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Rosalia Costa,1 Marco Colizzi2 1Gender Identity Development Service, Tavistock and Portman NHS Foundation Trust, Tavistock Centre, 2Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK Abstract: Cross-sex hormonal treatment represents a main aspect of gender dysphoria health care pathway. However, it is still debated whether this intervention translates into a better mental well-being for the individual and which mechanisms may underlie this association. Although sex reassignment surgery has been the subject of extensive investigation, few studies have specifically focused on hormonal treatment in recent years. Here, we systematically review all studies examining the effect of cross-sex hormonal treatment on mental health and well-being in gender dysphoria. Research tends to support the evidence that hormone therapy reduces symptoms of anxiety and dissociation, lowering perceived and social distress and improving quality of life and self-esteem in both male-to-female and female-to-male individuals. Instead, compared to female-to-male individuals, hormone-treated male-to-female individuals seem to benefit more in terms of a reduction in their body uneasiness and personality-related psychopathology and an amelioration of their emotional functioning. Less consistent findings support an association between hormonal treatment and other mental health-related dimensions. In particular, depression, global psychopathology, and psychosocial functioning difficulties appear to reduce only in some studies, while others do not suggest any improvement in these domains. Results from longitudinal studies support more consistently the association between hormonal treatment and improved mental health. On the contrary, a number of cross-sectional studies do not support this evidence. This review provides possible biological explanation vs psychological explanation (direct effect vs indirect effect) for the hormonal treatment-induced better mental well-being. In conclusion, this review indicates that gender dysphoria-related mental distress may benefit from hormonal treatment intervention, suggesting a transient reaction to the nonsatisfaction connected to the incongruent body image rather than a stable psychiatric comorbidity. In this perspective, timely hormonal treatment intervention represents a crucial issue in gender dysphoria individuals’ mental health-related outcome. Keywords: estrogen, testosterone, transsexualism, psychiatry, psychosocial wellbeing

Background: Evidence has been accumulating regarding alterations in components of the endocannabinoid system in patients with psychosis. Of all the putative risk factors associated with psychosis, being at clinical high-risk for psychosis (CHR) has the strongest association with the onset of psychosis, and exposure to childhood trauma has been linked to an increased risk of development of psychotic disorder. We aimed to investigate whether being at-risk for psychosis and exposure to childhood trauma were associated with altered endocannabinoid levels. Method: We compared 33 CHR participants with 58 healthy controls (HC) and collected information about previous exposure to childhood trauma as well as plasma samples to analyse endocannabinoid levels. Results: Individuals with both CHR and experience of childhood trauma had higher N-palmitoylethanolamine (p < 0.001) and anandamide (p < 0.001) levels in peripheral blood compared to HC and those with no childhood trauma. There was also a significant correlation between N-palmitoylethanolamine levels and symptoms as well as childhood trauma. Conclusions: Our results suggest an association between CHR and/or childhood maltreatment and elevated endocannabinoid levels in peripheral blood, with a greater alteration in those with both CHR status and history of childhood maltreatment compared to those with either of those risks alone. Furthermore, endocannabinoid levels increased linearly with the number of risk factors and elevated endocannabinoid levels correlated with the severity of CHR symptoms and extent of childhood maltreatment. Further studies in larger cohorts, employing longitudinal designs are needed to confirm these findings and delineate the precise role of endocannabinoid alterations in the pathophysiology of psychosis. [ABSTRACT FROM AUTHOR]

Background: A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related. Methods: This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes. Results: The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships. Conclusions: The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population. [ABSTRACT FROM AUTHOR]

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.)

