: From an overall sample of 198 OCD patients, recruited across two psychiatric clinics in Northern Italy, 70 patients on stable treatment completed a follow-up assessment ranging from 12 to 24 months. At follow-up initiation, patients had been divided into four staging groups, according to the model proposed by Fontenelle and Yucel. At the end of the follow-up, patients were subdivided into three groups (no stage change, improved stage, or worsened stage) compared with statistical analyses., Results: At the end of the follow-up, 67.1% patients showed no stage changes, 24.3% a stage improvement, and 8.6% a stage progression. Worsened patients showed higher rates of comorbid disorders and higher rates of unfavorable employment characteristics compared to the other subgroups (P < .05). Patients with worsened stage showed higher prevalence of somatic obsessions (P < .05), while patients with improved stage showed higher rates of magical thinking and violence/harm obsessions compared to other groups (P < .05)., Discussion: The present results provide epidemiologic and clinical correlates of the first application of a staging model in a sample of OCD patients, encouraging further studies to assess the utility of this approach in the field.

Background: Obsessive-compulsive disorder (OCD) is a prevalent and severe clinical condition. Robust evidence suggests a gene-environment interplay in its etiopathogenesis, yet the underlying molecular clues remain only partially understood. In order to further deepen our understanding of OCD, it is essential to ascertain how genes interact with environmental risk factors, a cross-talk that is thought to be mediated by epigenetic mechanisms. The human microbiota may be a key player, because bacterial metabolites can act as epigenetic modulators. We analyzed, in the blood and saliva of OCD subjects and healthy controls, the transcriptional regulation of the oxytocin receptor gene and, in saliva, also the different levels of major phyla. We also investigated the same molecular mechanisms in specific brain regions of socially isolated rats showing stereotyped behaviors reminiscent of OCD as well as short chain fatty acid levels in the feces of rats., Results: Higher levels of oxytocin receptor gene DNA methylation, inversely correlated with gene expression, were observed in the blood as well as saliva of OCD subjects when compared to controls. Moreover, Actinobacteria also resulted higher in OCD and directly correlated with oxytocin receptor gene epigenetic alterations. The same pattern of changes was present in the prefrontal cortex of socially-isolated rats, where also altered levels of fecal butyrate were observed at the beginning of the isolation procedure., Conclusions: This is the first demonstration of an interplay between microbiota modulation and epigenetic regulation of gene expression in OCD, opening new avenues for the understanding of disease trajectories and for the development of new therapeutic strategies., (© 2022. The Author(s).)