Prenatal insomnia disorder may predict concurrent and postpartum psychopathology: A longitudinal study.

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.

Lessons learnt while designing and conducting a longitudinal study from the first Italian COVID-19 pandemic wave up to 3 years.

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.

Normalization of mediotemporal and prefrontal activity, and mediotemporal-striatal connectivity, may underlie antipsychotic effects of cannabidiol in psychosis.

BACKGROUND: Recent evidence suggests that cannabidiol (CBD), a non-intoxicating ingredient present in cannabis extract, has an antipsychotic effect in people with established psychosis. However, the effect of CBD on the neurocognitive mechanisms underlying psychosis is unknown. METHODS: Patients with established psychosis on standard antipsychotic treatment were studied on separate days at least one week apart, to investigate the effects of a single dose of orally administered CBD (600 mg) compared to a matched placebo (PLB), using a double-blind, randomized, PLB-controlled, repeated-measures, within-subject cross-over design. Three hours after taking the study drug participants were scanned using a block design functional magnetic resonance imaging (fMRI) paradigm, while performing a verbal paired associate learning task. Fifteen psychosis patients completed both study days, 13 completed both scanning sessions. Nineteen healthy controls (HC) were also scanned using the same fMRI paradigm under identical conditions, but without any drug administration. Effects of CBD on brain activation measured using the blood oxygen level-dependent hemodynamic response fMRI signal were studied in the mediotemporal, prefrontal, and striatal regions of interest. RESULTS: Compared to HC, psychosis patients under PLB had altered prefrontal activation during verbal encoding, as well as altered mediotemporal and prefrontal activation and greater mediotemporal-striatal functional connectivity during verbal recall. CBD attenuated dysfunction in these regions such that activation under its influence was intermediate between the PLB condition and HC. CBD also attenuated hippocampal-striatal functional connectivity and caused trend-level symptom reduction in psychosis patients. CONCLUSIONS: This suggests that normalization of mediotemporal and prefrontal dysfunction and mediotemporal-striatal functional connectivity may underlie the antipsychotic effects of CBD.

Delta-9-tetrahydrocannabinol increases striatal glutamate levels in healthy individuals: implications for psychosis.

The neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P = 0.027). Furthermore, compared to individuals who were not sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P 7= 0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r = -0.55; P = 0.026) and higher previous cannabis exposure (r = 0.52; P = 0.040) were associated with a higher Δ9-THC-induced Glx increase. These results suggest that an increase in striatal glutamate levels may underlie acute cannabis-induced psychosis while lower baseline levels may be a marker of greater sensitivity to its acute psychotomimetic effects and may have important public health implications.

Should we be concerned about stigma and discrimination in people at risk for psychosis? A systematic review.

BACKGROUND: Previous studies have provided initial evidence that people at risk for psychosis (PR) suffer from stigma and discrimination related to their condition. However, no study has systematically reviewed stigma and discrimination associated with being at PR and the potential underlying mechanisms. METHODS: This work aimed to systematically review all studies addressing stigma and discrimination in PR people in order to assess: (1) the occurrence of this phenomenon and its different components (public, internalized, perceived, and labeling-related), (2) whether stigma affects outcomes of the PR state, and (3) whether other factors modulate stigma among PR individuals. RESULTS: The reviewed studies (n = 38) widely differ in their design, methodological quality, and populations under investigation, thus limiting direct comparison of findings. However, converging evidence suggests that the general public endorses stigmatizing attitudes towards PR individuals, and that this is more frequent in people with a low educational level or with no direct experience of the PR state. PR individuals experience more internalized stigma and perceive more discrimination than healthy subjects or patients with non-psychotic disorders. Further, PR labeling is equally associated with both positive (e.g. validation and relief) and negative effects (e.g. status loss and discrimination). Moreover, stigma increases the likelihood of poor outcome, transition to full-psychosis, disengagement from services, and family stigma among PR individuals. Finally, very limited evidence awaiting replication supports the efficacy of cognitive therapies in mitigating the negative effects of stigma. CONCLUSIONS: Evidence confirms previous concerns about stigma and its negative consequences for PR individuals, thus having important public health implications.

