Fasting insulinemia as biomarker of illness relapse in patients with severe mental illness?

Severe Mental Illness (SMI) is often associated with metabolic alteration and/or metabolic syndrome, which may determine an increased mortality due to a further increased cardiovascular risk. The relationship with metabolic syndrome is often bidirectional, resulting in a pathoplastic effect of these dysmetabolisms. Among the several hormones involved, insulin appears to play a key role, albeit not entirely clear. The aim of our real-world cross-sectional observational study is to investigate a set of metabolic biomarkers of illness relapse/recurrence/onset in a cohort of 310 adult SMI inpatients consecutively admitted to the Psychiatry Clinic of the Azienda Ospedaliero Universitaria of Marche, in Ancona (Italy), between February 2021 and February 2024. According to the stepwise multivariate regression model, a higher number of acute episodes per year was positively predicted by the age of illness onset, the lifetime number of suicidal attempts and fasting insulinemia and negatively by the participant's age. A second stepwise multivariate regression model using only the metabolic characteristics as independent variables, found that a higher number of acute episodes per year was predicted positively by the fasting insulinemia and red blood cells and negatively by the abdominal circumference. Overall, our findings could provide practical implications for the treatment and management of SMI patients, emphasizing the importance of monitoring and managing metabolic factors, particularly insulinemia, metabolic syndrome and insulin resistance. Finally, insulinemia could potentially act as metabolic biomarker of illness relapse, though more larger and longitudinal studies should be carried out to confirm these results.

Cyclothymic affective temperament and low positive attitude coping strategies as predictors of comorbid depressive symptomatology in adult ADHD patients.

INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) in adults could be frequently underdiagnosed due to concomitant psychiatric disorders, including depressive symptomatology, which could determine inappropriate treatments. Our study aims at clinically characterizing adult ADHD with or without depressive symptomatology in order to identify the relationship with specific affective temperamental profiles and coping strategies. METHODS: A total of 225 outpatients consecutively afferent to our outpatient adult ADHD service since September 2019 were retrospectively screened for eligibility and administered Beck Depression Inventory-II (BDI-II), Coping Orientation to Problems Experienced Inventory (COPE-NV) and Temperament Evaluation of the Memphis, Pisa, Paris and San Diego (TEMPS-M). RESULTS: 64.7 % of patients displayed a significant comorbid depressive symptomatology. According to the multivariate linear regression model, depressive levels were positively predicted by TEMPS-M cyclothymic subscale (B = 0.567, p = 0.004) and negatively predicted by COPE-NVI "positive attitude" subscale (B = -0.438, p = 0.024) (R = 0.496, R2 = 0.246, F(2,66) = 10.747, p < 0.001). LIMITATION: While considering the results, it should be taken in consideration that: the assessment was carried out only at baseline, our sample is constituted only by adult ADHD patients and mostly without a previous ADHD diagnosis, the presence of a discrepancy between the rates of ADHD subtypes, the absence of a healthy control group and emotional dysregulation was not directly assessed. CONCLUSION: Affective temperamental profiles and coping strategies could help in clinically characterizing and personalizing treatment in adult comorbid ADHD-depressive symptomatology patients. Further research is warranted to explore the efficacy of targeted psychotherapeutic and pharmacological interventions within this ADHD sub-sample.

The role of Theory of Mind in the transition towards suicidal attempts in youth NSSI: an exploratory pilot study.

Non-suicidal self-injury (NSSI) can both precede and co-occur with suicidal attempts (SA). Underlying mechanisms/factors leading to the transition to SA in NSSI youths have been proposed (including the role of social cognition), despite they should be yet confirmed. Therefore, the study aims at exploring the role of the Theory of Mind in the differentiation of a sample of NSSI youngsters (aged 15-24) according to the presence of SA. We divided the sample into 4 groups using the Deliberate Self Harm Inventory (DSHI) and Columbia Suicide Severity Rating Scale (C-SSRS): control group (notNSSInotSA), NSSI without SA (NSSInotSA), NSSI with SA (NSSIplusSA), and SA without NSSI (SAonly). NSSIplusSA patients displayed higher Reading the Mind in the Eyes Test (RMET) scores (indicative of ToM abilities) than both the NSSInotSA (p=0.0016) and SAonly groups (p=0.0198), while SAonly patients showed lower RMET scores compared to the control group (p=0.0214). Multiple regression models used to differentiate NSSInotSA and NSSIplusSA found a significant association between RMET and LOSCS-CSC (Level Of Self-Criticism Scale-Comparative Self-Criticism) (pC=0.0802, pD=0.0016, pG=0.0053). Our findings supported the hypothesis that a hypertrophic affective ToM may possibly be associated with the occurrence of SA in youth NSSI. Further larger and longitudinal studies should confirm these preliminary findings, by exploring all social cognition dimensions.

