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A new postmodern depression type, named "Modern-Type Depression" (MTD), is emerging in Western countries. MTD is often underdiagnosed, mainly due to potentially higher comorbidity with technology-based addictions, including Internet Gaming Disorder (IGD). However, the definition of the relationship between MTD and IGD is still controversial, as few data have been published thus far. In particular, there are no data specifically investigating the prevalence of MTD within Italian young subjects with IGD, as well as their mutual association. Hence, within the SWATCH (Social Withdrawal and TeCno-mediated mental Health issues) project, our study aimed to identify the prevalence of MTD in a sample of Italian young adults who play video games by providing a clinical characterization of MTD within a group of IGD individuals (IGD+) versus a group without IGD (IGD-) who play video games. Our cross-sectional case-control study recruited a sample of 543 Italian young video-gaming players (aged 18-35) from the larger SWATCH database, stratified as IGD+ versus IGD-. Subjects were administered the 22-item Tarumi's Modern-Type Depression Trait Scale (TACS-22), the Motives for Online Gaming Questionnaire (MOGQ), and the Internet Gaming Disorder Scale-Short Form (IGDS9-SF). Around 21.7% of the total sample was represented by MTD individuals, while within the IGD sample, around 34% of subjects had MTD. Within the MTD group, significantly higher scores at IGDS-9SF ( p < 0.001), MOGQ "Escape from reality" ( p < 0.001), "Fantasy" ( p < 0.001), and MOGQ total score ( p = 0.003) were found compared to MTD-. According to the multivariate regression model, controlled for sex and age, higher scores in the TACS-22 were positively predicted by the total score of IGDS9-SF ( p = 0.003), the MOGQ "Escape from Reality" subscale ( p = 0.014), and MOGQ "Fantasy" ( p = 0.011), and negatively predicted by the MOGQ "Competition" subscale ( p = 0.035) [F (4538) = 17.265; p < 0.001]. Our findings suggested that MTD displays a strong association with IGD. Video-gaming players who do not have IGD appear to be less prone to MTD; this suggests that further studies could be carried out to specifically investigate whether pathological use of video games could also be determined by the presence of MTD.

Lumateperone (also known as ITI-007 or ITI-722) represents a novel second-generation medication characterized by a favorable safety and tolerability profile. This is attributed to its notable selectivity for D2 receptors within specific regions of the brain. The U.S. Food and Drug Administration (FDA) granted approval for the treatment of schizophrenia in adults in December 2019. Additionally, it gained approval for addressing depressive episodes associated with bipolar I and II disorders in adults, either as a standalone therapy or in conjunction with lithium or valproate, in December 2021. The objective of this investigation is to systematically review the existing literature to assess the safety, tolerability, and efficacy of lumateperone in the treatment of schizophrenia. Lumateperone has demonstrated effectiveness in addressing positive, negative, and cognitive symptoms associated with schizophrenia. The evaluation of safety indicators in the reviewed studies indicates that lumateperone is deemed to be a well-tolerated and safe antipsychotic. Additional research is warranted to explore lumateperone's efficacy in managing major depressive disorders, behavioral issues in Alzheimer's disease and dementia, sleep maintenance insomnia, bipolar disorders, and personality disorders.

Selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of psychopharmacology. However, they cause side effects such as sexual dysfunction, leading to the discontinuation of treatment. We aimed to investigate the efficacy and safety of drug holidays for women experiencing sexual dysfunction Induced by SSRIs other than fluoxetine. This study was an 8-week randomized, open-label, controlled trial including married women aged between 18 and 50 years who had experienced sexual dysfunction while undergoing treatment with SSRIs. The intervention group implemented drug holidays by not taking medications on Thursdays and Fridays, while the control group continued regular medication use. The female sexual function index (FSFI) and the 28-question general health questionnaire (GHQ-28) were administered to assess sexual function and mental health, respectively. A total of 50 participants completed the trial. The drug holidays' group showed significant improvements in arousal ( p < 0.001), desire ( p = 0.001), orgasm ( p < 0.001), satisfaction ( p < 0.001), lubrication ( p = 0.021), and overall sexual health ( p < 0.001). The between-group difference of pain was significant ( p < 0.001), despite no significant within-group change. Mental health improved in both groups, despite no significant between-group difference. No major adverse effects were reported. Drug holidays did not introduce immediate safety concerns or significant adverse effects during the timeframe of eight weeks, suggesting that it may be a safe and effective strategy for managing SSRI-induced sexual dysfunction in women, alongside improving mental health. Further research is needed to reach a definitive conclusion.