Aim: This study assessed whether transition age between adolescence and young adulthood poses a challenge for both patients and mental health services., Methods: We retrospectively examined the baseline characteristics, diagnoses and treatments of 99 individuals aged 16-35 presenting to the PRecocity of Intervention in Adolescent Medicine (PRIMA) transition-age mental health outpatient clinic, Italy, over a 24-month period., Results and Discussion: Most patients were female, aged 20 or younger, employed and did not experience impairment in daily autonomies. About half patients were referred by general practitioners or self-referred, often as initial contact with any adult mental health services, complaining with multiple symptoms (88%), mainly including anxiety, affective disturbances and insomnia. Most of them received a single diagnosis (68%), one out of three being diagnosed with a neurodevelopmental disorder. Patients presenting with anxiety (63% vs. 32%; OR = 3.55, p = 0.01) and affective symptoms (56% vs .23%; OR = 4.26, p = 0.01) and receiving multiple diagnoses (30% vs. 9%; χ 2 (2) = 19.7, p < 0.01) were more likely to be prescribed with psychopharmacological medication at the first visit. At a 6-month follow-up, one in two patients remained in PRIMA, while the others required different services tailored to their specific conditions, especially neurodevelopmental disorders., Conclusion: Findings from this study warrant the need for specialised mental healthcare facilities ensuring timely and high-quality interventions for adolescents transitioning into young adulthood., (© 2024 The Author(s). Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

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.)

Dandy-Walker complex (DWC) consists of a continuum of brain malformations involving the posterior fossa, often leading to psychiatric manifestations during adulthood. We discussed the case of a young woman with Dandy-Walker variant (DWV) and a comorbid complex neuropsychiatric presentation, who was diagnosed with an eating disorder, obsessive-compulsive disorder, and a tic disorder. Afterwards, we conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review reappraising all evidence of psychiatric outcomes in adults with DWC. Overall, 34 studies were eligible for data extraction, comprising 36 patients. Psychiatric profiles were more common among young adult males, with DWC lesions, especially DWV subtype, being often discovered incidentally after admission to mental health inpatient facilities. Most patients were diagnosed with psychosis and bipolar disorder, often comorbid with cognitive impairment. Psychotropic polypharmacy was frequently prescribed, generally leading to complete recovery. Evidence from our case report and systematic review indicates the importance of monitoring long-term psychiatric sequelae among adult patients with DWC malformations.

While insomnia symptoms may be a risk factor for mental disturbances, few studies evaluated "Insomnia Disorder" and its relationship with perinatal psychopathology. Pregnant women were recruited during their last routine assessment before being hospitalized for delivery during the 3rd trimester at the Gynaecological Unit of the University Hospital of Ferrara and Udine, Italy, from January 2022 to January 2023. Our assessment included baseline evaluation (T0), and evaluations at 1 month (T1) and 3 months (T2) in the postpartum period, with specific questionnaires for insomnia disorder, such as Sleep Condition Indicator, mood and anxiety symptoms and psychosocial functioning, such as Edinburgh Postnatal Depression Scale, Mood Disorder Questionnaire, State-Trait Anxiety Inventory, Work and Social Adjustment Scale. At T0, 181 pregnant women were included. Insomnia disorder affected 22.3% at T0, 23.5% at T1 and 16.2% at T2. Women with insomnia disorder at baseline were significantly more affected by concurrent anxiety and depressive symptoms, had higher bipolar diathesis and poorer psychosocial functioning in the perinatal period. Prenatal insomnia disorder predicted anxiety (T0: odds ratio 4.44, p << 0.001; T1: odds ratio 4.009, p = 0.042) and depressive symptoms (T0: odds ratio 2.66, p = 0.015; T1: odds ratio 11.20, p = 0.001; T2: odds ratio 12.50 p = 0.049) in both the prenatal and postnatal period. It also predicted poor psychosocial function during the prenatal (odds ratio 3.55, p = 0.003) and postpartum periods (T1: odds ratio 2.33, p = 0.004). Insomnia disorder is emerging as an important prenatal factor that may contribute to concurrent and postpartum psychopathology., (© 2024 European Sleep Research Society.)

