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ObjectiveFactitious 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.MethodsA 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.ResultsDepression 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.ConclusionThe 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.

Abstract 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.

Background: In the post-COVID era an increase in Emergency Department (ED) mental health assessments has been consistently reported among youth populations. Methods: Pediatric ED mental health assessments in the 2 years following the COVID-19 pandemic (March 2020-February 2022) were compared to those in the immediately preceding same period (March 2018-February 2020), in terms of rates and risk profiles. Results: During the pre-pandemic and post-pandemic periods, 158 and 268 ED accesses were counted respectively, and an overall 1.64 (95 % CI: 1.34–1.99) monthly IRR was estimated. During the post-pandemic period, youth accessing ED were less likely to have a personal history of psychiatric disorders (OR: 0.49; 95 % CI: 0.28–0.86) and to receive an extemporaneous administration of psychopharmacological therapy in ED (OR: 0.28; 95 % CI: 0.14–0.57), despite being more frequently discharged from ED with a background psychopharmacological therapy in place (OR: 2.02; 95 % CI: 1.02–4.01). Finally, during the post-pandemic period, an increase in ED accesses for eating disorder (OR: 2.77; 95 % CI: 1.49–5.13) and suicidal thoughts-self-harm (OR: 2.00; 95 % CI: 1.07–3.74) was observed, when compared to ED access for anxiety-agitation. Conclusions: This report suggests higher rates of post-COVID pediatric ED mental health assessments, especially for eating disorder and suicide risk, with a preponderance of youth whose ED access may be their first mental health specialist contact.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social communication and restricted or repetitive behavior and interests. Psychic distress is common among individuals with ASD, especially in its milder form (level 1), with anxiety and depression being the most common types. Recent research has identified neuroinflammation and gut dysbiosis as potential neurobiological mechanisms underlying ASD. Palmitoylethanolamide (PEA), an endocannabinoid (eCB)-like compound, has shown promise in modulating such mechanisms and may thus have therapeutic implications for ASD. To date, no clinical trial has evaluated the efficacy of PEA in adults with ASD. This 12-week open-label study will assess the feasibility, tolerability, safety, and efficacy of ultramicronized PEA (um-PEA) in treating symptoms of psychic distress, such as anxiety and depression, in adults with level 1 ASD. Secondary research endpoints will include um-PEA’s effects on levels of personal autonomy and neurocognitive and interpersonal function. From a biological point of view, this study will assess um-PEA’s effects on inflammatory markers, the metabolic profile, eCB system modulation, and microbial composition as potential mechanisms of action for its therapeutic effect. In conclusion, this study will investigate a novel approach to the treatment of adults presenting with psychic distress in the context of level 1 ASD. The results may provide valuable insight into the use of um-PEA as a treatment option for ASD adults, addressing a significant unmet clinical need.

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.

IntroductionVaccination 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.MethodsThis 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.ResultsIn 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.DiscussionHigher 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.

IntroductionThe 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.MethodsThis 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.ResultsOverall, 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.DiscussionEvidence supports PEA signaling as a potential psychosis biomarker, also indicating a therapeutic role of its supplementation in the disorder.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/AFMTK.

Workplaces can be associated with occupational stress, detrimental consequences in terms of loss of health and reduced psychosocial well-being. Importantly, employees may be particularly at risk of poorer well-being during times of adversity at work, when not able to apply adaptive coping strategies and adopt a more empathetic approach. This study aimed to develop a scale to estimate occupational stress both in terms of situational and individual components, by performing item selection, internal reliability assessment, and investigation of the ceiling/floor effect. The target population consisted of veterinarians (n = 116), based on evidence of high risk of occupational stress and related mental distress. Out of twenty initial candidate entries, exploratory factor analysis retained fifteen items consisting of three domains related to occupational stress, copying strategies, and empathy (SCOPE). The SCOPE scale demonstrated good internal consistency as a whole (Cronbach’s alpha = 0.79) and when considering the three subscales (stress, 0.85; coping, 0.77; and empathy, 0.71). On a possible range from 15 (worst adjustment) to 75 (best adjustment), the sample mean performance was 51.68 (SD, 8.50). Preliminary evidence indicated that the SCOPE questionnaire may reveal differential effects of type of work on levels of occupational stress and related coping and empathy skills.