In recent years, there has been a gradual digitalization of our society, resulting in intensified technology use for daily life activities, including the emergence of problematic Internet use (PIU). Few studies specifically addressed the boredom and loneliness dimensions in mediating the association between depression, anxiety, and stress levels and the onset of PIU. A nationwide population-based cross-sectional case-control study was carried out by recruiting a sample of Italian young people (aged 18-35). Only 1643 participants were selected for the analyses based on the age and the presence versus absence of PIU. Participants were mainly females (68.7%), with a mean age of 21.8 (SD = 1.7). Non-PIU individuals had significantly stable relationships ( p = 0.012), siblings ( p = 0.044) and lived with their family ( p = 0.010), compared to PIU. PIU individuals displayed significantly higher depression, anxiety, and stress, as well as higher loneliness and boredom levels (all p < 0.001), compared to non-PIU. Depressive symptomatology predicted PIU and that their interaction is positively double mediated by boredom and loneliness (ß = 0.3829 (0.0245), 95%CI = 0.3349-0.4309). Our findings suggested that boredom and loneliness dimensions could act as mediators in the association between depressive symptomatology and the likelihood of PIU onset and maintenance.

Background and Objectives : Now more than ever, there is an obvious need to reduce the overall burden of disease and risk of premature mortality that are associated with mental health and substance use disorders among young people. However, the current state of research and evidence-based clinical care for high-risk substance use among youth is fragmented and scarce. The objective of the study is to establish consensus for the prevention, treatment, and management of high-risk substance use and overdose among youth (10 to 24 years old). Materials and Methods : A modified Delphi technique was used based on the combination of scientific evidence and clinical experience of a group of 31 experts representing 10 countries. A semi-structured questionnaire with five domains (clinical risks, target populations, intervention goals, intervention strategies, and settings/expertise) was shared with the panelists. Based on their responses, statements were developed, which were subsequently revised and finalized through three iterations of feedback. Results: Among the five major domains, 60 statements reached consensus. Importantly, experts agreed that screening in primary care and other clinical settings is recommended for all youth, and that the objectives of treating youth with high-risk substance use are to reduce harm and mortality while promoting resilience and healthy development. For all substance use disorders, evidence-based interventions should be available and should be used according to the needs and preferences of the patient. Involuntary admission was the only topic that did not reach consensus, mainly due to its ethical implications and resulting lack of comparable evidence. Conclusions: High-risk substance use and overdoses among youth have become a major challenge. The system's response has been insufficient and needs substantial change. Internationally devised consensus statements provide a first step in system improvement and reform.

The etiopathogenesis of depression is not entirely understood. Several studies have investigated the role of inflammation in major depressive disorder. The present work aims to review the literature on the association between C-Reactive Protein (CRP) and depression. A systematic review was performed for the topics of 'CRP' and 'depression' using the PubMed database from inception to December 2021. Fifty-six studies were identified and included in the review. Evidence suggested the presence of dysregulation in the inflammation system in individuals with depression. In most studies, higher blood CRP levels were associated with greater symptom severity, a specific pattern of depressive symptoms, and a worse response to treatment. Moreover, about one-third of depressed patients showed a low-grade inflammatory state, suggesting the presence of a different major depressive disorder (MDD) subgroup with a distinct etiopathogenesis, clinical course, treatment response, and prognosis, which could benefit from monitoring of CRP levels and might potentially respond to anti-inflammatory treatments. This work provides robust evidence about the potential role of CRP and its blood levels in depressive disorders. These findings can be relevant to developing new therapeutic strategies and better understanding if CRP may be considered a valuable biomarker for depression.

