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BackgroundThe development of neuroimaging biomarkers in patients with schizophrenia (SCZ) requires a refined clinical characterization. A limitation of the neuroimaging literature is the partial uptake of progress in characterizing disease-related features, particularly negative symptoms (NS) and cognitive impairment (CI). In the present study, we assessed NS and CI using up-to-date instruments and investigated the associations of abnormalities in brain resting-state (rs)-activity with disease-related features.MethodsSixty-two community-dwelling SCZ subjects participated in the study. Multiple regression analyses were performed with the rs-activity of nine regions of interest as dependent variables and disease-related features as explanatory variables.ResultsAttention/vigilance deficits were negatively associated with dorsal anterior cingulate rs-activity and, together with depression, were positively associated with right dorsolateral prefrontal cortex rs-activity. These deficits and impairment of Reasoning/problem-solving, together with conceptual disorganization, were associated with right inferior parietal lobule and temporal parietal junction rs-activity. Independent of other features, the NS Expressive Deficit domain was associated with the left ventral caudate, while the Motivational Deficit was associated with the dorsal caudate rs-activity.ConclusionNeurocognitive deficits and the two negative symptom domains are associated with different neural markers. Replications of these findings could foster the identification of clinically actionable biomarkers of poor functional outcomes.

Major depressive disorder (MDD) is a recurrent episodic mood disorder that represents the third leading cause of disability worldwide. In MDD, several factors can simultaneously contribute to its development, which complicates its diagnosis. According to practical guidelines, antidepressants are the first-line treatment for moderate to severe major depressive episodes. Traditional treatment strategies often follow a one-size-fits-all approach, resulting in suboptimal outcomes for many patients who fail to experience a response or recovery and develop the so-called “therapy-resistant depression”. The high biological and clinical inter-variability within patients and the lack of robust biomarkers hinder the finding of specific therapeutic targets, contributing to the high treatment failure rates. In this frame, precision medicine, a paradigm that tailors medical interventions to individual characteristics, would help allocate the most adequate and effective treatment for each patient while minimizing its side effects. In particular, multi-omic studies may unveil the intricate interplays between genetic predispositions and exposure to environmental factors through the study of epigenomics, transcriptomics, proteomics, metabolomics, gut microbiomics, and immunomics. The integration of the flow of multi-omic information into molecular pathways may produce better outcomes than the current psychopharmacological approach, which targets singular molecular factors mainly related to the monoamine systems, disregarding the complex network of our organism. The concept of system biomedicine involves the integration and analysis of enormous datasets generated with different technologies, creating a “patient fingerprint”, which defines the underlying biological mechanisms of every patient. This review, centered on precision medicine, explores the integration of multi-omic approaches as clinical tools for prediction in MDD at a single-patient level. It investigates how combining the existing technologies used for diagnostic, stratification, prognostic, and treatment-response biomarkers discovery with artificial intelligence can improve the assessment and treatment of MDD.

ObjectivesThe aim of the current study was 3-fold: 1) to examine the factorial structure of the Comprehensive Assessment of At-Risk Mental States (CAARMS) in help-seeking individuals undergoing an assessment on suspicion of psychosis risk; 2) to investigate the association of CAARMS factors with functioning; 3) and to test the association of any derived factors with the longitudinal outcome of transition to psychosis.MethodsThe study included 101 patients. First, a principal component analysis (PCA) was conducted using the Varimax rotation method. A minimum initial eigenvalues of greater than or equal to 1.0, analysis of Scree plots, percentage of variance explained by each component, reliability (Cronbach’s alpha) of factors above 0.7 and Parallel Analysis were the criteria used to determine the appropriate number of factors Second, Spearman correlations were run to analyze the relationship between CAARMS factors and sociodemographic and functional variables (i.e. age, schooling, Social and Occupational Functioning Assessment Scale-SOFAS- and Health of the Nation Outcome Scales-HoNOS- scores). Third, we performed a Logistic regression analysis to evaluate the association between baseline CAARMS factors and the risk of transition to psychosis at the 6-month follow-up.ResultsA total of 101 consecutive patiens were recruited. We found that: 1) a 6 factor model solution as the most appropriate, jointly accounting for 65% of the variance; 2) factors 1 (“negative-interpersonal”), 2 (“cognitive-disorganization”), 3 (“positive”), and 4 (“motor-physical changes”) were negatively correlated with SOFAS total score; factors 1, 2, and 3 showed positive correlations with HoNOS total score; factors 2 and 3 present similar patterns of correlations, factor 3 manifesting the strongest association with HoNOS symptoms, HONOS and SOFAS total score. Both factors 5 and 6 show significant associations with HoNOS behavioral impairment; 3) after 6 months 28 participants (30.1%) converted to psychosis. Factors 2 and 3 were positively associated with the risk of transition to psychosis; whereas, the factor 5 (“affective factor”) was negatively associated with the outcome variable.ConclusionsIt is thus crucial to recognize the type and severity of psychopathology in help-seeking individuals in order to intensive clinical monitoring of subclinical psychopathology risk profiles, and design specific care pathways.