Differential sensitivity to the acute psychotomimetic effects of delta-9-tetrahydrocannabinol associated with its differential acute effects on glial function and cortisol.

BACKGROUND: Cannabis use has been associated with psychosis through exposure to delta-9-tetrahydrocannabinol (Δ9-THC), its key psychoactive ingredient. Although preclinical and human evidence suggests that Δ9-THC acutely modulates glial function and hypothalamic-pituitary-adrenal (HPA) axis activity, whether differential sensitivity to the acute psychotomimetic effects of Δ9-THC is associated with differential effects of Δ9-THC on glial function and HPA-axis response has never been tested. METHODS: A double-blind, randomized, placebo-controlled, crossover study investigated whether sensitivity to the psychotomimetic effects of Δ9-THC moderates the acute effects of a single Δ9-THC dose (1.19 mg/2 ml) on myo-inositol levels, a surrogate marker of glia, in the Anterior Cingulate Cortex (ACC), and circadian cortisol levels, the key neuroendocrine marker of the HPA-axis, in a set of 16 healthy participants (seven males) with modest previous cannabis exposure. RESULTS: The Δ9-THC-induced change in ACC myo-inositol levels differed significantly between those sensitive to (Δ9-THC minus placebo; M = -0.251, s.d. = 1.242) and those not sensitive (M = 1.615, s.d. = 1.753) to the psychotomimetic effects of the drug (t(14) = 2.459, p = 0.028). Further, the Δ9-THC-induced change in cortisol levels over the study period (baseline minus 2.5 h post-drug injection) differed significantly between those sensitive to (Δ9-THC minus placebo; M = -275.4, s.d. = 207.519) and those not sensitive (M = 74.2, s.d. = 209.281) to the psychotomimetic effects of the drug (t(13) = 3.068, p = 0.009). Specifically, Δ9-THC exposure lowered ACC myo-inositol levels and disrupted the physiological diurnal cortisol decrease only in those subjects developing transient psychosis-like symptoms. CONCLUSIONS: The interindividual differences in transient psychosis-like effects of Δ9-THC are the result of its differential impact on glial function and stress response.

Jumping to conclusions at first onset of psychosis predicts longer admissions, more compulsory admissions and police involvement over the next 4 years: the GAP study.

BACKGROUND: Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case-control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years. METHODS: One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning 'Beads' Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment - the Mental Health Act (MHA) - and inpatient days). RESULTS: FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA [adjusted OR 15.62, 95% confidence interval (CI) 2.92-83.54, p = 0.001], require intervention by the police (adjusted OR 14.95, 95% CI 2.68-83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91-13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions. CONCLUSIONS: JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.

The Neural Substrate of Reward Anticipation in Health: A Meta-Analysis of fMRI Findings in the Monetary Incentive Delay Task.

The monetary incentive delay task breaks down reward processing into discrete stages for fMRI analysis. Here we look at anticipation of monetary gain and loss contrasted with neutral anticipation. We meta-analysed data from 15 original whole-brain group maps (n = 346) and report extensive areas of relative activation and deactivation throughout the whole brain. For both anticipation of gain and loss we report robust activation of the striatum, activation of key nodes of the putative salience network, including anterior cingulate and anterior insula, and more complex patterns of activation and deactivation in the central executive and default networks. On between-group comparison, we found significantly greater relative deactivation in the left inferior frontal gyrus associated with incentive valence. This meta-analysis provides a robust whole-brain map of a reward anticipation network in the healthy human brain.

Correction to: The Neural Substrate of Reward Anticipation in Health: A Meta-Analysis of fMRI Findings in the Monetary Incentive Delay Task.