COVID-19 pandemic and its related containment measures have been associated with increased levels of stress, anxiety and depression in the general population. While the use of digital media has been greatly promoted by national governments and international authorities to maintain social contacts and healthy lifestyle behaviors, its increased access may also bear the risk of inappropriate or excessive use of internet-related resources. The present study, part of the COVID Mental hEalth Trial (COMET) study, aims at investigating the possible relationship between social isolation, the use of digital resources and the development of their problematic use. A cross sectional survey was carried out to explore the prevalence of internet addiction, excessive use of social media, problematic video gaming and binge watching, during Italian phase II (May-June 2020) and III (June-September 2020) of the pandemic in 1385 individuals (62.5% female, mean age 32.5 ± 12.9) mainly living in Central Italy (52.4%). Data were stratified according to phase II/III and three groups of Italian regions (northern, central and southern). Compared to the larger COMET study, most participants exhibited significant higher levels of severe-to-extremely-severe depressive symptoms (46.3% vs. 12.4%; p < 0.01) and extremely severe anxiety symptoms (77.8% vs. 7.5%; p < 0.01). We also observed a rise in problematic internet use and excessive gaming over time. Mediation analyses revealed that COVID-19-related general psychopathology, stress, anxiety, depression and social isolation play a significant role in the emergence of problematic internet use, social media addiction and problematic video gaming. Professional gamers and younger subjects emerged as sub-populations particularly at risk of developing digital addictions. If confirmed in larger and more homogenous samples, our findings may help in shedding light on possible preventive and treatment strategies for digital addictions.

Background and Objectives : The Internet is widely used and disseminated amongst youngsters and many web-based applications may serve to improve mental health care access, particularly in remote and distant sites or in settings where there is a shortage of mental health practitioners. However, in recent years, specific digital psychiatry interventions have been developed and implemented for special populations such as children and adolescents. Materials and Methods : Hereby, we describe the current state-of-the-art in the field of TMH application for young mental health, focusing on recent studies concerning anxiety, obsessive-compulsive disorder and affective disorders. Results: After screening and selection process, a total of 56 studies focusing on TMH applied to youth depression ( n = 29), to only youth anxiety ( n = 12) or mixed youth anxiety/depression ( n = 7) and youth OCD ( n = 8) were selected and retrieved. Conclusions: Telemental Health (TMH; i.e., the use of telecommunications and information technology to provide access to mental health assessment, diagnosis, intervention, consultation, supervision across distance) may offer an effective and efficacious tool to overcome many of the barriers encountering in the delivery of young mental health care.

Background and Objectives : Over the past twenty years a large number of new psychoactive substances (NPS) have entered and modified the recreational drug scene. Their intake has been associated with health-related risks, especially so for vulnerable populations such as people with severe mental illness, who might be at higher risk of suicidality or self-injurious behavior. This paper aims at providing an overview of NPS abuse and the effects on mental health and suicidality issues, by performing a literature review of the current related knowledge, thereby identifying those substances that, more than others, are linked to suicidal behaviors. Materials and Methods : A comprehensive and updated overview of the literature regarding suicidality and NPS categories has been undertaken. An electronic search was performed, including all papers published up to March 2021, using the following keywords "NPS" OR "new psychoactive substances" OR "novel psychoactive substances" OR "synthetic cannabinoids" OR "phenethylamines" OR "synthetic cathinones" OR "tryptamines" OR "piperazines" OR "new synthetic opioids" OR "designer benzodiazepines" AND ("suicide" OR "suicidality") NOT review NOT animal on the PubMed, Cochrane Library, and Web of Science online databases. Results : Suicidality and self-injurious behavior appear to be frequently associated with some NPS such as cathinones, synthetic cannabinoids, and new synthetic opioids. The results are organized according to the substances recorded. Conclusion : The growing use of NPS has become a significant clinical issue, causing increasing concern and challenges for clinicians working in both mental health and emergency departments. Thus, considering the associations between NPS and suicidality or self-injurious behaviors, areas where suicide-prevention efforts and strategies might be focused are the early detection, monitoring, and restriction of NPS.