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.

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.

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 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.

Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate β-amyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.

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.

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.

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.

COVID-19 pandemic may affect children's mental health. Children

Abstract Background Similar to other health care sectors, mental health has moved towards the secondary prevention, with the effort to detect and treat mental disorders as early as possible. However, converging evidence sheds new light on the potential of primary preventive and promotion strategies for mental health of young people. We aimed to reappraise such evidence. Methods We reviewed the current state of knowledge on delivering promotion and preventive interventions addressing youth mental health. Results Half of all mental disorders start by 14 years and are usually preceded by non-specific psychosocial disturbances potentially evolving in any major mental disorder and accounting for 45% of the global burden of disease across the 0–25 age span. While some action has been taken to promote the implementation of services dedicated to young people, mental health needs during this critical period are still largely unmet. This urges redesigning preventive strategies in a youth-focused multidisciplinary and trans-diagnostic framework which might early modify possible psychopathological trajectories. Conclusions Evidence suggests that it would be unrealistic to consider promotion and prevention in mental health responsibility of mental health professionals alone. Integrated and multidisciplinary services are needed to increase the range of possible interventions and limit the risk of poor long-term outcome, with also potential benefits in terms of healthcare system costs. However, mental health professionals have the scientific, ethical, and moral responsibility to indicate the direction to all social, political, and other health care bodies involved in the process of meeting mental health needs during youth years.

Background: Long-term benzodiazepine (BDZ)/Z-drug use, which is a risk factor for dependence, is frequent in neuropsychiatric conditions, especially emotional disorders. Also, BDZ/Z-drug misuse is associated with increased emotion dysregulation symptoms. This study aimed to investigate neuropsychiatric distress in patients with BZD/Z-drug use disorder, with particular attention to emotional symptoms.Methods: Forty-two patients hospitalized for BZD/Z-drug use disorder (males/females= 20/22) were enrolled and dichotomized into a high-dose and a low-dose BZD/Z-drug user group. Neuropsychiatric distress was measured using standardized measures. The relationship between symptom profiles and BZD/Z-drug use disorder severity was explored using t-tests and negative binomial regression analyses.Results: Twenty-seven patients (61.9%) presented with one or more psychiatric disorders, mostly an emotional disorder. Ten patients had a lifetime history of suicide attempt(s) (23.8%), while 11 presented recent suicidal ideation (26.2%), which resulted in suicidal behavior in 2 cases. High rates of depression, anxiety, and emotion dysregulation were reported. The high-dose BZD/Z-drug user group presented with higher depressive symptoms (p = 0.016) and emotion dysregulation (p = 0.044) than the low-dose BZD/Z-drug user group. Further, the higher the depressive symptomatology, the more severe was the BZD/Z-drug abuse (p = 0.028).Limitations: Long-term patterns of BDZ/Z-drug use disorder among patients with emotional disorders and the role of other potential risk factors, such as gender, other substance use disorder, and personality disorders, need further investigation in larger samples.Conclusions: This study showed high emotional symptoms among patients with BZD/Z-drug use disorder, with severe depression being associated with a more severe BZD/Z-drug dependence.

Being particularly vulnerable to the pro-psychotic effects of cannabinoid exposure, autism spectrum individuals present with an increased risk of psychosis, which may be passed on to their own children. More specifically, cannabis exposure among autism spectrum individuals seems to exert disruptive epigenetic effects that can be intergenerationally inherited in brain areas which play a critical role in schizophrenia pathophysiology. Additionally, because of such cannabinoid-induced epigenetic effects, autism candidate genes present with bivalent chromatin markings which make them more vulnerable to subsequent disruption, possibly leading to psychosis onset later in life. Thus, findings support a developmental trajectory between autism and psychosis, as per endocannabinoid system modulation. However, such evidence has not received the attention it deserves.

Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA’s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.