"Swipe & slice": decoding digital struggles with non-suicidal self-injuries among youngsters.

Introduction: Nonsuicidal-self-injury (NSSI)-related content recently emerged on social networking sites (SNS), despite its relationship with NSSI conducts is still unclear. Methods: Hence, the current population-based cross-sectional study investigated the interplay between SNS use, NSSI content engagement, risky social media challenges (RSMCs), in a sample of 404 young adults (aged 18-24), focusing on the influence of problematic social media use (PSMU) and fear of missing out (FoMO). Results: Around 51.5% of the samplewas engaged inNSSI-related contents on SNS, being mostly females (p<0.001), younger (p=0.005), transgender people and nonbinary people (p=0.030) and those who displayed higher PSMU (p<0.001) or FoMO (p=0.031). Around 66.2% of the sample currently practice NSSIs, predominantly among females (p<0.001), those using BeReal (p=0.012), actively looking for NSSIrelated contents on SNS (p<0.001) to be part of a group (p=0.0025) or learn how to practice NSSI (p=0.025). PSMU (p<0.001) and FoMO (p<0.001) emerged as significant predictors of NSSI content engagement, particularly among active seekers. NSSI conducts were significantly predicted by FoMO (p<0.001) and Snapchat (p=0.044), while negatively predicted by male sex (p<0.001), higher educational level (p=0.019) and age at which NSSI-related contents were firstly looked for (p=0.028). Discussion: These findings underline the need to implement preventivepolicies and targeted interventions to monitor NSSI-related contents on SNS, the impact of PSMU and FoMO on NSSI, particularly among youngsters.

The Role of Lurasidone in Managing Depressive Symptoms in People with Schizophrenia: A Review.

BACKGROUND: Schizophrenia is a severe mental disorder characterized by positive, negative, affective, and cognitive symptoms. Affective symptoms in patients with schizophrenia have traditionally been overlooked or even neglected because they are not considered as fundamental as positive and negative symptoms in the choice of medication. METHODS: This paper aims to systematically evaluate the efficacy and safety of lurasidone in the treatment of depressive symptoms of schizophrenia. RESULTS: Lurasidone appears to be particularly effective on the depressive symptomatology of schizophrenia while also alleviating the positive and negative symptoms associated with the illness. CONCLUSIONS: The efficacy of lurasidone in treating patients with first-episode psychosis who present with predominant depressive symptoms suggests that this medication may be a valuable treatment option not only for established cases of schizophrenia but also for individuals in the early stages of the illness. The good tolerability of lurasidone is an important factor that may positively influence treatment decisions.

A case report of LAI two injection start in a 16-year-old adolescent with severe manic episode and comorbid cannabinoid use disorder.

There is a lack of randomized clinical trials and few studies regarding long-acting injectable antipsychotics (LAIs) in adolescents. Non-adherence, aggressiveness, comorbid substance use disorder and lack of insight may represent the main reasons for starting LAIs. Hereby we describe a 16-year-old male adolescent subject with bipolar type I disorder and comorbid cannabinoid use disorder, successfully treated with two-injection start regimen of LAI aripiprazole. Two-injection start regime of aripiprazole could represent an effective and safe therapeutic option for adolescents with early onset bipolar disorder.

Predominant affective temperaments in depressive patients with severe social withdrawal.

