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Introduction Depression represents a significant challenge in terms of disability among the elderly population and its responsiveness to conventional treatment approaches tends to diminish in this population group. Esketamine has shown both effectiveness and safety in addressing treatment-resistant depression in older patients. Objectives Currently, there is a lack of available literature regarding the use of esketamine in the treatment of patients experiencing both cognitive decline and treatment-resistant depression (TRD). We administered esketamine to a 79-year- old patient to evaluate the effectiveness and tolerance of the medication. Methods We recruited a 79 year old female referred to the outpatient clinics of Pavia suffering from TRD with current Severe Depressive Episode (scoring 42 on the MADRS) with cognitive impairment (MMSE 16/30). The patient was on a fourth-line treatment. First-line treatment was started with paroxetine 40 mg from september 2021 to May 2022, switched to sertraline 50 mg. Second-line treatment with quetiapine 150 mg from June 2022 to December 2022 failed, despite optimal compliance for both lines of treatment. Then third line treatment with fluoxetine 20 mg, olanzapine 10 mg was initiated from December 2022 to May 2023. Study duration was 12 weeks. Anamnestic data and psychometric (MADRS, HAMD-21, HAM-A) and cognitive (MMSE and MoCA TEST) assessment were collected from medical records at baseline (T0), one month (T1) and three month (T2) follow-ups. Results MADRS, HAM-A and HAM-D values decreased significantly at T1 and T2 follow-ups. T0: MADRS 42, HAM-D 33, HAM-A 54; T1: MADRS 18, HAM-D 12, HAM-A 15; T2: MADRS 4, HAM-D 5, HAM-A 10. We also observed an improvement in cognitive test: T0: MMSE 16/30, MoCA test 4/30; T1: MMSE 18/30, MoCA test 6/30; T2: MMSE 20/30, MoCA test 8/30. The patient reported one episode of hypertension treated with clonidine after two moth of treatment, and mild prolonged motor slowing lasting about two hours after esketamine in the first month. Conclusions This case documented a successful treatment using intranasal esketamine in combination with an SSRI (Fluoxetine) for an older individual with cognitive impairment and a persistent anxiety-depressive syndrome. This approach was employed as a therapeutic intervention after multiple unsuccessful attempts with other antidepressant medications. Our findings confirmed the safety and tolerability of esketamine in an elderly female with cognitive impairment. Although a minor improvement in cognitive abilities has been noted, secondary dysfunction attributable to vascular-based cognitive decline remained. In terms of cognitive tolerance, derivatives of ketamine could potentially serve as an alternative to electroconvulsive therapy in cases of treatment-resistant depression, potentially improving short-term cognitive outcomes. Disclosure of Interest None Declared

Introduction Borderline personality disorder is often associated with comorbid conditions such as eating disorders, mood disorders, and substance use disorders. The prevalence of BPD and major depressive disorder (MDD) are about 5.9% and 8%, respectively, but up to 80% of patients with BPD experience one or more episodes of MDD in their lifetime. BPD is associated with suicidal behaviors and self-harm, thei are also fifty times more likely than the general population to attempt or die by suicide, Up to 10% of BPD patients will die by suicide Objectives Our aim is to verify if Esketamine could be effectiveness in treating patterns of behavior that have proven to be socially disruptive like self harm, suicidal attempts in patients with BPD. Suicidal ideation is a major risk factor for suicide in patients with TRD and BPD. The interval between the onset of suicidal ideation and suicide attempt is often very short, highlighting the need for urgent intervention and the development of new rapid-onset antidepressant therapies. Methods We recruited 25 adult subjects referred to the outpatient clinics of Pavia suffering from TRD with current Moderate-Severe Depressive Episode (scoring ≥ 22 on the MADRS). Of them 9/25 patients has a BPD. Study duration was 8 weeks.The following evaluation scales were administered before the first drug administration (T0) and repeated after one week (T1), four weeks (T2) and eight weeks (T3) of treatment: Montgomery Asberg Depression Rating Scale (MADRS), Columbia-Suicide Severity Rating Scale (CSSRS), and The Zanarini Rating Scale for BPD subgroup patients. We also collected sociodemographic and clinical information. Dosages and frequency of esketamine administration during the study period, adverse events and reasons for discontinuation were also recorded. Results A significant reduction of depressive symptoms was found at T1 and T2 compared to T0. Suicidal ideation disappeared as early as T1 and was maintained at T2, expecially in the BPD group. In the subgroup with borderline disorder we saw more improvement in impulsive (Self-mutilation and/or suicidal efforts; two other forms of impulsivity) and affective categories ( Inappropriate anger / frequent angry acts; chronic feelings of emptiness; mood instability) in Zanarini Rating Scale. Conclusions Our findings support the safety and tolerability of esketamine in TRD and BPD comorbidity sample. It is noteworthy that esketamine has an action on various pathways that are considered defective in borderline patients. Glutamate plays a key role in personality traits such as impulsivity, aggression, and suicidal behavior. Treatment with esketamine could reduce the number of suicide attempts and help reduce the self-harm of BPD. Disclosure of Interest None Declared

Introduction Treatment resistant schizophrenia still represents a major clinical and pharmacological challenge.30% of patients diagnosed with schizophrenia is characterised by a poor response to at least two different antipsychotics administered for a proper period of time and at adequate doses. Clozapine still represents the gold standard for treatment resistant patients. Unfortunately, a significant percentage of these are only partial responders. Augmentation strategies must be set up and atypical antipsychotic drugs are used in clinical practice. Promising findings have been observed in patients treated with Lurasidone as an add-on therapy with Clozapine. This novel second-generation antipsychotic has a unique receptor profile, showing 5-HT1a partial agonism and 5HT7 antagonism. These properties could also explain its procognitive effect, as several preclinical studies in literature have demonstrated. Objectives The aim of our study is to highlight the advantages of add on therapy with Lurasidone compared with treatment as usual (i.e. Clozapine + another atypical antipsychotic) in treatment resistant schizophrenia patients. Methods We conducted an observational study in a sample of 20 patients diagnosed with treatment resistant schizophrenia, based on DSM-5 diagnostic criteria and psychopharmacologic history. Treatment choices were taken independently by clinicians in charge of each patient. 10 subjects underwent Lurasidone augmentation of Clozapine, whereas the remaining 10 subjects were treated as usual with Clozapine and another atypical antipsychotic. PANSS and BPRS scales to assess general psychopathology and UKU side effects scale were administered both at baseline and at follow-up (T1= 1 month; T2=6 months). Results All patients treated with Lurasidone augmentation strategy achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported. In particular, Lurasidone showed no impact on metabolic parameters nor on ECG features, namely the QTc interval. The psychopathological improvement appeared higher in patients who received Lurasidone than in those treated as usual. This was particularly evident in cognitive domains. Conclusions Our observation suggests that augmentation strategy with Lurasidone to Clozapine can lead to clinically significant improvements in psychopathology when compared to Clozapine combined with another atypical antipsychotic, with a good tolerability profile. In future we will increase the number of our sample and the duration of follow-up time. In order to have more relevant statistical results, further research on this topic is needed. Disclosure of Interest None Declared