Cannabis use during the critical neurodevelopmental period of adolescence, may lead to brain structural, functional, and histological alterations that may underpin some of the longer-term behavioral and psychological harms associated with it. The endocannabinoid system performs a key regulatory and homeostatic role, that undergoes developmental changes during adolescence making it potentially more susceptible to the effects of exposure to cannabis during adolescence. Here, we synthesize evidence from human studies of adolescent cannabis users showing alterations in cognitive performance as well as in brain structure and function with relevant preclinical evidence to summarize the current state of knowledge. We also focus on the limited evidence that speaks to the hypothesis that cannabis use during adolescence, may pose a greater risk than use during adulthood, identify gaps in current evidence and suggest directions for new research. Existing literature is consistent with the association of cannabis use during adolescence and neurological changes. Adolescence cannabis users show altered functional connectivity within known functional circuits, that may underlie inefficient recruitment of brain regions, as largely increased functional activation has been observed compared to controls. This disruption in some cases may contribute to the development of adverse mental health conditions; increasing the chances or accelerating the onset, of their development. Preclinical evidence, further supports disruption from cannabis use being specific to the developmental period. Future studies are required to better investigate adolescent cannabis use with more accuracy using better defined groups or longitudinal studies and examine the permanency of these changes following caseation of use. Furthermore, research is required to identify heritable risk factors to cannabis use. There is a need for caution when considering the therapeutic potential of cannabis for adolescence and particularly in public discourse leading to potential trivialization of possible harm from cannabis use in adolescence. Current evidence indicates that adolescence is a sensitive period during which cannabis use may result in adverse neurocognitive effects that appear to show a level of permanency into adulthood.

In early 2020, a novel coronavirus (SARS-CoV-2) leading to a potentially fatal condition was discovered. Since then, the 2019 coronavirus disease (COVID-19) has spread worldwide becoming a pandemic. Beyond the risks strictly related to the infection, concerns have been expressed for the psychological impact that COVID-19 may have, especially on vulnerable individuals with pre-existing mental health conditions. Somatic symptom disorder (SSD) is characterized by a dysfunctional preoccupation with physical symptoms leading to excessive and unnecessary healthcare utilization. Despite being quite common, such condition remains underrecognized. We report a detailed clinical case of a 16 years old adolescent, who presented with a history suggestive of COVID-19 infection and associated psychological distress. Despite testing negative for the presence of SARS-CoV-2, his extreme and persisting health preoccupations required an inpatient admission to the Child and Adolescent Neuropsychiatric Unit. He responded rapidly to a low dose of antipsychotic and an antidepressant. Based on his medical history and current presentation, he received a diagnosis of SSD. When COVID-19-like symptoms occur, we highlight the importance of differentially diagnosing a possible exacerbation of a pre-existing SSD, triggered by fear of being infected. This may help preventing further burden to the healthcare system.

Research evidence suggests a dose–response relationship for the association between cannabis use and risk of psychosis. Such relationship seems to reflect an increased risk of psychosis not only as a function of frequent cannabis use, but also of high-potency cannabis use in terms of concentration of Δ-9-tetrahydrocannabinol (Δ9-THC), its main psychoactive component. This finding would be in line with the evidence that Δ9-THC administration induces transient psychosis-like symptoms in otherwise healthy individuals. Conversely, low-potency varieties would be less harmful because of their lower amount of Δ9-THC and potential compresence of another cannabinoid, cannabidiol (CBD), which seems to mitigate Δ9-THC detrimental effects. A growing body of studies begins to suggest that CBD may have not only protective effects against the psychotomimetic effects of Δ9-THC but even therapeutic properties on its own, opening new prospects for the treatment of psychosis. Despite being more limited, evidence of the effects of cannabis on cognition seems to come to similar conclusions, with increasing Δ9-THC exposure being responsible for the cognitive impairments attributed to recreational cannabis use while CBD preventing such effects and, when administered alone, enhancing cognition. Molecular evidence indicates that Δ9-THC and CBD may interact with cannabinoid receptors with almost opposite mechanisms, with Δ9-THC being a partial agonist and CBD an inverse agonist/antagonist. With the help of imaging techniques, pharmacological studies in vivo have been able to show opposite effects of Δ9-THC and CBD also on brain function. Altogether, they may account for the intoxicating and therapeutic effects of cannabis on psychosis and cognition.