Objectives: To assess the prevalence of neuropsychiatric symptoms 2 years after the COVID-19 acute phase and to identify biobehavioral risk factors., Methods: This 2-year prospective study assessed adult individuals with COVID-19 via face-to-face interview and laboratory testing at onset, and via telephone interview at 2-year follow-up. Data collected included COVID-19 severity and management at onset, as well as depression, anxiety, insomnia, cognitive failure, and fatigue at follow-up using standardized assessment tools., Results: Out of 1,067 screened COVID-19 patients, 230 completed the 2-year follow-up (female, 53.5%; aged>40, 80.9%; native Italian, 94.9%; medical comorbidity, 53.5%; chronic medication, 46.3%; moderate to severe COVID-19, 24.9%; hospital admission, 28.7%; ICU, 5.2%). At follow-up, 9.1% had anxiety, 11.3% depression, 9.1% insomnia, 18.3% cognitive failure, and 39.1% fatigue, of clinical relevance. Headache (OR = 2.49, 95% CI = 1.01-6.16, p = 0.048), dyspnea (OR = 2.55, 95% CI = 1.03-6.31, p = 0.043), and number of symptoms (OR = 1.23, 95% CI = 1.01-1.51, p = 0.047) at onset were associated with anxiety at follow-up; dyspnea at onset was associated with depression at follow-up (OR = 2.80, 95% CI = 1.22-6.41, p = 0.015); number of comorbidities at onset was associated with insomnia at follow-up (OR = 1.48, 95% CI = 1.06-2.08, p = 0.022); female gender (OR = 2.39, 95% CI = 1.14-5.00, p = 0.020) and number of symptoms (OR = 1.20, 95% CI = 1.02-1.42, p = 0.026) at onset was associated with cognitive failure at follow-up; number of comorbidities (OR = 1.33, 95% CI = 1.03-1.73, p = 0.029) and symptoms (OR = 1.19, 95% CI = 1.04-1.37, p = 0.013) and raised interleukin 6 levels ( OR = 4.02, 95% CI = 1.42-11.36, p = 0.009) at onset was associated with fatigue at follow-up., Conclusions: COVID-19 survivors, especially if female, with preexisting health problems, and with a more severe acute phase, may present with long-lasting neuropsychiatric sequalae, urging interventions to sustain recovery particularly in these higher risk individuals.