Introduction Brexpiprazole is a novel antipsychotic drug. It exerts antagonistic activity at the serotonin 5HT2A, 5HT2B, 5HT7 and noradrenaline alpha 1b/2c receptors; it also acts as partial agonist of serotonin 5HT1 and dopamine D2, D3 receptors. Brexpiprazole is approved for the treatment of schizophrenia and as an add-on therapy for major depression. Objectives This pilot study aims at exploring efficacy and tolerability of Brexpiprazole in a small sample of patients diagnosed with either a psychotic or a mood disorder. Methods This observational study was conducted at our Acute Psychiatric Inpatient Unit. We included 7 patients (5 males, 2 females) hospitalized between 2020 and 2021, diagnosed with schizophrenia spectrum disorders or mood disorders with psychotic symptoms confirmed by Mini International Neuropsychiatric Interview. Patients who participated signed an informed consent. Information concerning diagnosis, demographic characteristics (age, sex, education, marital status) and pharmacological therapy were collected examining clinical records. The average lenght of hospitalization was 13.4 days. Psychopathology was assessed by means of the PANSS and the severity of the illness was evaluated with CGI severity scale (CGI-S), both on admission and discharge. We also administered the UKU scale to evaluate the tolerability profile. Results . Results can be seen in figures 1, 2, 3 Conclusions Our study found a significant improvement in both positive and negative symptoms, with good tolerability. Limitations of our study are: small sample size and limited period of observation. These premises suggest that further research is needed in order to elucidate the exact mechanisms underlying Brexpiprazole’s action and the possible implication in mood disorders. Disclosure No significant relationships.

Abstract Background In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). Methods A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. Results A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper–hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. Conclusions Our study reports a strong correlation between autism spectrum and CS.

Introduction COVID-19 is an infectious disease caused by SARS-CoV-2. The WHO on March 11, 2020, has declared the novel coronavirus outbreak a global pandemic. Several studies found an association between the COVID-19 pandemic and psychiatric symptoms, such as distress, anxiety, fear of infection, depression and insomnia in the general population. Therefore, psychiatrists have been professionally overloaded, trying to manage the psychosocial impact of the pandemic and suffering its effects in person. Objectives To evaluate the disease perceptions, distress and burnout among psychiatrists from the Department of Mental Health and Addictions of Pavia in three different times, which correspond to the three main phases of the pandemic management in Italy: T0 is the first peak of the infections and the lock-down, from March to June; T1 is the reduction of the infections and the reopening, from June to October; T2 is the second wave of infections with a new progressive closure, the current one. Methods We used three questionnaires: the BIPQ (Brief Illness Perception Questionnaire), the PSS-10 (Perceived Stress Scale-10), the PED (Profile of emotional distress). We also used a survey (6 items) in T0, T1 and T2 to evaluate exposure, perception, quality of life and burnout. Results table 1,2,3. BIPQ: no one was exposed. Conclusions The increase of individual, who seeking help for mental health, impact on the perception of stress and on the emotional distress, even though psychiatrists have an adequate perception of COVID-19.

Introduction Some studies in literature highlight the correlation between immune-mediated inflammatory processes and psychiatric pathologies. However, there are few studies about the efficacy of IV immunoglobulins in psychiatric features (1). (1) ZUNSZAIN, Patricia A.; HEPGUL, Nilay; PARIANTE, Carmine M. Inflammation and depression. In: Behavioral neurobiology of depression and its treatment. Springer, Berlin, Heidelberg, 2012. p. 135-151. Objectives Case report: a 39 year patient diagnosed with borderline personality disorder and myasthenia was hospitalized for self-injury ideation, acting out and depressive episode treated with acid valproic, aripiprazole, gabapentin; flare-up of myasthenia that needed treatment. Methods Clinical and test evaluation was performed in three stages: before (t0), immediately after (t1) and 3 weeks after (t2) the administration of the IgEV without other treatment modifications. We have used: - Inventory of Statements About Self-Injury (ISAS) - Barrat Impulsiveness Scale, Version 11 (BIS-11) - Hamilton Anxiety Rating Scale (HAM-A) - Montgomery-Asberg Depression Rating Scale (MADRS) - Alexian Brothers Urge to Selfe-Injure Scale (ABUSI) Results The patient has a score of 79 at BIS-11. She used to have a huge number of acting aout as we see on ISAS (Fig.1). Figure 1 Figure 2 Conclusions We observed a reduction in non-suicidal self-injurious ideation, the suspension of acting-out, a complete remission of depressive symptoms with mild persistence of anxious symptoms immediately after the administration of immunoglobulins, and the remission continue until one month after the administration (Fig.2). Disclosure No significant relationships.

Introduction Individual abilities to perceive internal and external sensations are defined respectively as interoception and exteroception: the dysregulation of these functions can explain many psychotic symptoms. (Ardizzi et al. 2016) Objectives We evaluated the differences in the interoceptive and exteroceptive perception between 39 patients with psychosis and 250 healthy controls using self-administered questionnaires. The association between interoception and exteroception in the two groups was also tested. Methods The tests we used are AASP (Adolescent / Adult Sensory Profile) and MAIA (Multidimensional Assessment of Interoceptive Awareness). Differences were measured with t-tests, associations with spearman’s correlation. Results Significant differences emerged between the two samples in the AASP total score and in its Low registration (LR) and Sensory Avoiding (SA) sub-scales and in the MAIA total score and in all its sub-scales except “Not Worrying” (Fig.1). Different patterns of associations between AASP and MAIA were observed: psychotic patients showed negative correlations between MAIA and AASP in the LR and Sensation Seeking (SS) sub-scales and in the auditory (AU) and tactile (TO) sensory channels. Healthy controls, positive correlations emerged between MAIA and AASP in the Sensation Seeking (SK) sub-scale and in the “perception of movement” (MO) sub-score (Fig.2)(Fig.3). Conclusions Higher scores of psychotic patients in AASP and MAIA reveal both a disregulated sensory related behavior and a hightened awareness towards internal stimuli. The negative correlation between the two scales in psychotic subjects highlights the importance of the interaction between internal and external perception in determining the global subjective experience.