Mosaic trisomy 20 is a genetic condition in which three chromosomes 20 are found in some cells. Its clinical phenotype seems to be highly variable, with most features not reported across all individuals and not considered pathognomonic of the condition. Limited and recent evidence indicates that neuropsychiatric manifestations may be more present in the context of trisomy 20 than was once thought. Here, we present a case of a 14-year-old female adolescent of White/Caucasian ethnicity with mosaic trisomy 20, who was admitted twice to an inpatient Child and Adolescent Neuropsychiatry Unit for persisting self-injury and suicidal ideation. A severe and complex neuropsychiatric presentation emerged at the cognitive, emotional, and behavioral levels, including mild neurodevelopmental issues, isolation, socio-relational difficulties, depressed mood, temper outbursts, irritability, low self-esteem, lack of interest, social anxiety, panic attacks, self-cutting, and low-average-range and heterogeneous intelligence quotient profile. Particularly, the patient was considered at high risk of causing harm, mainly to self, and appeared to be only partially responsive to medication, even when polypharmacy was attempted to improve clinical response. Except for school bullying, no other severe environmental risk factors were present in the patient’s history. The patient received a diagnosis of disruptive mood dysregulation disorder.

High doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, have been shown to have anxiogenic effects. Additionally, THC effects have been shown to be modulated by genotype, including the single nucleotide polymorphism (SNP) rs1130233 at the protein kinase AKT1 gene, a key component of the dopamine signalling cascade. As such, it is likely that epigenetic methylation around this SNP may affect AKT gene expression, which may in turn impact on the acute effects of THC on brain function. We investigated the genetic (AKT1 rs1130233) and epigenetic modulation of brain function during fear processing in a 2-session, double-blind, cross-over, randomized placebo-controlled THC administration, in 36 healthy males. Fear processing was assessed using an emotion (fear processing) paradigm, under functional magnetic resonance imaging (fMRI). Complete genetic and fMRI data were available for 34 participants. THC caused an increase in anxiety and transient psychotomimetic symptoms and para-hippocampal gyrus/amygdala activation. Number of A alleles at the AKT1 rs1130233 SNP, and percentage methylation at the CpG11–12 site, were independently associated with a greater effect of THC on activation in a network of brain regions including left and right parahippocampal gyri, respectively. AKT1 rs1130233 moderation of the THC effect on left parahippocampal activation persisted after covarying for methylation percentage, and was partially mediated in sections of the left parahippocampal gyrus/hippocampus by methylation percentage. These results may offer an example of how genetic and epigenetic variations influence the psychotomimetic and neurofunctional effects of THC.

Youth with Attention-Deficit Hyperactivity Disorder (ADHD) may suffer from comorbid difficulties, such as anxiety–depressive symptoms, social withdrawal, and somatic complaints. Although stimulants remain the ADHD cornerstone treatment, mental fatigue, school problems and low self-esteem may persist, often being the most unacceptable symptoms for these patients. We present two cases of adolescents (14 and 15 years old) with methylphenidate-treated ADHD, where cognitive fatigability, depressive thoughts, anxiety, irritability, and poor social relationships remained. Based on clinical observation and the completion of parent and child rating scales, the aforementioned manifestations appeared to progressively reduce by the time of the subsequent control visits planned 1, 3, and 5 months after, following the use of vortioxetine (up to 10 mg/day) as add-on therapy to methylphenidate. No significant side effects were reported in both cases in a follow-up period of 3 months, also supporting the stability of the observed clinical improvement. Vortioxetine monotherapy has already been tested for the treatment of anxiety–depressive symptoms in youth, as well as ADHD in adulthood. The cases presented here suggest that vortioxetine could also be an effective option for ADHD treatment in childhood and adolescence, warranting further investigation of its potential benefits as both a monotherapy and adjunctive therapy to stimulants.

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7–15 years as well as the impact of EAAT on the magnitude of stress in the parent–child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p ≤ 0.01) as well as a progressive improvement in the child’s abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples.