Background: The diathesis-stress paradigm and the cannabinoid-hypothesis have been proposed as possible pathophysiological models of schizophrenia. However, they have historically been studied independently of each other., Objective: This PRISMA 2020-compliant systematic review aimed at reappraising the interplay between the hypothalamic-pituitary-adrenal (HPA) axis and the endocannabinoid (eCB) system in psychosis- spectrum disorder risk and outcome., Methods: All pathophysiological and outcome clinical studies, concomitantly evaluating the two systems in psychosis-spectrum disorder risk and different stages of illness, were gathered from electronic databases (Pubmed, Web of Science, and Scopus), and discussed., Results: 41 eligible outputs were extracted, focusing on at least a biological measure (9 HPA-related studies: 4 eCB-interventional, 1 HPA-interventional, 1 both HPA-interventional and non-interventional, 3 non-interventional; 2 eCB-related studies: non-interventional), environmental measures only (29 studies: 1 eCB- interventional, 28 non-interventional), and genetic measures (1 study: non-interventional). Independent contributions of aberrancies in the two systems to the physiopathology and outcome of psychosis were confirmed. Also, concomitant alterations in the two systems, either genetically defined (e.g., CNR1 genetic variation), biologically determined (e.g., dysfunctional HPA axis or endocannabinoid signaling), or behaviorally imputed (e.g., cannabis use, stress exposure, and response), were consistently reported in psychosis. Further, a complex biobehavioral perturbation was revealed not only within each system (e.g., cannabis use affecting the eCB tone, stress exposure affecting the HPA axis), but also across the two systems (e.g., THC affecting the HPA axis, childhood trauma affecting the endocannabinoid signaling)., Conclusion: There is a need to concomitantly study the two systems' mechanistic contribution to psychosis in order to establish more refined biological relevance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Psychosocial stressors have been suggested to precipitate psychotic episodes in patients with pre-existing psychosis and otherwise healthy subjects. However, such a risk has never been formally investigated in individuals with autism spectrum disorder (ASD). Sixty-nine autistic adolescents hospitalized for psychotic/manic symptoms (PSY) and other mental health issues (NPSY) over a 9-year period were compared with reference to their previous exposure to psychosocial stressors. ASD diagnoses satisfied the International Classification of Diseases (ICD)-10 criteria. Psychotic/manic symptom assessment followed the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Psychosocial stressor exposure was collected separately at each admission. Preliminarily, univariate between-group comparisons were conducted. Then, a binomial model was adopted to investigate associations with previous exposure to psychosocial stressors. Results were reported with a change in AIC (ΔAIC). PSY patients presented with higher previous exposure to adverse life events (30.43% vs. 6.52%, OR = 6.079 [1.209, 40.926], p = 0.013) and school/work difficulties (30.43% vs. 8.70%, OR = 4.478 [0.984, 23.846], p = 0.034) than NPSY ones. Admissions for psychotic/manic symptoms occurred more likely in the context of family disturbances (OR = 2.275 [1.045, 5.045], p = 0.030) and adverse life events (OR = 3.489 [1.194, 11.161], p = 0.014). The fitted binomial model was found to be significant compared to the random effects model (ΔAIC = -1.962; χ 2 10  = 21.96, p = 0.015), with the risk of presenting psychotic/manic symptoms being increased by family disturbances (z = +4.118) and school/work difficulties (z = +2.455). The results suggest a potential psychosis-inducing effect of psychosocial stressors in ASD, which has clinical and policy implications., (© 2023 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Several scientific contributions have summarized the "lessons learnt" during the coronavirus disease 2019 (COVID-19) pandemic, but only a few authors have discussed what we have learnt on how to design and conduct research during a pandemic. The main intent of this study was to summarize the lessons learnt by an Italian multidisciplinary research group that developed and conducted a longitudinal study on COVID-19 patients infected during the first wave in March 2020 and followed-up for 3 years., Methods: A qualitative research approach embedded into the primary CORonavirus MOnitoRing study (CORMOR) study was developed, according to the the consolidated criteria for reporting qualitative research. Multiple data collection strategies were performed: each member was invited to report the main lessons learnt according to his/her perspective and experience from the study design throughout its conduction. The narratives collected were summarized and discussed in face-to-face rounds. The narratives were then thematically analysed according to their main topic in a list that was resent to all members to check the content and their organization. The list of the final "lessons learnt" has been agreed by all members, as described in a detailed fashion., Results: Several lessons were learnt while designing and conducting a longitudinal study during the COVID-19 pandemic and summarised into ten main themes: some are methodological, while others concern how to conduct research in pandemics/epidemics/infectious disease emergencies., Conclusions: The multidisciplinary approach, which also included patients' perspective, helped us to protect the consistency and quality of the research provided in pandemic times. The lesson learnt suggest that our research approach may benefit from changes in education, clinical practice and policies., (© 2023. The Author(s).)