There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in eTable 12., (Copyright © 2024. Published by Elsevier B.V.)

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ 2 , penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies., Competing Interests: Declaration of competing interest Conflict of interest statements of all authors are detailed in eTable 8., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide., Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization-Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori- defined individual/cumulative risk factors were measured. A χ 2 , penalized cubic splines, linear regression, and correlation analyses were conducted., Results: Analyzing 8,115 of 8,762 initiated surveys (representative = 75.1%), the pre-pandemic WHO-5 and P-score remained stable during the study (excluding relevant recall bias/drift), but worsened during the pandemic by 5.55 ± 17.13 (SD) and 6.74 ± 16.06 points, respectively (effect size d = 0.27 and d = 0.28). The proportion of adolescents with WHO-5 scores suggesting depression screening (<50) and major depression (<29) increased from 9% to 17% and 2% to 6%. WHO-5 worsened (descending magnitude, with cumulative effect) in adolescents with a mental or physical disorder, female gender, and with school closure. Results were similar for the P-score, with the exception of school closure (not significant) and living in a low-income country, as well as not living in a large city (significant). Changes were significantly but minimally related to COVID-19 deaths/restrictions, returning to near-pre-pandemic values after >2 years. The 3 most subjectively effective coping strategies were Internet use, exercise/walking, and social contacts., Conclusion: Overall, well-being/mental health worsened (small effect sizes) during the early stages of the COVID-19 pandemic, especially in vulnerable subpopulations. Identified at-risk groups, association with pandemic-related measures, and coping strategies can inform individual behaviors and global public health strategies., Study Preregistration Information: Physical and mental health impact of COVID-19 on children, adolescents, and their families: The Collaborative Outcomes study on Health and Functioning during Infection Times - Children and Adolescents (COH-FIT-C&A); https://doi.org/10.1016/j.jad.2021.09.090 DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. We actively worked to promote sex and gender balance in our author group. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The scientific literature shows some gender differences in the clinical course of schizophrenia. The aim of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by schizophrenia. This would allow for the implementation of individualized treatment strategies., Methods: We examined a large set of clinical and biochemical parameters. Data were obtained from clinical charts and blood analyses from a sample of 555 schizophrenia patients consecutively admitted for exacerbation of symptoms to the inpatient clinic of Fondazione IRCCS Policlinico (Milan) or ASST Monza in Italy from 2008 to 2021. Univariate analyses, binary logistic regression, and a final logistic regression model were performed with gender as dependent variable., Results: The final logistic regression models showed that male patients (compared to females) were more prone to lifetime substance use disorders (p = 0.010). However, they also had higher GAF (global functioning) mean scores (p < 0.001) at the time of hospitalization. Univariate analyses showed that male patients (with respect to females) had an earlier age at onset (p < 0.001), a more frequent family history of multiple psychiatric disorders (p = 0.045), were more often smokers (p < 0.001), had a more frequent comorbidity with at least one psychiatric disorder (p = 0.001), and less often suffered from hypothyroidism (p = 0.011). In addition, men had higher levels of albumin (p < 0.001) and bilirubin (t = 2.139, p = 0.033), but lower levels of total cholesterol (t = 3.755, p < 0.001)., Conclusions: Our analyses indicate a less severe clinical profile in female patients. This is evident especially in the early years of the disorder, as suggested by less comorbidity with psychiatric disorders or later age at onset; this is consistent with the related literature. In contrast, female patients seem to be more vulnerable to metabolic alterations as demonstrated by more frequent hypercholesterolemia and thyroid dysfunction. Further studies are needed to confirm these results in the framework of precision medicine., (© 2023. The Author(s).)

Background: A significant number of young individuals are readmitted one or more times shortly after their first episode of psychosis. Readmission may represent a marker of psychopathological vulnerability. Our primary aim was to evaluate the impact of clinical and socio-demographic variables on readmission at 12-month follow-up. Secondly, our goal was to determine whether the use of Long-Acting Injection (LAI) antipsychotics provides notable benefits compared to oral medications in preventing subsequent readmissions., Subjects and Methods: 80 patients hospitalised for the first time with a diagnosis of psychotic disorder (ICD-10 criteria) were retrospectively assessed through clinical records. The mean age was 21.7 years. Patients were predominantly male (n = 62, 77.5%), and 55 subjects had at least 8 years of education. 50% of the sample was "NEET" (not in education, employment, or training)., Results: 35 patients (43.8%) were discharged with a LAI antipsychotic, while 45 (56.2%) recieved oral antipsychotic therapy. Substance use ( p = 0.04) and oral antipsychotics at discharge ( p = 0.003) were significantly associated with readmission at 1 year. We did not find any significant predictors of being discharged with LAI therapy., Conclusion: Our findings underlined the importance of identifying patients at risk of readmission in order to prevent future rehospitalization and promote appropriate prevention strategies. LAIs should be considered as a first-choice treatment for patients hospitalised for FEP since they proved to be effective in preventing relapse.

We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life., (© 2024 World Psychiatric Association.)

Introduction: The natural history of autoimmune gastritis (AIG) has been poorly described. In this study, we report the long-term natural history and clinical clustering of the full spectrum of AIG, from the potential to the complicated stage., Methods: Prospective single-center study conducted in a tertiary referral center. Patients with AIG at any stage (0 = potential; 1 = early; 2 = florid; 3 = severe; and 4 = complicated) were enrolled (January 2000-December 2022). The histopathological evolution, the clinical presentation, and the correlates of evolution of potential AIG were assessed., Results: Four hundred ninety-eight patients with AIG (mean age 56.7 ± 15.2 years, F:M ratio 2.5:1) were included, of whom 93 experienced potential AIG. The maximum disease duration was 27 years (median 18, interquartile range 14-23), while the overall median follow-up was 52 months (interquartile range 12-95). Age was significantly lower in stage 0 compared with that in the other stages. Accidental histologic evidence and hematologic findings were the most common clusters of diagnosis. The overall median rate of progression was 7.29 per 100 persons/yr (95% confidence interval [CI] 6.19-8.59), while the stage-specific rates of progression were 10.85 (stage 0; 95% CI 7.75-15.18), 14.83 (stages 1-2; 95% CI 11.89-18.49), and 2.68 (stage 3; 95% CI 1.88-3.84). Newly onset neoplastic complications at follow-up occurred in 41/483 patients (8.5%; 23 neuroendocrine tumors and 18 epithelial dysplasia). No cases of adenocarcinoma were noticed. Male sex was associated with a greater likelihood of evolving from potential AIG to overt AIG., Discussion: AIG is a progressive disorder, with a virtually absent risk of gastric adenocarcinoma. Patients with potential AIG should be monitored because they carry a high risk of evolving into overt AIG., (Copyright © 2024 by The American College of Gastroenterology.)