The members of MTAC were removed from the author group and full list are shown in the Acknowledgements section. Also, members "Roee, A" and "Van Amselvoort, T" should be "Admon, R" and "Van Amelsvoort, T", respectively. The original article has been corrected.

Cannabis and psychosis: what do we know and what should we do?

It is now incontrovertible that heavy use of cannabis increases the risk of psychosis. There is a dose-response relationship and high potency preparations and synthetic cannabinoids carry the greatest risk. It would be wise to await the outcome of the different models of legalisation that are being introduced in North America, before deciding whether or not to follow suit. Declaration of interest None.

Psychological Support, Puberty Suppression, and Psychosocial Functioning in Adolescents with Gender Dysphoria.

INTRODUCTION: Puberty suppression by gonadotropin-releasing hormone analogs (GnRHa) is prescribed to relieve the distress associated with pubertal development in adolescents with gender dysphoria (GD) and thereby to provide space for further exploration. However, there are limited longitudinal studies on puberty suppression outcome in GD. Also, studies on the effects of psychological support on its own on GD adolescents' well-being have not been reported. AIM: This study aimed to assess GD adolescents' global functioning after psychological support and puberty suppression. METHODS: Two hundred one GD adolescents were included in this study. In a longitudinal design we evaluated adolescents' global functioning every 6 months from the first visit. MAIN OUTCOME MEASURES: All adolescents completed the Utrecht Gender Dysphoria Scale (UGDS), a self-report measure of GD-related discomfort. We used the Children's Global Assessment Scale (CGAS) to assess the psychosocial functioning of adolescents. RESULTS: At baseline, GD adolescents showed poor functioning with a CGAS mean score of 57.7 ± 12.3. GD adolescents' global functioning improved significantly after 6 months of psychological support (CGAS mean score: 60.7 ± 12.5; P < 0.001). Moreover, GD adolescents receiving also puberty suppression had significantly better psychosocial functioning after 12 months of GnRHa (67.4 ± 13.9) compared with when they had received only psychological support (60.9 ± 12.2, P = 0.001). CONCLUSION: Psychological support and puberty suppression were both associated with an improved global psychosocial functioning in GD adolescents. Both these interventions may be considered effective in the clinical management of psychosocial functioning difficulties in GD adolescents.

Biobehavioral Interactions between Endocannabinoid and Hypothalamicpituitary- adrenal Systems in Psychosis: A Systematic Review.

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.

Tic-Related Obsessive-Compulsive and Eating Disorders in Dandy-Walker Variant: A Case Report and Systematic Reappraisal of Psychiatric Profiles.

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.

Prevalence and risk factors for depression in factitious disorder: a systematic review.

Objective: Factitious disorder is characterized by a pattern of abnormal behavior in which patients deliberately produce, falsify, or exaggerate physical and/or psychological symptoms that have no, or little, organic basis, to assume the sick role. In the context of a factitious disorder, depression can be both a feigned disease and an associated comorbidity. We performed a systematic review to provide an overview of the relationship between factitious disorder and depression, describe the prevalence of depression in factitious disorder, and identify factors that can contribute to the development of depression in patients suffering from factitious disorder. Methods: A literature search was performed using the electronic databases PubMed, EMBASE and Cochrane Library following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were eligible for inclusion in this review if they investigated factitious disorder or Munchausen Syndrome with comorbid depression. Results: Depression was found to be highly prevalent in factitious disorder, affecting around 30% of the samples. Risk factors for depression in factitious disorder included having suffered from childhood and adulthood traumatic experiences and having a history of psychosocial problems. Conclusion: The treatment of factitious disorder is challenging and requires a multidisciplinary team approach. Given the high levels of depression in patients with factitious disorder, we recommend to always screen for depression once a factitious disorder is diagnosed.

COVID-19-induced neuropsychiatric symptoms can persist long after acute infection: a 2-year prospective study of biobehavioral risk factors and psychometric outcomes.

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.

Hormonal treatment reduces psychobiological distress in gender identity disorder, independently of the attachment style.