Introduction: Vaccination against SARS-CoV-2 has been used to reduce the severity of COVID-19 disease and the incidence of new cases. However, a significant proportion of people have shown vaccination hesitancy., Methods: This study explored psychological factors related to vaccination hesitancy in a sample of Italian COVID-19 patients ( N = 54), hospitalized during 2021, after vaccines had been made available and while the vaccination campaign was on-going. Consecutive patients, aged 18 or older, admitted to the hospital with a diagnosis of COVID-19 were assessed with a set of standardized measures., Results: In our sample, 48.1% was not vaccinated and 7.4% died within 6months after hospitalization, with a preponderance of deaths among non-vaccinated patients. Non-vaccinated participants had higher resilience scores at the CD-RISC-10 scale than vaccinated ones (33.6 ± 5.50 vs 28.6 ± 6.61; t40.2=+ 2.94, p = 0.005). No statistically significant differences were found between the two groups for any other measures., Discussion: Higher levels of resilience among non-vaccinated patients may reflect greater identity worth and self-esteem, in turn resulting in a decrease in vaccination likelihood. This finding may have important public health implications, as it indicates that specific psychological aspects, such as resilience, may result in vaccination hesitancy, with implications for hospitalization rates, and thus healthcare costs, as well as loss of lives., Competing Interests: CT has received grants in the last 2 years from Correvio, Biotest, Biomerieux, Gilead, Angelini, Pfizer, Thermofisher, Zambon, Shionogi, Avir Pharma, and Hikma, outside of this work. MCo has been a consultant/advisor to GW Pharma Limited, GW Pharma Italy SRL, and F. Hoffmann-La Roche Limited, outside of this work. 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 Comacchio, Cesco, Martinelli, Garzitto, Bianchi, Innocente, Sozio, Tascini, Balestrieri and Colizzi.)

COVID-19 survivors have been reported to be at risk of long-term neuropsychiatric sequalae; however, prospective evidence in this regard is lacking. We prospectively assessed the occurrence of mental-health-domain-related symptoms over a 24-month period following COVID-19 onset in a cohort of 230 patients. Of them, 36.1% were still presenting with at least one symptom 24 months later. Across the study period, a significant reduction in overall symptoms from the onset was observed ( p < 0.001); however, symptom prevalence was unchanged between the 12- and 24-month follow-ups across most symptomatic domains. At the 24-month follow-up, mental-health-domain-related symptoms only were higher than at the onset and were the most frequently reported symptoms. Dyspnea at the onset predicted both symptoms of psychiatric disorders (OR = 3.26, 95% CI = 1.22-8.70, and p = 0.019) and a lack of concentration and focus (OR = 3.17, 95% CI = 1.40-7.16, and p = 0.005) 24 months post-infection, with the number of comorbidities at the onset also predicting the occurrence of a lack of concentration and focus (OR = 1.52, 95% CI = 1.12-2.08, and p = 0.008). The findings of this study may have important public health implications, as they underlie the fact that COVID-19 survivors are still in need of neuropsychiatric support two years after infection.

The psychoactive properties of cannabis have been known forever. Since 1987, several prospective studies have suggested an increased risk of psychosis among cannabis users, with alternative explanations failing to account for such an effect. A cause-effect relationship has thus been implied. Further evidence has indicated that there is a dose-response relationship, and high-potency cannabis varieties confer the greatest risk of psychosis. As cannabis use has become more common over the last decades, one would expect a related increase in the number of schizophrenia cases. However, evidence in this regard remains equivocal for several reasons, including relying on databases that are not primarily designed to address such question and the issue that solid information regarding the incidence of schizophrenia is a relatively recent acquisition. Recent years have seen the development of online web publications, such as Google Trends and "Our World in Data", where data are explorable and interactable for tracking and comparing trends over specific periods and world regions. By using such databases, we believe that the question whether changes in cannabis use are associated with changes in schizophrenia rates can be answered, at least partly. Therefore, we tested these tools by evaluating trends in cannabis use and both cases and prevalence of schizophrenia in the United Kingdom, one of the countries where the incident rates for psychotic disorder have been suggested to be particularly increased by cannabis consumption. Crossing data from these tools revealed that interest in cannabis has been growing at the country level for over 10 years, with a parallel overlapping raise in psychosis cases and prevalence. Following up on this example, let us think of how many public health opportunities these public resources may offer. The question now is whether public health interventions for the benefit of the general population will follow suit.