Introduction: Treatment-resistant depression (TRD) is commonly defined as the failure of at least two trials with antidepressant drugs, given at the right dose and for an appropriate duration. TRD is associated with increased mortality, compared to patients with a simple major depressive episode. This increased rate was mainly attributed to death from external causes, including suicide and accidents. The aim of our study is to identify socio-demographic and psychopathological variables associated with suicidal attempts in a sample of outpatients with TRD., Material and Methods: We performed a monocentric observational study with a retrospective design including a sample of 63 subjects with TRD referred to an Italian outpatient mental health centre. We collected socio-demographic and psychopathological data from interviews and clinical records., Results: 77.8% of the sample (N=49) were females, the mean age was 49.2 (15.9). 33.3% (N=21) of patients had attempted suicide. 54% (N=34) of patients had a psychiatric comorbidity. Among the collected variables, substance use (p=0.031), psychiatric comorbidities (p=0.049) and high scores of HAM-D (p=0.011) were associated with the occurrence of suicide attempts. In the regression model, substance use (OR 6.779), psychiatric comorbidities (OR 3.788) and HAM-D scores (OR 1.057) were predictive of suicide attempts. When controlling for gender, only substance use (OR 6.114) and HAM-D scores (OR 1.057) maintained association with suicide attempts., Conclusion: The integrated treatment of comorbidities and substance abuse, which involves different mental health services, is fundamental in achieving the recovery of these patients. Our study supports the importance of performing a careful clinical evaluation of patients with TRD in order to identify factors associated with increased risk of suicide attempts., 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 © 2024 Civardi, Besana, Carnevale Miacca, Mazzoni, Arienti, Politi, Brondino and Olivola.)

Background: The clinical high risk for psychosis (CHR-P) construct represents an opportunity for prevention and early intervention in young adults, but the relationship between risk for psychosis and physical health in these patients remains unclear., Methods: We conducted a RECORD-compliant clinical register-based cohort study, selecting the long-term cumulative risk of developing a persistent psychotic disorder as the primary outcome. We investigated associations between primary outcome and physical health data with Electronic Health Records at the South London and Maudsley (SLaM) NHS Trust, UK (January 2013-October 2020). We performed survival analyses using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models., Results: The database included 137 CHR-P subjects; 21 CHR-P developed psychosis during follow-up, and the cumulative incidence of psychosis risk was 4.9% at 1 year and 56.3% at 7 years. Log-rank tests suggested that psychosis risk might change between different levels of nicotine and alcohol dependence. Kaplan-Meier curve analyses indicated that non-hazardous drinkers may have a lower psychosis risk than non-drinkers. In the Cox proportional hazard model, nicotine dependence presented a hazard ratio of 1.34 (95% CI: 1.1-1.64) ( p = 0.01), indicating a 34% increase in psychosis risk for every additional point on the Fagerström Test for Nicotine Dependence., Conclusions: Our findings suggest that a comprehensive assessment of tobacco and alcohol use, diet, and physical activity in CHR-P subjects is key to understanding how physical health contributes to psychosis risk.

Understanding the cognitive processes that contribute to mental pain in individuals with psychotic disorders is important for refining therapeutic strategies and improving patient outcomes. This study investigated the potential relationship between mental pain, mind wandering, and self-reflection and insight in individuals diagnosed with psychotic disorders. We included individuals diagnosed with a 'schizophrenia spectrum disorder' according to DSM-5 criteria. Patients in the study were between 18 and 65 years old, clinically stable, and able to provide informed consent. A total of 34 participants, comprising 25 males and 9 females with an average age of 41.5 years (SD 11.5) were evaluated. The Psychache Scale (PAS), the Mind Wandering Deliberate and Spontaneous Scale (MWDS), and the Self-Reflection and Insight Scale (SRIS) were administered. Statistical analyses involved Spearman's rho correlations, controlled for potential confounders with partial correlations, and mediation and moderation analyses to understand the indirect effects of MWDS and SRIS on PAS and their potential interplay. Key findings revealed direct correlations between PAS and MWDS and inverse correlations between PAS and SRIS. The mediation effects on the relationship between the predictors and PAS ranged from 9.22% to 49.8%. The largest statistically significant mediation effect was observed with the SRIS-I subscale, suggesting that the self-reflection and insight component may play a role in the impact of mind wandering on mental pain. No evidence was found to suggest that any of the variables could function as relationship moderators for PAS. The results underscore the likely benefits of interventions aimed at reducing mind wandering and enhancing self-reflection in psychotic patients (e.g., metacognitive therapy, mindfulness). Further research will be essential to elucidate the underlying mechanisms.

Background: In the recent years, several studies have shown a correlation between autism spectrum disorder (ASD) and catatonia. It is also known that both conditions are found to be associated with mood disorders. This study aimed to investigate the relationship between autistic traits and catatonic symptoms, as well as the potential mediating role of mood disorder spectrum in the relationship between them., Methods: The total sample of 514 subjects was composed by four diagnostic groups, composed by patients affected by catatonia (CTN), borderline personality disorder (BPD), major depressive disorder (MDD) and healthy controls (HC). Subjects were assessed with the SCID-5-RV, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Catatonia Spectrum (CS) and the Mood Spectrum Self-Report (MOODS-SR). Statistical analyses included Pearson's coefficient calculation, multiple linear regression, and mediation analysis., Results: all the correlations appear to be strongly positive and significant with the strongest coefficient emerging between AdAS Spectrum total score and CS total score ( r  = 0.762, p  < 0.001). The Mediation Analysis showed that AdAS Spectrum total score showed a significant indirect effect on CS total score through MOODS-SR total score ( b  = 0.168, 95% bootstrapped CI [0.127:0.207])., Conclusion: The present study highlights the presence of a mediating role of the mood disorder spectrum in the relationship between autistic traits and the catatonia spectrum., 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 Dell’Osso, Amatori, Carpita, Massimetti, Nardi, Gravina, Benedetti, Bonelli, Casagrande, Luciano, Berardelli, Brondino, De Gregorio, Deste, Nola, Reitano, Muscatello, Pompili, Politi, Vita and Maj.)