Attention deficit hyperactivity disorder (ADHD) is a condition that usually has its onset in childhood. Although the disorder persists into adulthood in half of cases, adult ADHD is often not recognized due to different psychopathological characteristics, quite often overlapping with other diagnoses such as mood, anxiety and personality disorders. This is especially true for bipolar disorder (BD), which shares several symptoms with adult ADHD. Moreover, besides an overlapping clinical presentation, BD is often co-occurring in adults with ADHD, with comorbidity figures as high as 20%. This review will focus on the comorbidity between ADHD and BD by exploring the magnitude of the phenomenon and evaluating the clinical and functional characteristics associated with ADHD-BD comorbidity in adults. Finally, the review will address the implications of pharmacologically treating the ADHD-BD comorbidity, providing suggestions in how to treat these complex patients and addressing the issue of treatment-induced manic switch with the use of stimulants and other medications for ADHD.

Bipolar disorder (BD) is a complex neurobiological disorder characterized by a pathologic mood swing. Digital phenotyping, defined as the 'moment-by-moment quantification of the individual-level human phenotype in its own environment', represents a new approach aimed at measuring the human behavior and may theoretically enhance clinicians' capability in early identification, diagnosis, and management of any mental health conditions, including BD. Moreover, a digital phenotyping approach may easily introduce and allow clinicians to perform a more personalized and patient-tailored diagnostic and therapeutic approach, in line with the framework of precision psychiatry. The aim of the present paper is to investigate the role of digital phenotyping in BD. Despite scarce literature published so far, extremely heterogeneous methodological strategies, and limitations, digital phenotyping may represent a grounding research and clinical field in BD, by owning the potentialities to quickly identify, diagnose, longitudinally monitor, and evaluating clinical response and remission to psychotropic drugs. Finally, digital phenotyping might potentially constitute a possible predictive marker for mood disorders.

Background and Objectives: Post-traumatic stress disorder (PTSD) is a common psychiatric disorder resulting from a traumatic event, is manifested through hyperarousal, anxiety, depressive symptoms, and sleep disturbances. Despite several therapeutic approaches being available, both pharmacological and psychological, recently a growing interest has developed in using cannabis and synthetic cannabinoids stems from their consideration as more efficient and better tolerated alternatives for the treatment of this condition. The present paper aims to evaluate the clinical and therapeutic potentials of medical cannabis and synthetic cannabinoids in treating PTSD patients., Methods: A systematic electronic search was performed, including all papers published up to May 2019, using the following keywords (((cannabis[Title/Abstract]) OR (synthetic cannabinoids [Title/Abstract])) AND ((PTSD[Title/Abstract]) OR (Posttraumatic stress disorder[Title/Abstract]))) for the topics 'Cannabis', 'Synthetic Cannabinoids', 'PTSD', and MESH terms, on the PubMed, Cochrane Library, and Web of Science online databases. For data gathering purposes, PRISMA guidelines were followed. Results were organized into two groups, considering cannabis and synthetic cannabinoids as different therapeutic approaches for PTSD., Results: Present data show that cannabis and synthetic cannabinoids, both acting on the endocannabinoids system, may have a potential therapeutic use for improving PTSD symptoms, e.g., reducing anxiety, modulating memory-related processes, and improving sleep., Conclusions: Even though the current literature suggests that cannabis and synthetic cannabinoids may have a role in the treatment of PTSD, there is currently limited evidence regarding their safety and efficacy. Therefore, additional research is needed in order to better understand the effectiveness and therapeutic usage of these drug classes and monitor their safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Despite the continuous advancement in neurosciences as well as in the knowledge of human behaviors pathophysiology, currently suicide represents a puzzling challenge. The World Health Organization (WHO) has established that one million people die by suicide every year, with the impressive daily rate of a suicide every 40 s. The weightiest concern about suicidal behavior is how difficult it is for healthcare professionals to predict. However, recent evidence in genomic studies has pointed out the essential role that genetics could play in influencing person's suicide risk. Combining genomic and clinical risk assessment approaches, some studies have identified a number of biomarkers for suicidal ideation, which are involved in neural connectivity, neural activity, mood, as well as in immune and inflammatory response, such as the mammalian target of rapamycin (mTOR) signaling. This interesting discovery provides the neurobiological bases for the use of drugs that impact these specific signaling pathways in the treatment of suicidality, such as ketamine. Ketamine, an N -methyl-d-aspartate glutamate (NMDA) antagonist agent, has recently hit the headlines because of its rapid antidepressant and concurrent anti-suicidal action. Here we review the preclinical and clinical evidence that lay the foundations of the efficacy of ketamine in the treatment of suicidal ideation in mood disorders, thereby also approaching the essential question of the understanding of neurobiological processes of suicide and the potential therapeutics.