COVID-19 pandemic may have affected youth's mental wellbeing. Youth admissions for mental health emergencies over the 2-year period following the COVID-19 outbreak (March 2020-February 2022) were compared to those occurring in the same period of 2018-2020, with reference to individual and clinical data. The study identified 30 admissions in the pre-pandemic period and 65 (+116.7%) in the post-pandemic period, with the latter being younger, less likely to have a personal psychiatric history, and more likely to receive psychopharmacological treatment. A higher likelihood of earlier, ex novo psychiatric manifestations, requiring medication to reach clinical stability, in the post-COVID era, is suggested., Competing Interests: M.C. has been a consultant/advisor to GW Pharma Limited, F. Hoffmann-La Roche Limited, and GW Pharma Italy SRL, outside of this work. All the other authors declare no conflict of interest., (© 2023 The Authors.)

Background: Despite accumulating evidence of an association between stressful life events and psychosis relapse, the extent to which this is a causal relationship remains unclear. We aimed to examine the association between exposure to, and number of, stressful life events after initial psychosis onset and psychosis relapse., Methods: In this 2-year prospective observational study, we recruited individuals with first-episode psychosis, aged 18-65 years, who presented to psychiatric services in south London, UK. Participants were assessed via interview, with additional data obtained from electronic clinical records. Stressful life events were recorded at psychosis onset and during the 2-year follow-up using a brief questionnaire that assesses 12 major life events. Psychosis relapse was defined as inpatient admission because of symptom exacerbation within 2 years from psychosis onset. We examined the time to first psychosis relapse and the number and length of relapses using survival and binomial regression analyses. We used fixed-effects regression and cross-lagged path analysis to examine the directionality of effects and control for unmeasured confounders., Findings: Between April 12, 2002, and July 26, 2013, 256 individuals with first-episode psychosis (100 [39%] female and 156 [61%] male; 16 [6%] Asian, 140 [55%] Black African or Caribbean, 86 [34%] White, and 14 [6%] mixed ethnicity) were recruited, with a mean age of onset of psychosis of 28·06 years (SD 8·03; range 17·21-56·03). 93 (36%) participants experienced at least one relapse during the 2-year follow-up. 253 individuals had all relevant data and were included in analyses. For people exposed to stressful life events after the onset of psychosis, the adjusted hazard (hazard ratio [HR] 2·60, 95% CI 1·63-4·16, p<0·0001), incidence (incidence rate ratio [IRR] 1·87, 1·24-2·80, p=0·0026), and length (IRR 2·53, 1·40-4·67, p=0·0011) of relapse were greater than for those who were unexposed. These relationships were dose dependent (HR 1·36; 1·09-1·69, p=0·0054; incidence IRR 1·26, 1·02-1·53, p=0·023; length IRR 1·52, 1·12-2·12, p=0·0028). Adjusted fixed-effects models showed a higher (odds ratio [OR] 3·82, 1·82-8·00, p=0·0004) and dose-dependent (OR 1·62, 1·18-2·21, p=0·0028) risk of relapse when stressful life events preceded relapse compared with the period when they did not. Cross-lagged path analysis confirmed an effect of stressful life events on the number of subsequent relapses (β=0·66, p=0·0055) that was dose dependent (β=0·29, p=0·029), but it did not show an effect of relapses on subsequent risk or number of stressful life events., Interpretation: These results provide converging evidence of a causal effect of stressful life events on the risk of relapse in psychosis. They suggest that there is a need to develop interventions at the individual and health-service level that could mitigate the harmful effects of stressful life events., Funding: National Institute for Health Research, UK., Competing Interests: Declaration of interests SB has received support from the National Institute for Health Research (NIHR) Clinician Scientist Award (NIHR CS-11-001) and the Medical Research Council (MR/J012149/1). TS has received support from the Wellcome Trust Postdoctoral Fellowship (grant numbers 218641/Z/19/Z). RM has received support from the Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, UK. AEC has received support from the NARSAD Young Investigator Grant awarded by the Brain & Behavior Research Foundation (28336) and funded by the Evelyn Toll Family Foundation. MC has been a consultant or advisor to GW Pharma, GW Pharma Italy, and F Hoffmann-La Roche, outside of this work. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Mentalization is the ability to use internal mental states to manage and understand one's own and others' behavior. Inefficient mentalization has been associated to poor neuropsychological outcomes, including substance use disorder (SUD) and addiction. However, studies primarily investigating mentalization in SUD are lacking., Methods: Using the Reflective Functioning Questionnaire (RFQ), the Measurements in the Addictions for Triage and Evaluation, version 2.1 (MATE-IT-2.1), and the Mini International Neuropsychiatric Interview, 7th edition (MINI-7), an outpatient assessment investigated inefficient mentalization (i.e., 'hypo-mentalization' or 'uncertainty': concrete thinking with poor attribution of mental states; 'hyper-mentalization' or 'certainty': rigid and biased attribution of mental states) and socio-demographic and clinical characteristics, including SUD-related symptoms and any other psychiatric comorbidity, among opioid addiction (OA) patients in Opioid Agonist Treatment (OAT)., Results: Thirty-seven consecutive OA patients in OAT (female, 45.9 %; age, M ± SD, 24.3 ± 3.55) were recruited. Patients' mentalization differed from normative data, in terms of higher uncertainty and lower certainty scores. Also, higher uncertainty score was found among younger patients and in those with the most severe SUD in terms of craving and need for care. Finally, lower certainty score was found in those with a more severe substance abuse, previous contacts with pediatric mental-health services, and receiving a therapeutic community support., Conclusions: OA patients with inefficient mentalization present with a higher burden in terms of SUD severity, comorbidities, psychosocial disabilities, and service use, with important public health implications. Interventions targeting mentalization may have positive repercussions in preventing SUD, mitigating its severity, and containing its healthcare and social costs., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.C. has been a consultant/advisor to GW Pharma Limited, GW Pharma Italy SRL, and F. Hoffmann-La Roche Limited, outside of this work. All the other authors declare no conflict of interest., (© 2023 The Author(s).)