Background: Although it has been proposed that childhood adversities (CAs) may affect the hypothalamic-pituitary-adrenal (HPA) axis activity and psychotic symptoms severity, these associations have not been fully confirmed in first-episode psychosis (FEP). This study explored the association between CA, cortisol and psychotic symptoms in FEP patients., Methods: 81 FEP patients were enrolled. CAs were evaluated by the Childhood Experience of Care and Abuse Questionnaire and a semi-structured interview. Psychotic symptoms were evaluated by the Positive and Negative Syndrome Scale. Cortisol level was collected using saliva samples. ANCOVA and partial correlation analyses were run., Results: FEP patients with childhood abuse reported severe positive symptoms than those without CA. FEP patients with at least one CA had higher levels of cortisol awaking, cortisol at 12 a.m., and cortisol at 8 p.m. Morning cortisol levels were negatively correlated with the severity of negative symptoms and positively correlated with the severity of general psychopathology. Evening cortisol levels were positively correlated with severity of general psychopathology., Conclusion: FEP patients with CAs, compared with those without CA, might report more severe positive symptoms and higher cortisol, even though these findings as prone to bias due to the small sample size, and should be seen in the larger perspective of conflicting evidence in the field.

Background: Recent literature has highlighted that catatonia may be more prevalent among psychiatric patients than previously thought, beginning from autism spectrum disorders (ASD), for which it has been suggested to represent a severe late consequence, but also among individuals with mood disorders and borderline personality disorder (BPD). Interestingly, one critical point shared by these conditions is the increased risk of suicidality. The aim of this study was to evaluate how the presence and the prevalence of catatonic symptoms may shape and correlate with suicidal risk in a sample of individuals with major depressive disorder (MDD) or BPD., Methods: We recruited two clinical samples of subjects (BPD and MDD) and a control group without a diagnosis according to DSM-5 (CTL). Subjects were assessed with the catatonia spectrum (CS) and the MOODS-SR for evaluating suicidality., Results: In the total sample, suicidality score was significantly and positively correlated with all CS domains and CS total score. Correlation and regression analyses highlighted specific patterns of association among Catatonia spectrum domains and suicidality in the MDD and BPD group and in the total sample., Conclusion: In both disorders, higher catatonic traits are linked to higher suicidal tendencies, confirming the high risk of suicide for this population. However, different patterns of association between catatonic symptoms and suicidality were highlighted in the two disorders., 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 Dell’Osso, Nardi, Bonelli, Gravina, Benedetti, Amatori, Battaglini, Massimetti, Luciano, Berardelli, Brondino, De Gregorio, Deste, Nola, Reitano, Muscatello, Pompili, Politi, Vita, Carmassi, Cremone, Carpita and Maj.)

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group., Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings., Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum., Competing Interests: Declaration of Competing Interest Celso Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Julio Bobes has received research grants and served as a consultant, advisor, or speaker within the last 5 years for AB-Biotics, Acadia Pharmaceuticals, Alkermes, Allergan, Ambrosetti-Angelini, Biogen, Casen Recordati, D&A Pharma, Exeltis, Gilead, Indivior, GW Pharmaceuticals, Janssen-Cilag, Jazz Pharmaceuticals, Lundbeck, Mundipharma, Newron, Otsuka, Pfizer, Roche, Sage Therapeutics, Servier, Schwabe Farma Ibérica, Shire, and Takeda and has received research funding from the Spanish Ministry of Economy and Competiveness –Centro de Investigación Biomedica en Red area de Salud Mental (CIBERSAM) and Instituto de Salud Carlos III– and the Spanish Ministry of Health. Maria Paz García-Portilla has been a consultant to and/or has received honoraria/grants from Angelini, Otsuka-Lundbeck Alliance, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, and Sage Therapeutics. Pilar A. Sáiz has been a consultant to and/or has received honoraria/research grants from Adamed, Alter Medica, Angelini Pharma, CIBERSAM, Ethypharm Digital Therapy, European Commission, Government of the Principality of Asturias, Instituto de Salud Carlos III, Janssen-Cilag, Lundbeck, Otsuka, Pfizer, Plan Nacional Sobre Drogas, and Servier. Miguel Bernardo has been a consultant for, received grant/research support and honoraria from, and been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda., (Copyright © 2023. Published by Elsevier B.V.)

Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score"., Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed., Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex., Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in Supplementary Table 7., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: We aimed at evaluating hepatitis C virus (HCV) prevalence and treatment referral outcomes in a large population of drug users in Northern Italy., Material and Methods: Each participant underwent a quick capillary blood test. Positive participants underwent HCV RNA quantification. HCV RNA positive subjects were referred to treatment and evaluated immediately at the end of treatment and at 3 and 6 months after treatment., Results: Of the 636 participants tested, 244 were positive. Intravenous drug use was more frequent among subjects who tested positive for HCV antibodies (99%). Among subjects who tested positive, 68% were HCV-RNA positive while 32% were negative. Among people referred to treatment, nearly 30% did not show up while 70% completed the treatment with success. Over 99% of people who started direct-acting antiviral agent (DAA) have a sustained response., Discussion: We observed a significant higher prevalence of HCV positive subjects among people who inject drugs (99%) and we observed a high success rate for HCV treatment engagement., Conclusions: Rapid testing for HCV represents a potential tool for HCV screening among high-risk groups.

Purpose: Clozapine represents the criterion standard therapy for patients with treatment-resistant schizophrenia. Unfortunately, a significant percentage of such patients are also partial responders to clozapine. Consequently, several augmentation strategies have been proposed with various and sometimes controversial efficacy. Among these add-on treatments, lurasidone has been recently introduced and could represent a potential option, especially for the additional positive effect on cognitive symptoms., Methods: This case series aims to determine possible advantages of lurasidone augmentation in four patients treated with clozapine, who were diagnosed with treatment-resistant schizophrenia. Positive and Negative Syndrome Scales were used to evaluate psychopathology, the Udvalg for Kliniske Undersøgelser scale for tolerability and safety., Finding: All patients achieved a significant reduction of both positive and negative symptoms, with no significant adverse effects to be reported., Implications: Our observation suggests that lurasidone can lead to clinically significant improvements in psychopathology with a good tolerability profile when added to clozapine., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Electrodermal Activity (EDA) has become of great interest in the last several decades, due to the advent of new devices that allow for recording a lot of psychophysiological data for remotely monitoring patients' health. In this work, a novel method of analyzing EDA signals is proposed with the ultimate goal of helping caregivers assess the emotional states of autistic people, such as stress and frustration, which could cause aggression onset. Since many autistic people are non-verbal or suffer from alexithymia, the development of a method able to detect and measure these arousal states could be useful to aid with predicting imminent aggression. Therefore, the main objective of this paper is to classify their emotional states to prevent these crises with proper actions. Several studies were conducted to classify EDA signals, usually employing learning methods, where data augmentation was often performed to countervail the lack of extensive datasets. Differently, in this work, we use a model to generate synthetic data that are employed to train a deep neural network for EDA signal classification. This method is automatic and does not require a separate step for features extraction, as in EDA classification solutions based on machine learning. The network is first trained with synthetic data and then tested on another set of synthetic data, as well as on experimental sequences. In the first case, an accuracy of 96% is reached, which becomes 84% in the second case, thus demonstrating the feasibility of the proposed approach and its high performance.