INTRODUCTION: Gender identity disorder may be a stressful situation. Hormonal treatment seemed to improve the general health as it reduces psychological and social distress. The attachment style seemed to regulate distress in insecure individuals as they are more exposed to hypothalamic-pituitary-adrenal system dysregulation and subjective stress. AIM: The objectives of the study were to evaluate the presence of psychobiological distress and insecure attachment in transsexuals and to study their stress levels with reference to the hormonal treatment and the attachment pattern. METHODS: We investigated 70 transsexual patients. We measured the cortisol levels and the perceived stress before starting the hormonal therapy and after about 12 months. We studied the representation of attachment in transsexuals by a backward investigation in the relations between them and their caregivers. MAIN OUTCOME MEASURES: We used blood samples for assessing cortisol awakening response (CAR); we used the Perceived Stress Scale for evaluating self-reported perceived stress and the Adult Attachment Interview to determine attachment styles. RESULTS: At enrollment, transsexuals reported elevated CAR; their values were out of normal. They expressed higher perceived stress and more attachment insecurity, with respect to normative sample data. When treated with hormone therapy, transsexuals reported significantly lower CAR (P < 0.001), falling within the normal range for cortisol levels. Treated transsexuals showed also lower perceived stress (P < 0.001), with levels similar to normative samples. The insecure attachment styles were associated with higher CAR and perceived stress in untreated transsexuals (P < 0.01). Treated transsexuals did not expressed significant differences in CAR and perceived stress by attachment. CONCLUSION: Our results suggested that untreated patients suffer from a higher degree of stress and that attachment insecurity negatively impacts the stress management. Initiating the hormonal treatment seemed to have a positive effect in reducing stress levels, whatever the attachment style may be.

Where Do Neurodevelopmental Disorders Go? Casting the Eye Away from Childhood towards Adulthood.

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.

Can we interrogate public databases to fill critical gaps in mental health epidemiology? Testing the association between cannabis and psychosis in the UK as an example.

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.

Questioning the role of palmitoylethanolamide in psychosis: a systematic review of clinical and preclinical evidence.

Introduction: The endocannabinoid (eCB) system disruption has been suggested to underpin the development of psychosis, fueling the search for novel, better-tolerated antipsychotic agents that target the eCB system. Among these, palmitoylethanolamide (PEA), an N-acylethanolamine (AE) with neuroprotective, anti-inflammatory, and analgesic properties, has drawn attention for its antipsychotic potential. Methods: This Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-compliant systematic review aimed at reappraising all clinical and preclinical studies investigating the biobehavioral role of PEA in psychosis. Results: Overall, 13 studies were eligible for data extraction (11 human, 2 animal). Observational studies investigating PEA tone in psychosis patients converged on the evidence for increased PEA plasma (6 human) and central nervous system (CNS; 1 human) levels, as a potential early compensatory response to illness and its severity, that seems to be lost in the longer-term (CNS; 1 human), opening to the possibility of exogenously supplementing it to sustain control of the disorder. Consistently, PEA oral supplementation reduced negative psychotic and manic symptoms among psychosis patients, with no serious adverse events (3 human). No PEA changes emerged in either preclinical psychosis model (2 animal) studied. Discussion: Evidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder. Systematic review registration: https://doi.org/10.17605/OSF.IO/AFMTK.

Prevalence and Risk Factors for Absconding from an Open-Door, No-Restraint Inpatient Psychiatric Unit: A Single-Center Study in Italy.

Absconding from inpatient psychiatric services has been associated with poor outcomes, putting the patient and community at risk and prolonging the recovery process. A retrospective study investigated the absconding rates and risk factors among patients admitted to an open-door, no-restraint inpatient psychiatric unit. Overall, the absconding rate was 4.5%, and the relative risk of absconding was higher for male, younger, and non-Caucasian patients as well as for those who had already absconded, were unknown to health services, compulsorily admitted, admitted for substance abuse, and in the first days of hospitalization. The findings of this study may have important public health implications.