Borderline personality disorder (BPD) is a severe and complex mental disorder that traditionally has been found to be more frequent in the female gender in clinical samples. More recently, epidemiological studies have provided conflicting data about the prevalence of borderline disorder in the two genders in community samples. In order to explain this heterogeneity, some authors hypothesized the presence of a bias in the diagnostic criteria thresholds (more prevalent in one gender than another), in the population sampling (community versus clinical), in the instruments of evaluation (clinician versus self-report measures), and in the diagnostic construct of BPD. Beyond the question of the different prevalence of the disorder between genders, the debate remains open as to how personality and clinical characteristics, and attitude toward treatments express themselves in the two genders. This narrative review is aimed to provide an updated overview of the differences among genders in BPD in terms of diagnosis, temperamental and clinical characteristics, comorbidities, findings of neuroimaging, and treatment attitudes. Studies that specifically investigated the gender differences in BPD patients are rather limited. Most of the investigations did not consider gender as a variable or were characterized by a significant imbalance between the two genders (more commonly in favor the female gender). The main results indicated that men were more likely to endorse the criteria “intense and inappropriate anger” and “impulsivity,” whereas women endorsed the criteria “chronic feelings of emptiness,” “affective instability,” and “suicidality/self-harm behaviors.” These findings reflect differences in temperament and symptoms of the two genders. Other relevant differences concern pattern of comorbidity, specific neurobiological mechanisms and attitude to treatments. Main limitations were that only one database was searched, time of publications was limited, non-English manuscripts were excluded, and the quality of each paper was not commented.

Abstract Background The conceptualization of negative symptoms (NS) in schizophrenia is still controversial. Recent confirmatory factor-analytic studies suggested that the bi-dimensional model (motivational deficit [MAP] and expressive deficit [EXP]) may not capture the complexity of NS structure, which could be better defined by a five-factor (five NS domains) or a hierarchical model (five NS domains as first-order factors, and MAP and EXP, as second-order factors). A validation of these models is needed to define the structure of NS. To evaluate the validity and temporal stability of the five-factor or the hierarchical structure of the brief negative symptom scale (BNSS) in individuals with schizophrenia (SCZ), exploring associations between these models with cognition, social cognition, functional capacity, and functioning at baseline and at 4 years follow-up. Methods Clinical variables were assessed using state-of-the-art tools in 612 SCZ at two-time points. The validity of the five-factor and the hierarchical models was analyzed through structural equation models. Results The two models had both a good fit and showed a similar pattern of associations with external validators at the two-time points, with minor variations. The five-factor solution had a slightly better fit. The associations with external validators favored the five-factor structure. Conclusions Our findings suggest that both five-factor and hierarchical models provide a valid conceptualization of NS in relation to external variables and that five-factor solution provides the best balance between parsimony and granularity to summarize the BNSS structure. This finding has important implications for the study of pathophysiological mechanisms and the development of new treatments.

Correct nutrition and diet are directly correlated with mental health, functions of the immune system, and gut microbiota composition. Diets with a high content of some nutrients, such as fibers, phytochemicals, and short-chain fatty acids (omega-3 fatty acids), seem to have an anti-inflammatory and protective action on the nervous system. Among nutraceuticals, supplementation of probiotics and omega-3 fatty acids plays a role in improving symptoms of several mental disorders. In this review, we collect data on the efficacy of nutraceuticals in patients with schizophrenia, autism spectrum disorders, major depression, bipolar disorder, and personality disorders. This narrative review aims to provide an overview of recent evidence obtained on this topic, pointing out the direction for future research.

ObjectivesThe aim of this study was to evaluate the relative contributions of visual learning and conceptual disorganization to specific metacognitive domains in a sample of outpatients with stable schizophrenia.MethodsA total of 92 consecutive outpatients with stable schizophrenia were recruited in a cross-sectional study. We analyzed the data with five path analyses based on multiple regressions to analyze the specific effect of visual learning on metacognitive capacity and metacognitive domains and the possible mediating role of conceptual disorganization.ResultsWe found that (i) visual learning was negatively correlated to metacognitive capacity and its domains on the one hand and conceptual disorganization on the other hand; (ii) conceptual disorganization was negatively associated with metacognition and its domains; and (iii) when the mediation effect was considered, conceptual disorganization fully mediated the relationship between visual learning and mastery, whereas it served as a partial mediator of the effect of visual learning on the other metacognition domains, i.e., self-reflectivity, understanding others’ mind, and decentration.ConclusionThese results delineate an articulated panorama of relations between different dimensions of metacognition, visual learning, and conceptual disorganization. Therefore, studies unable to distinguish between different components of metacognition fail to bring out the possibly varying links between neurocognition, disorganization, and metacognition.