Background: The clinical high risk for psychosis (CHR-P) phase represents an opportunity for prevention and early intervention in young adults, which also could focus on improving physical health trajectories., Methods: We conducted a RECORD-compliant clinical register-based cohort study. The primary outcome was to describe the physical health of assessed CHR-P individuals, obtained via Electronic Health Records at the South London and Maudsley (SLaM) NHS Foundation Trust, UK (January 2013-October 2020)., Results: The final database included 194 CHR-P subjects (46% female). Mean age was 23.70 ± 5.12 years. Percentage of tobacco smokers was 41% (significantly higher than in the age-matched general population [24%]). We found that 49% of subjects who consumed alcohol had an AUDIT-C (Alcohol Use Disorder Identification Test) score above 5 (hazardous drinking), with an average score of 4.94 (significantly higher than in the general population [2.75]). Investigating diet revealed low fiber intake in most subjects and high saturated fat intake in 10% of the individuals. We found that 47% of CHR-P subjects met the UK recommended physical activity guidelines (significantly lower than in the general population [66%]). Physical parameters (e.g., weight, heart rate, blood pressure) were not significantly different from the general population., Conclusions: This evidence corroborates the need for monitoring physical health parameters in CHR-P subjects, to implement tailored interventions that target daily habits.

Background: Epigenetics of Autism Spectrum Disorders (ASD) is still an understudied field. The majority of the studies on the topic used an approach based on mere classification of cases and controls., Objective: The present study aimed at providing a multi-level approach in which different types of epigenetic analysis (epigenetic drift, age acceleration) are combined., Methods: We used publicly available datasets from blood (n = 3) and brain tissues (n = 3), separately. Firstly, we evaluated for each dataset and meta-analyzed the differential methylation profile between cases and controls. Secondly, we analyzed age acceleration, epigenetic drift and rare epigenetic variations., Results: We observed a significant epi-signature of ASD in blood but not in brain specimens. We did not observe significant age acceleration in ASD, while epigenetic drift was significantly higher compared to controls. We reported the presence of significant rare epigenetic variations in 41 genes, 35 of which were never associated with ASD. Almost all genes were involved in pathways linked to ASD etiopathogenesis (i.e., neuronal development, mitochondrial metabolism, lipid biosynthesis and antigen presentation)., Conclusion: Our data support the hypothesis of the use of blood epi-signature as a potential tool for diagnosis and prognosis of ASD. The presence of an enhanced epigenetic drift, especially in brain, which is linked to cellular replication, may suggest that alteration in epigenetics may occur at a very early developmental stage (i.e., fetal) when neuronal replication is still high., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

During the CoViD-19 pandemic, University students may have suffered from increased anxiety due to interferences in their relationships and in academic requirements, as didactic activities have moved to distance learning systems. However, being surrounded by supportive relationships and being motivated to cultivate personal interests might have decreased anxiety. In this pilot study, we collected the responses of 174 students from Italian University merit colleges to an online questionnaire, investigating their perceived anxiety, the quality of surrounding relationships, whether they were cultivating any personal interests and whether they had spent the period of lockdown in college or at home. Regression analyses indicated that both quality of relationships and personal interests predicted low levels of anxiety ( p  < 0.001). However, simple slope analyses showed that personal interests were negatively related to anxiety only at medium and high quality of relationships ( p  < 0.001), while no association was found at low quality of relationships. No differences were found between students who stayed in college or at home. These results suggest that Universities should promote accessibility to relationships and cultivation of personal interests to protect students' mental health during mass emergencies such as the current pandemic, in the perspective of improving community resilience., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2021.)

Cognitive deficits are associated with schizophrenia and show a progressive worsening, often being unresponsive to treatment. New antipsychotic molecules acting as antagonist at the serotoninergic 5-hydroxytryptamine receptor 7 (e.g. lurasidone) or partial agonists at dopamine D3 receptor (e.g. cariprazine) could have an impact on cognition in this patient group. The aim of the systematic review is to explore the efficacy of lurasidone and cariprazine in improving cognition in both animal models and human studies. The following terms: (lurasidone AND cognit*) OR (cariprazine AND cognit*) were searched in Web of Science from inception to December 2021. We included all studies that assessed changes in cognitive function after treatment with cariprazine or lurasidone. Of 201 selected articles, 36 were included. Twenty-four articles used animal models (rats, mice and marmosets), five evaluating the effects of cariprazine and 19 the effects of lurasidone. Twelve articles were clinical studies (cariprazine n = 2; lurasidone n = 10). In both animal and human studies lurasidone showed a greater efficacy on cognitive performance compared to placebo, quetiapine, ziprasidone or treatmentas- usual. Cariprazine was superior to other antipsychotics in improving cognitive functions in both animal and human studies. The cognitive effect of lurasidone could be explained by its potent antagonism at the 5-HT7 receptors combined with partial agonism at 5-HT1A receptors. The pro-cognitive effect of cariprazine is probably explained by its very high affinity for D3 receptors. Head-to-head studies comparing lurasidone and cariprazine are needed to establish the "first-choice" treatment for cognitive dysfunction associated with schizophrenia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

22q11.2 deletion syndrome (22q.11.2DS) might be one of the strongest genetic risk factors for psychosis, but robust estimates of prevalence and incidence of psychotic disorders in this condition are not available. To address this gap, we performed a multistep systematic PRISMA/MOOSE-compliant literature search of articles reporting prevalence (primary outcome) or incidence (secondary outcome) of psychotic disorders in 22q11.2DS samples (protocol: https://osf.io/w6hpg) using random-effects meta-analysis, subgroup analyses and meta-regressions. The pooled prevalence of psychotic disorders was 11.50% (95%CI:9.40-14.00%), largely schizophrenia (9.70%, 95%CI:6.50-14.20). Prevalence was significantly higher in samples with a mean age over 18 years, with both psychiatric and non-psychiatric comorbidities and recruited from healthcare services (compared to the community). Mean age was also significantly positively associated with prevalence in meta-regressions ( p  < 0.01). The pooled incidence of psychotic disorders was 10.60% (95%CI:6.60%-16.70%) at a mean follow-up time of 59.27 ± 40.55 months; meta-regressions were not significant. To our knowledge, this is the first comprehensive systematic review and meta-analysis of the prevalence and incidence of psychotic disorders in 22q11.2DS individuals. It demonstrates that around one in ten individuals with 22q11.2DS displays comorbid psychotic disorders, and around one in ten will develop psychosis in the following five years, indicating that preventive approaches should be implemented systematically in 22q11.2DS.