This study assessed changes in revolving-door (RD) mental health hospitalizations during the COVID-19 pandemic. A 5-year retrospective hospital chart review was performed, collecting revolving-door hospitalization, sociodemographic, and clinical data. Out of 1036 patients, 5.69% had RD hospitalizations, which accounted for 10.38% of all recorded hospitalizations. Further, a higher number of RD hospitalizations occurred following the pandemic outbreak, which is unlikely to have been a result of the confounding effect of trimester and month of hospitalization. Finally, several sociodemographic and clinical characteristics recurred more frequently in the context of RD hospitalizations, such as being younger, being compulsorily admitted, being an absconding patient, and being referred by a public service. Certain diagnostic categories occurred more frequently among RD hospitalizations, including psychotic, personality, and substance use disorders, as well as intellectual disability. Patients with specific characteristics are more likely to incur in RD hospitalizations, requiring the implementation of supportive treatment plans, especially following the pandemic outbreak.

Neurodevelopmental disorders (NDDs) encompass a group of complex conditions with onset during the early developmental period. Such disorders are frequently associated with a number of neuropsychiatric features, the most prevalent ones being autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disability, communication and specific learning disorders, and motor disorders. These conditions are characterized by wide genetic and clinical variability, and although they were previously conceptualized as childhood-limited disorders, NDDs are progressively being recognized as persistent conditions with a potentially relevant impact on the quality of life and overall functioning during adult life. In addition, emerging evidence seems to point towards the hypothesis of a neurodevelopmental continuum, according to which NNDs could portray different time-dependent outcomes, depending on the severity of the altered brain development. Despite representing lifelong phenotypes, they are often not promptly identified and/or managed in adulthood. In this regard, specific guidelines on clinical and therapeutic approaches for these conditions have not yet been delineated. In this view, future research investigations should be encouraged to broaden available knowledge, characterize the clinical course of NDDs across an individual's lifespan, and better understand the patterns of aging-related concerns in adults with an NDD diagnosis. Additionally, considering the difficulties many young adults encounter while transitioning from childhood to adult mental health services, new, specific programs should be developed and existing programs should be implemented to improve the transition process and for the management of NDDs in adulthood.