Loxapine is a first generation antipsychotic, belonging to the dibenzoxazepine class. Recently, loxapine has been reformulated at a lower dose, producing an inhaled powder that can be directly administered to the lungs to treat the agitation associated with psychiatric disorders, such as schizophrenia and bipolar disorder. Thus, the aim of this narrative and clinical mini-review was to evaluate the efficacy and tolerability of inhaled loxapine in the treatment of acute agitation in patients with psychiatric disorders. The efficacy of inhaled loxapine has been evaluated in one Phase II trial on patients with schizophrenia, and in two Phase III trials in patients with schizophrenia and bipolar disorder. Moreover, there are two published case series on patients with borderline personality disorder and dual diagnosis patients. Inhaled loxapine has proven to be effective and generally well tolerated when administered to agitated patients with schizophrenia and bipolar disorder. Two case series have suggested that inhaled loxapine may also be useful to treat agitation in patients with borderline personality disorder and with dual diagnosis, but further studies are needed to clarify this point. However, the administration of inhaled loxapine requires at least some kind of patient collaboration, and is not recommended in the treatment of severe agitation in totally uncooperative patients. Moreover, the drug-related risk of bronchospasm must always be kept in mind when planning to use inhaled loxapine, leading to a careful patient assessment prior to, and after, administration. Also, the higher costs of inhaled loxapine, when compared to oral and intramuscular medications, should be taken into account when selecting it for the treatment of agitation.

Dopamine-glutamate interplay dysfunctions have been suggested as pathophysiological key determinants of major psychotic disorders, above all schizophrenia and mood disorders. For the most part, synaptic interactions between dopamine and glutamate signaling pathways take part in the postsynaptic density, a specialized ultrastructure localized under the membrane of glutamatergic excitatory synapses. Multiple proteins, with the role of adaptors, regulators, effectors, and scaffolds compose the postsynaptic density network. They form structural and functional crossroads where multiple signals, starting at membrane receptors, are received, elaborated, integrated, and routed to appropriate nuclear targets. Moreover, transductional pathways belonging to different receptors may be functionally interconnected through postsynaptic density molecules. Several studies have demonstrated that psychopharmacologic drugs may differentially affect the expression and function of postsynaptic genes and proteins, depending upon the peculiar receptor profile of each compound. Thus, through postsynaptic network modulation, these drugs may induce dopamine-glutamate synaptic remodeling, which is at the basis of their long-term physiologic effects. In this review, we will discuss the role of postsynaptic proteins in dopamine-glutamate signals integration, as well as the peculiar impact of different psychotropic drugs used in clinical practice on postsynaptic remodeling, thereby trying to point out the possible future molecular targets of "synapse-based" psychiatric therapeutic strategies., Competing Interests: The authors declare no conflict of interest.