Background: Dairy products are frequently considered responsible for post-prandial symptoms and are withdrawn from the diet, even against medical advice. We analysed the symptoms patients consider as lactose related; we also evaluated if psychological profile may affect the interpretation of the relationship between lactose and symptoms. Methods: In 268 patients undergoing lactose breath test, symptoms considered evoked by lactose intake were recorded and their severity measured. In the second part, symptom onset of 40 randomly selected patients was detected after both lactose and glucose breath test were blindly performed. Questionnaires evaluating anxiety, suggestibility and personality trait were administered. Key Results : Symptoms depending on functional gastrointestinal disorders or reflux disease were frequent in self-reported lactose-intolerant patients. In comparison with lactose malabsorption, these symptoms proved to be more frequent in patients with negative lactose breath test. The blinded administration of lactose and glucose demonstrated that a correct link between lactose intake and symptom onset was possible, only in 47.5% of the subjects, making this test inaccurate. None of the investigated psychological characteristics were different between patients with a nocebo response and patients not experiencing nocebo. Conclusions : Patients with self-reported lactose intolerance are frequently unaware about clinical presentation of this condition, and correct information is needed. The detection of symptom onset after lactose is an inaccurate test for lactose intolerance. Furthermore, the analysis of psychological characteristics of patients undergoing hydrogen breath test is not useful to select the subgroup at risk for a nocebo response. New strategies to diagnose lactose intolerance are mandatory., Competing Interests: The authors declare no conflict of interest.

Objective: To report the personalized decision-making pro- cess adopted for a cochlear implant (CI) candidate requiring magnetic resonance imaging (MRI) brain surveillance., Study Design: Clinical capsule report., Setting: Tertiary academic referral center., Patient: A 23-year-old man affected by posttraumatic bilat- eral profound hearing loss, already in radiological follow-up for a suspected small left cuneal low-grade glioma., Interventions: A multidisciplinary approach involving preoperative MRI simulations and 3D printed (3DP) models aiming to adapt the CI position to facilitate MRI brain lesion visibility., Main Outcome Measures: MRI visibility and surgical approach., Results: Preoperative MRI scans with the placement of an Ultra 3D CI were performed simulating different implant location to assess the brain lesion visibility in MRI. CI was positioned 9 cm away from the external auditory canal with an angle of 90 degrees. To assess the technical feasibility of the surgical procedure, a patient-specific 3DP head model was produced preoperatively. The postoperative course was uneventful, the patient showed a significant benefit from CI, and the brain lesion was highly visible at the MRI follow-up., Conclusions: The employment of strategies aimed at improving the MRI quality in CI recipients still represents a topic requiring attention. Thanks to multidisciplinary team collaboration, in our case, the CI position was successfully determined to allow unhindered MRI visibility of a specific intracranial structure., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Aim: A growing body of literature has demonstrated the utility of a dimensional perspective on mental disorders. The current study aims to determine the psychometric properties of the Catatonia Spectrum (CS), a new questionnaire specifically tailored to assess the spectrum of catatonia, from full blown forms to subthreshold ones., Methods: 86 adults with at least three symptom criteria for catatonia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), 81 adults affected by borderline personality disorder (BPD), 104 adults with a diagnosis of major depressive disorder (MDD), and 105 subjects without mental disorders (CTL), were recruited from six Italian University Departments of Psychiatry and administered the: Bush-Francis Catatonia Rating Scale (BFCRS), Bush-Francis Catatonia Screening Instrument (BFCSI), and CS., Results: CS scale demonstrated a high level of internal consistency and excellent test-retest reliability for total and domain scores. CS domain scores were positively and significantly correlated with each other ( p < 0.001) with Pearson's coefficients ranging from 0.337 to 0.663. All the CS domain scores were highly correlated with the CS total score. The correlation coefficients between CS and alternative measures of catatonia appeared all significant and positive. Significant differences among diagnostic groups on both CS domains and total scores were found. CS total scores increased significantly and progressively from the CTL, to the MDD and the BDP group, up to the catatonia group, which reported the highest value., Conclusion: The CS showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of catatonia. The questionnaire performed differently across the four diagnostic groups, with an increasing score gradient from healthy controls to patients with MDD, BPD and up to the catatonia group., 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 © 2022 Dell’Osso, Amatori, Cappelli, Cremone, Massimetti, Gravina, Nardi, Benedetti, Chiarantini, Luciano, Berardelli, Brondino, De Gregorio, Deste, Nola, Reitano, Muscatello, Pompili, Politi, Vita, Carmassi and Maj.)

Autism spectrum disorder (ASD) is a group of life-long neurodevelopmental disorders affecting 1.5% of the general population. The present study aimed to evaluate the psychiatric history of a group of adults who received the first diagnosis of ASD in two Italian university centers. Diagnoses of ASD were confirmed by a team of psychiatrists with wide expertise in the field, after the administration of standardized tools (i.e., ADOS-2, ADI-R). The sample comprised 161 participants, of which 114 (79.5%) were males. The median age of diagnosis was 23 years (range 18-55), with a median IQ of 100 (range 30-145). The first evaluation by a mental health professional was performed at a median age of 13 years, with a gap of 11 years between the first evaluation and the diagnosis of ASD. 33.5% of participants had never received a psychiatric diagnosis, while the rest of the sample had received one or more diagnoses different from ASD. The most common past diagnoses were intellectual disability, psychoses, personality disorders, and depression. Sex differences were detected in the age of diagnosis and ADOS-2 scores. Our results provide important information for both child and adult psychiatrists. Given the prevalence of autism and the high rates of co-occurrent psychiatric conditions, it is important for clinicians to consider ASD in the differential diagnostic process., (© 2020. The Author(s).)