BACKGROUND: Hikikomori (HK) is characterized by self-isolation and social refusal, being more likely also associated with affective disorders, including depression. This case-control study primarily aimed at identifying (if any) predominant affective temperaments are associated with HK in depressed versus not-depressed individuals. Secondary objectives comprise assessing which other psychopathological dimensions (e.g., boredom, anxiety) are associated with the HK specifier in depressed individuals. METHODS: From the larger SWATCH study, 687 Italian young people were screened for depression, as measured by 9 items-Patient Health Questionnaire (PHQ-9) and HK-like social withdrawal, through the Hikikomori Questionnaire-25 (HQ-25). All subjects were administered a brief-Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-M), the 7 items-Generalized Anxiety Disorder (GAD-7) and the Multidimensional State Boredom Scale (MSBS). RESULTS: Males reported significantly higher scores at HQ-25 total score than females (p = 0.026). In the total sample, HK social withdrawal is positively predicted by MSBS low arousal, disengagement, depressive levels, depressive and irritable affective temperaments, while negatively by anxiety (F(6, 680) = 82.336, p < 0.001, R2 = 0.421). By selecting only depressed sample, HQ-25 is positively predicted by MSBS total score, low arousal and depressive affective temperament, while negatively by MSBS high arousal (F(4, 383) = 48.544, p < 0.001, R2 = 0.336). The logistic regression model found that the likelihood of developing depression with the HK specifier is significantly predicted by depressive and cyclothymic affective temperaments. CONCLUSIONS: These preliminary findings could help in clinically characterizing the relationship between specific affective temperamental profiles among individuals with depression with/without HK specifier, in order to provide a more tailored and personalized therapeutic approach. Our Italian study should be extensively replicated in larger, longitudinal and multicentric pan-European studies, by specifically assessing the impact of these findings on depression clinical course, prognosis and treatment outcomes.

The interplay between mentalization, personality traits and burnout in psychiatry training: Results from a large multicenter controlled study.

BACKGROUND: A better characterization of educational processes during psychiatry training is needed, both to foster personal resilience and occupational proficiency. METHODS: An adequate coverage of medical residents at the national level was reached (41.86% of the total reference population, 29 out of 36 training centers-80.55%). Controls were recruited among residents in other medical specialties. All participants were assessed by questionnaires to evaluate early life experiences, attachment style, personality traits, coping strategies, emotional competencies. A Structural Equation Model (SEM) framework was employed to investigate the interplay between individual factors. RESULTS: A total sample of 936 people was recruited (87.9% response-rate; 645 residents in psychiatry, 291 other medical residents). Psychiatry trainees reported a higher prevalence of adverse childhood experiences (emotional abuse, emotional neglect, physical neglect), greater attachment insecurity (anxious or avoidant) in comparison to other medical trainees. Psychiatry residents also reported higher social support-seeking as a coping strategy, lower problem-orientation, and lower transcendence. Lower neuroticism, higher openness to experience, and higher emotional awareness were also observed in psychiatry trainees. Psychiatry training was associated with a redefinition of conflict management skills as a function of seniority. The SEM model provided support for an interplay between early traumatic experiences, mentalization skills (coping strategies, emotion regulation), interpersonal competencies and occupational distress. CONCLUSIONS: The findings of the present study supported a theoretical model based on mentalization theory for the interactions between personal and relational competencies in psychiatry training, thus providing potential target of remodulation and redefinition of this specific process of education.

An expert opinion on the pharmacological interventions for Disruptive Mood Dysregulation Disorder (DMDD).

INTRODUCTION: Disruptive Mood Dysregulation Disorder (DMDD) was officially introduced as a new diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5), under the category of depressive disorders. AREAS COVERED: A comprehensive overview and a critical commentary on the currently investigated psychopharmacological approaches for the treatment of DMDD have been here provided. EXPERT OPINION: Behavioral and psychosocial interventions should be considered as first-line treatment strategies. When ineffective or partially effective, psychopharmacological strategy is recommended. Overall, pharmacological strategy should be preferred in those individuals with psychiatric comorbidities (e.g. ADHD). Indeed, so far published studies on pharmacological strategies in DMDD are scant and heterogeneous (i.e. age, assessment tools, symptomatology profile, comorbidity, and so forth). Therefore, DMDD psychopharmacological guidelines are needed, particularly to guide clinicians toward the patient's typical symptom profile who could benefit from psychopharmacological strategy.

Could the Construct of Modern-Type Depression Predict Internet Gaming Disorder in Italian Video Gamers? A Case-Control Study.

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.

Lurasidone as add-on to fluoxetine in obsessive-compulsive disorder with comorbid restrictive anorexia: a case report.