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

Children and adolescents with Tourette syndrome may suffer from comorbid psychological and behavioral difficulties, primarily Attention-Deficit Hyperactivity Disorder-related manifestations including impulsive, aggressive, and disruptive behavior, and Obsessive-Compulsive Disorder-related disturbances. Often, such additional problems represent the major cause of disability, requiring their prioritization above the tic symptomatology. Here, we present six cases of children and adolescents with treatment-resistant Tourette syndrome aged 11–17 years, whose symptoms, especially the non-tic symptoms such as aggressive behavior and obsessive symptoms, failed to respond adequately to at least two different antipsychotics and, where deemed appropriate, to a combination with a medication with a different therapeutic indication or chemical class (e.g., antidepressant or anticonvulsant). Such symptomatic manifestations were significantly reduced by the time of the subsequent control visit planned 30 days later, by using lurasidone as an add-on therapy to risperidone or aripiprazole (all p ≤ 0.009). No significant neuromotor or metabolic side effects were reported in all cases in a follow-up period ranging from 4 months to 6 months, supporting the stability of the observed clinical improvement. While still investigational, the preliminary evidence presented here gives reason to hope that lurasidone could possibly be an effective option in Tourette syndrome, warranting further investigation of its potential benefits in neurodevelopmental conditions.

Possibly orally transmitted from before circa 2000 B [...]

Background and objectives: Adolescence represents a critical period for rapid psychophysical and socio-cognitive changes, with implications for health and wellbeing in later life. From this perspective, the manifestation of unhealthy lifestyles and dysfunctional behaviors may reflect a change in wellbeing requiring alertness and prompt intervention. This study investigated lifestyle behaviors and coping strategies among Italian adolescents, also in relation to the ongoing COVID-19 pandemic, and whether they would predict a change in subjective wellbeing. Materials and Methods: In the period between 1 April and 10 April 2020, adolescents aged 15–21 filled out an online survey consisting of 33 questions investigating socio-demographic characteristics, lifestyle behaviors, coping strategies, and subjective wellbeing. Results: Data was available on 306 participants. Most adolescents planned their daily routine (57.8%), engaging in structured activities (17.6–67.3%) and developing new interests (54.6%), and gave a positive reading of the ongoing period (57.8%), thus revealing adaptive coping strategies. Family wise, even though it was hard to stay at home (66%) and difficulties emerged, including self-isolation (50.7%) and quarrels (31.7%), a relevant proportion of adolescents shared their feelings (40.5%) and revaluated their family relationships (29.4–39.7%). In terms of social and school engagement, almost all adolescents kept contacts with their partner, friends, and teachers (90.2–93.5%). School commitments at home were sufficiently preserved (63.1%), however adolescents expressed preoccupations about their educational path (56.2%). A change in subjective wellbeing (49.3%) and symptoms of anxiety (39.9%) were frequently reported. A number of factors predicted a change in subjective wellbeing, including adaptive coping strategies (physical activity, OR = 2.609, 95% confidence interval (CI) 1.297–5.247; engaging in different activities than before, OR = 2.212, 95% CI 1.157–4.230), family issues (finding hard to stay at home, OR = 3.852, 95% CI 1.953–7.599; having quarrels, OR = 2.158, 95% CI 1.122–4.150), school-related behaviors (fearing a negative educational outcome, OR = 1.971, 95% 1.063–3.655), and female gender (OR = 3.647, 95% CI 1.694–7.851). Conclusions: Both personal and environmental coping resources are relevant to subjective wellbeing in adolescence and should be taken into account for prevention and early intervention in youth mental health.

Motor abnormalities have been suggested to play a role in most neuropsychiatric disorders, as a potential generic neurodevelopmental vulnerability. However, they still represent a neglected area, with a paucity of empirical studies, especially in pediatric populations. This case-control study aimed to comprehensively assess motor functioning in children with atypical neurodevelopment and investigate whether any socio-demographic or clinical characteristics would concur with motor difficulties to distinguish children with neurodevelopmental disorders (NDD) from healthy controls. Socio-demographic (age and gender) and clinical (intelligence quotient, gait, movement, and coordination) data were collected on 114 children aged 5–15 (83 with NDD, 31 healthy controls). Male children were at significantly higher risk for NDD (OR: 13.023, p < 0.001). Furthermore, there was a statistically significant interaction between the total intelligence quotient and overall coordination such that increasing levels of total intelligence quotient appeared to protect against the likelihood of being diagnosed with an NDD, but only in the context of a preserved coordination (OR: 0.964, p = 0.038). Collectively, results may have important public health implications, as they point towards the development of new approaches to establish an early prognosis in neurodevelopment, including assessing motor difficulties and mitigating their impact on children’s quality of life.