Major depression is a common comorbidity in autism spectrum disorder (ASD), often difficult to identify and to treat. Autistic subjects are more at risk for suicidal thoughts and behaviors compared to typically developing peers. Unfortunately, ASD individuals are more frequently treatment-resistant and often show side-effects which reduce efficacy. Intranasal esketamine has been recently approved as an add-on medication for treatment-resistant depression (TRD), but it has never been used in ASD with comorbid major depression. Of note, a pilot study of intranasal ketamine has shown no effect on social withdrawal in ASD without depression. The present case report describes the first girl with ASD and comorbid TRD treated with intranasal esketamine., (Copyright © 2022 Olivola et al.)

Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial., Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life., Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries., Limitations: Cross-sectional and anonymous design., Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed., Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others., Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive., Limitations: . Cross-sectional survey, preponderance of non-representative participants., Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics., (Copyright © 2021. Published by Elsevier B.V.)

Rationale: The use of intravenous valproate is not approved for clinical practice in psychiatry. Literature data pointed out for a potential usefulness of this route of administration for valproate, but there is no actual consensus., Objectives: The aim of the present systematic review is to assess the effectiveness of intravenous valproate in agitation as well as general safety., Methods: A systematic review of studies evaluating the use of intravenous valproate in agitation was conducted. Additionally, safety was evaluated in all randomized trials involving the use of intravenous valproate in all medical conditions (epilepsy, migraine and psychiatric conditions)., Results: For the systematic review on effectiveness in agitation, the search yielded 965 articles overall. After removing duplicates, 9411 articles were screened by title and abstract, and 39 of these were evaluated at a full-text level. Six studies were considered eligible for qualitative synthesis: one RCT and case report (n = 3), followed by cohort studies (n = 2). For the systematic review on safety, twenty-two RCTs were considered eligible for quantitative synthesis., Conclusion: Intravenous valproate seems efficacious in reducing agitation in psychiatric patients; it generally appears safe compared to other neuroleptics or antiepileptics. However, the evidence is still not strong as it  relies mainly on open-label studies or case series., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Ehlers-Danlos syndromes (EDS) have been associated with psychological distress, comorbid psychiatric disorders, and worsening in quality of life (QoL). Among the neurodevelopmental disorders, autism spectrum disorders (ASD) have shown the highest rates of co-occurrence with EDS. The reasons for these associations are unknown and a possible role of pain in increasing the risk of psychiatric disorders in EDS has been suggested. However, a detailed picture of an Italian EDS sample is still lacking., Methods: We conducted a web-based survey in a third level center for the diagnosis of EDS in northern Italy, to investigate psychological distress, QoL, and the presence of autistic traits. Furthermore, we correlated the psychometric data with some clinical variables., Results: We observed a high rate of psychological distress with 91% of the responders at high risk of common mental disorders, low QoL, and high prevalence of autistic traits in EDS patients. Specifically, patients lacking a specific genetic test, diagnosed as suspects of EDS appeared to be at greater risk and reported worse psychological QoL. Pain was significantly associated with both psychological distress and worse QoL., Conclusions: Our findings support the need of further research and of a multi-disciplinary approach to EDS including psychological and psychiatric liaison.

Background: Autoimmune atrophic gastritis (AAG) leads to vitamin B12 deficiency that may manifest with neuropsychiatric disorders, such as emotional instability, cognitive deficits, depression, and personality changes., Aims: To evaluate the quality of life (QoL) in patients with AAG and the interplay between QoL, psychopathological symptoms, and demographic factors., Methods: This is an observational, cross-sectional study including 102 patients with AAG (mean age 62 ± 13 years), 100 with functional gastrointestinal disorders (mean age 38.3 ± 17 years), 100 with other chronic organic gastrointestinal diseases (mean age 50.9 ± 21.4 years), and 100 healthy controls (mean age 37.5 ± 18.9 years). The 36-Item Short Form Health Survey questionnaire (SF-36) and the General Health Questionnaire-12 were administered. The results of the scales were compared among the study groups. Linear regression analyses were fitted to identify independent predictors of QoL in AAG patients., Results: QoL was significantly different among the four groups in all subdomains. In particular, the AAG group was significantly (P < 0.01) more impaired than the functional gastrointestinal disorder group in the physical functioning and it was significantly more impaired than the control group in all the quality of life subdomains with exception of vitality. Vitamin B12 serum level was a significant (P < 0.04) independent predictor of physical functioning., Conclusions: Patients with AAG have a decreased QoL compared to healthy controls, but in line with that of patients with organic gastrointestinal disorders. Physical component is responsible for worsening QoL. Vitamin B12 supplementation may positively affect patient's perception of body functioning., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research., Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P., Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles., Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P., Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves., Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted., Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%)., Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

The gut-microbiome has been hypothesised as a novel potential target for intervention for schizophrenia. We tested this hypothesis with a systematic review and meta-analysis of studies investigating the efficacy and acceptability of add-on strategies known to affect the gut-microbiome for the treatment of schizophrenia. Following PRISMA guidelines, we searched from inception to August 2019 all the randomised double-blind controlled trials of add-on antibiotics, antimicrobials, pre/probiotics, and faecal transplant in schizophrenia. Primary outcomes were severity of negative symptoms and acceptability of treatment. Data were independently extracted by multiple observers and a random-mixed model was used for the analysis. Heterogeneity was assessed with the I 2 index. We identified 28 eligible trials: 21 investigated antibiotics, 4 antimicrobials (Artemisinin, Artemether, and Sodium Benzoate), 3 pre/probiotics, none faecal transplant. Results showed no effect of D-Cycloserine (10 studies; SMD, -0.16; 95% CI -0.40, 0.08; P = .20; I 2 : 28.2%), Minocycline (7 studies; SMD: -0.35; 95% CI -0.70, 0.00; P = .05, I 2 :77.7%), other antibiotics (2 studies), probiotics alone (1 study), and Artemisinin (1 study) on negative symptoms of schizophrenia when compared to placebo. Limited evidence suggests efficacy on negative symptoms for Sodium benzoate (2 studies; SMD, -0.63; 95%CI -1.03, -0.23; P < .001; I 2 :0%), Artemether (1 study), and probiotics combined with Vitamin D (1 study) when compared to placebo. Acceptability of intervention was similar to placebo. Negative findings were mainly led by antibiotics trials, with paucity of evidence available on pre/probiotics. There is a need of expanding our knowledge on the clinical relevance of gut-microbiome-host interaction in psychosis before engaging in further trials., (Copyright © 2020 Elsevier B.V. All rights reserved.)