Obsessive-compulsive disorder (OCD) is a pervasive disabling disorder that may overlap with other psychiatric conditions, including anorexia nervosa. Recent guidelines recommend low doses of second-generation antipsychotics as add-on therapy to selective serotonin reuptake inhibitors (SSRIs) for those patients presenting OCD who display residual symptomatology. Here we report a clinical case of a 45-years-old woman affected by severe OCD in comorbidity with anorexia nervosa, restrictive type (AN-r), treated with fluoxetine (titrated up to 40 mg/day) in augmentation with low doses of lurasidone (37 mg/day). At baseline and during a 6 months-follow-up we administered Clinical Global Impression-Severity, Symptom Checklist-90 items, Y-BOCS-II (Yale-Brown Obsessive Compulsive Scale) and EDI-3 (Eating Disorder Inventory). After 1 month of augmentation treatment, a clinically significant response was observed on obsessive symptoms at Y-BOCS-II (≥35% Y-BOCS reduction) and eating symptomatology at EDI-3. Full remission was reported after 3 months (Y-BOCS scoring ≤14) ( P  < 0.01). Further longitudinal and real-world effectiveness studies should be implemented to confirm these novel results, to investigate the potential of lurasidone as add-on strategy to SSRI in poor responder OCD patients, including treatment-resistant-OCD (tr-OCD), as well as in improving eating disorder symptomatology, whereas there is comorbidity with AN-r.

Practical application of digital therapeutics in people with mood disorders.

Digital therapeutics (DTx) offer evidence-based digitally-delivered high quality standards applications and/or softwares in the prevention, management and treatment of several medical conditions, including mood disorders. Nowadays, there are only three DTx officially approved by the Food and Drug Administration for mental conditions and there are still very few DTx developed in the context of mood disorders. The current comprehensive overview aims at providing a summary of currently published studies on DTx clinical applications in major depressive disorder (MDD), depressive symptomatology and bipolar disorder (BD), by using PubMed/MEDLINE and Scopus databases. Fifteen studies have been selected (10 on DTx in depressive symptomatology and/or MDD; 4 on BD; 1 on MDD and BD). Literature on DTx in mood disorders is still lacking, being mostly constituted by feasibility and acceptability rather than efficacy/effectiveness outcomes, particularly in BD. More studies focused on MDD compared to BD. Most DTx on MDD have been developed based on cognitive behaviour therapy interventions while on BD are based on psychoeducation. All studies assessing symptom severity improvement pre- vs. postinterventions demonstrated a significant postintervention improvement. Therefore, despite the preliminary encouraging results of studies here retrieved, their methodology is still too heterogeneous to allow comparisons and the generalizability of their findings. Further studies are warranted, in more larger samples involving multiple sites, including measures of both specific symptom effects as well as acceptability, feasibility and effectiveness in the real-world settings.

Digitalising mental health care: Practical recommendations from the European Psychiatric Association.

The digitalisation of mental health care is expected to improve the accessibility and quality of specialised treatment services and introduce innovative methods to study, assess, and monitor mental health disorders. In this narrative review and practical recommendation of the European Psychiatric Association (EPA), we aim to help healthcare providers and policymakers to navigate this rapidly evolving field. We provide an overview of the current scientific and implementation status across two major domains of digitalisation: i) digital mental health interventions and ii) digital phenotyping, discuss the potential of each domain to improve the accessibility and outcomes of mental health services, and highlight current challenges faced by researchers, clinicians, and service users. Furthermore, we make several recommendations meant to foster the widespread adoption of evidence-based digital solutions for mental health care in the member states of the EPA. To realise the vision of a digitalised, patient-centred, and data-driven mental health ecosystem, a number of implementation challenges must be considered and addressed, spanning from human, technical, ethical-legal, and economic barriers. The list of priority areas and action points our expert panel has identified could serve as a playbook for this process.

The Novel Antipsychotic Lumateperone (Iti-007) in the Treatment of Schizophrenia: A Systematic Review.

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.

Acute stress symptoms in general population during the first wave of COVID lockdown in Italy: Results from the COMET trial.