The 2019 coronavirus disease (COVID-19) outbreak could result in higher levels of psychological distress, especially among people suffering from pre-existing mental health conditions. Young individuals with autism spectrum disorders (ASD) are particularly at risk due to their vulnerability to unpredictable and complex changes. This study aimed to investigate the impact of the COVID-19 pandemic on ASD individuals, whether any pre-pandemic sociodemographic or clinical characteristics would predict a negative outcome, and to narratively characterize their needs. Parents and guardians of ASD individuals filled out an online survey consisting of 40 questions investigating socio-demographic and clinical characteristics of their children, impact of the COVID-19 outbreak on their wellbeing and needs to deal with the emergency. Data were available on 527 survey participants. The COVID-19 emergency resulted in a challenging period for 93.9% of families, increased difficulties in managing daily activities, especially free time (78.1%) and structured activities (75.7%), and, respectively, 35.5% and 41.5% of children presenting with more intense and more frequent behavior problems. Behavior problems predating the COVID-19 outbreak predicted a higher risk of more intense (odds ratio (OR) = 2.16, 95% confidence interval (CI) 1.42–3.29) and more frequent (OR = 1.67, 95% CI 1.13–2.48) disruptive behavior. Even though ASD children were receiving different types of support, also requiring specialist (19.1%) or emergency (1.5%) interventions in a relatively low proportion of cases, a number of needs emerged, including receiving more healthcare support (47.4%), especially in-home support (29.9%), as well as interventions to tackle a potentially disruptive quarantine (16.8%). The COVID-19 outbreak has undoubtedly resulted in increased difficulties among ASD individuals.

Several studies have advanced the understanding of the effects of cannabis on cognitive function. A comprehensive reappraisal of such literature may help in drawing conclusions about the potential risks associated with cannabis use. In summary, the evidence suggests that earlier age of use, high-frequency and high-potency cannabis use, as well as sustained use over time and use of synthetic cannabinoids, are all correlated with a higher likelihood of developing potentially severe and persistent executive function impairments. While the exact mechanisms underlying the adverse effects of cannabis on cognition are not completely clear, Magnetic Resonance Imaging (MRI) studies support the presence of both structural and functional alterations associated with cannabis use. Cognitive dysfunction is also a core feature of many neuropsychiatric disorders and care must be taken regarding the effects of cannabis use in these patient populations. Cognitive impairments affect patients’ daily functions, sociability, and long-term outcome, posing elevated economic, social, and clinical burdens. There is, thus, a compelling case for implementing behavioral and cognitive rehabilitation therapies for these patients, as well as investigating the endocannabinoid system in the development of new psychopharmacological treatments.

Background: Cannabis use can increase the risk of psychosis, and the acute administration of its key psychoactive ingredient, delta-9-tetrahydrocannabinol (∆9-THC), can induce transient psychotomimetic symptoms. Methods: A double-blind, randomized, placebo-controlled crossover design was used to investigate the symptomatic effects of acute intravenous administration of ∆9-THC (1.19 mg/2 mL) in 16 healthy participants (seven males) with modest previous cannabis exposure. Results: In the 20 min following acute ∆9-THC administration, symptomatic effects of at least mild severity were present in 94% of the cohort, with moderate to severe symptoms having a much lower prevalence (19%). Nearly one-third (31%) of the volunteers were still experiencing protracted mild symptomatic effects 2.5 h after exposure to ∆9-THC. Compared to the Δ9-THC challenge, most of the study participants did not experience any symptomatic effects following placebo administration (62%). Acute physical reactions were 2.5 times more frequent after Δ9-THC (31%) than placebo (12%). Male and female participants differed in terms of acute Δ9-THC effects, with some negative symptoms occurring more frequently in female (56% to 89%) than male participants (0% to 29%), and acute physical reactions occurring exclusively in the female gender (56%). Conclusions: These results have implications for future research, also in light of cannabis being the most widely used illicit drug.