BACKGROUND: The coronavirus disease of 2019 (COVID-19) pandemic is an unprecedented traumatic event that has severely impacted social, economic, and health well-being worldwide. The COvid Mental hEalth Trial was specifically designed to evaluate the impact of the COVID-19 pandemic and its containment measures on the mental health of the Italian general population in terms of COVID-19-related acute stress disorder (ASD) symptoms. METHODS: The present cross-sectional study is based on an online survey carried out in the period March-May 2020. Italian general adult population was invited to compile an anonymous survey, which included the severity of acute stress symptoms scale/National Stressful Events Survey Short Scale to investigate the occurrence and severity of ASD symptoms. RESULTS: The final sample consisted of 20,720 participants. During the lockdown, subjects with pre-existing mental health problems reported a statistically significant higher risk of acute post-traumatic symptoms compared to the general population (B: 2.57; 95% CI:2.04-3.09; p < .0001) and health care professionals (B: .37; 95% CI: .02-0.72; p < .05). According to multivariate regression models, the levels of acute post-traumatic symptoms (p < .0001) were higher in younger and female respondents. Social isolation and sleep disorder/insomnia represented positive predictors of acute stress (B = 3.32, 95% CI = 3.08-3.57). CONCLUSIONS: Concerns about the risk of infection as well as social isolation caused a higher incidence of acute post-traumatic stress symptoms that may predict the subsequent development of post-traumatic stress disorder symptoms in the long term.

Understanding the potential of digital therapies in implementing the standard of care for depression in Europe.

Depressive disorders represent the largest proportion of mental illnesses, and by 2030, they are expected to be the first cause of disability-adjusted life years [1]. The COVID-19 pandemic exacerbated prevalence and burden of depression and increased the occurrence of depressive symptoms in general population [2]. The urgency of implementing mental health services to address new barriers to care persuaded clinicians to use telemedicine to follow patients and stay in touch with them, and to explore digital therapeutics (DTx) as potential tools for clinical intervention [2]. The combination of antidepressants and psychotherapy is widely recommended for depression by international guidelines [3] but is less frequently applied in real-world practice. Commonly used treatments are pharmacological, but while being effective, some aspects such as adherence to the drug regimen, residual symptoms, resistance, lack of information, and stigma may hinder successful treatment. In case of less severe depression, standalone psychological therapies should be the first-line treatment option [3], but access to trained psychotherapists remains inequitable. DTx are evidence-based therapies driven by software programs to treat or complement treatment of a specific disease. DTx are classified as Medical Devices, and given their therapeutic purpose, they need to be validated through randomized controlled clinical trials, as for drug-based therapies. In the last 10 years, studies of digital interventions have proliferated; these studies demonstrate that digital interventions increase remission rates and lower the severity of depressive symptoms compared with waitlist, treatment as usual, and attention control conditions [4]. Despite the efficacy demonstrated in clinical trials, many of these tools never reach real-life patients; thus, it might be necessary to implement DTx in the public health system to expand access to valid treatment options. In this framework, DTx represent a good opportunity to help people with depression receive optimal psychotherapeutic care [5].

The effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial.

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 ± 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 ± 0.1 h vs. 4.9 ± 0.02; p < 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p < 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p < 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p < 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media.

The future of diagnosis in clinical neurosciences: Comparing multiple sclerosis and schizophrenia.

The ongoing developments of psychiatric classification systems have largely improved reliability of diagnosis, including that of schizophrenia. However, with an unknown pathophysiology and lacking biomarkers, its validity still remains low, requiring further advancements. Research has helped establish multiple sclerosis (MS) as the central nervous system (CNS) disorder with an established pathophysiology, defined biomarkers and therefore good validity and significantly improved treatment options. Before proposing next steps in research that aim to improve the diagnostic process of schizophrenia, it is imperative to recognize its clinical heterogeneity. Indeed, individuals with schizophrenia show high interindividual variability in terms of symptomatic manifestation, response to treatment, course of illness and functional outcomes. There is also a multiplicity of risk factors that contribute to the development of schizophrenia. Moreover, accumulating evidence indicates that several dimensions of psychopathology and risk factors cross current diagnostic categorizations. Schizophrenia shares a number of similarities with MS, which is a demyelinating disease of the CNS. These similarities appear in the context of age of onset, geographical distribution, involvement of immune-inflammatory processes, neurocognitive impairment and various trajectories of illness course. This article provides a critical appraisal of diagnostic process in schizophrenia, taking into consideration advancements that have been made in the diagnosis and management of MS. Based on the comparison between the two disorders, key directions for studies that aim to improve diagnostic process in schizophrenia are formulated. All of them converge on the necessity to deconstruct the psychosis spectrum and adopt dimensional approaches with deep phenotyping to refine current diagnostic boundaries.