The use of holograms in exhibition design and the new frontier of inclusive communication to the public: how holograms enrich the cultural experience and how digital technology synthesizes the analog into experiences that amplify the perception of art and its meaning. When introduced to the topic of holograms for the first time, one's mind may wander to a diverse archive of pop culture and science fiction, transporting us to the distant worlds of Star Wars or Star Trek, or to the advertisements from Back to the Future. At first glance, holograms appear as nothing more than a fantasy, a glimpse into a technology seemingly too advanced for our time. However, enthusiasts know that the era of holograms has begun, and we are already engaged in an ongoing technological pursuit. Experts in the field are aware that technology's evolution has impressively expanded the horizons of hologram applications.

Background The structure of negative symptoms of schizophrenia is still a matter of controversy. Although a two-dimensional model (comprising the expressive deficit dimension and the motivation and pleasure dimension) has gained a large consensus, it has been questioned by recent investigations. Aims To investigate the latent structure of negative symptoms and its stability over time in people with schizophrenia using network analysis. Method Negative symptoms were assessed in 612 people with schizophrenia using the Brief Negative Symptom Scale (BNSS) at baseline and at 4-year follow-up. A network invariance analysis was conducted to investigate changes in the network structure and strength of connections between the two time points. Results The network analysis carried out at baseline and follow-up, supported by community detection analysis, indicated that the BNSS's items aggregate to form four or five distinct domains (avolition/asociality, anhedonia, blunted affect and alogia). The network invariance test indicated that the network structure remained unchanged over time (network invariance test score 0.13; P = 0.169), although its overall strength decreased (6.28 at baseline, 5.79 at follow-up; global strength invariance test score 0.48; P = 0.016). Conclusions The results lend support to a four- or five-factor model of negative symptoms and indicate overall stability over time. These data have implications for the study of pathophysiological mechanisms and the development of targeted treatments for negative symptoms.

IntroductionThe spread of the coronavirus disease 2019 (COVID-19) pandemic and the subsequent restrictions significantly affected mental health, especially major depressive disorder (MDD) whose incidence increased by 27.6% in 2020, after the COVID-19 outbreak. Few studies focused on the impact of the pandemic on the clinical characteristics of outpatients with MDD and even fewer on inpatients admitted for a major depressive episode (MDE). We aimed to compare the characteristics of MDD of two groups of patients admitted for an MDE before and after the pandemic outbreak and to investigate which variables are significantly related to post-lockdown hospitalizations.MethodsThis retrospective study included 314 patients with MDD hospitalized from January 2018 to December 2021 for an MDE (DSM-5) before (n = 154) and after (n = 160) the Italian lockdown (9th of March 2020). We compared patients' sociodemographic and clinical characteristics. The characteristics significantly different between the two groups were included in a logistic regression to identify the factors more strictly associated with post-lockdown hospitalizations.ResultsDuring post-lockdown hospitalization, we found a higher rate of severe MDE (33 patients, 21.4%, in the pre-lockdown and 55 patients, 34.4%, in the post), MDE with psychotic features (3 patients, 2.0%, in the pre-lockdown and 11 patients, 6.9%, in the post-lockdown), and suicidal ideation (42, 27.3%, in the pre-lockdown and 67, 41.9%, in the post-lockdown), with a lower proportion of patients followed by psychiatric services before admission (106 patients, 68.8%, in the pre-lockdown and 90 patients, 56.3%, in the post-lockdown) and a higher percentage of them in treatment with psychotherapy (18 patients, 11.7% in the pre-lockdown and 32, 20.0%, in the post-lockdown) and more frequent increase of the antidepressant dosage (16 patients, 10.4% in the pre-lockdown and 32 patients, 20.0% in the post-lockdown) and adoption of augmentation strategies (13 patients, 8.4%, in the pre-lockdown and 26 patients, 16.3%, in the post-lockdown) to treat the MDE. In the regression model, post-lockdown hospitalizations were significantly associated with suicidal ideation (OR = 1.86; p = 0.016) and psychotic features (OR = 4.41; p = 0.029) at admission, the increase in the antidepressant daily dose (OR = 2.45; p = 0.009), and the employment of an augmentation therapy (OR = 2.25; p = 0.029).DiscussionThese results showed an association between the COVID-19 pandemic and the occurrence of MDE with more severe clinical features. This might be true also for future calamities, suggesting that in these emergency contexts, patients with MDD would require more attention, resources, and intense treatments with a specific focus on suicide prevention.

Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving personal recovery from the disorder. Long-acting injectable second-generation antipsychotics (SGA-LAIs) represent a valid therapeutic option for the treatment of SZ as they guarantee good efficacy and adherence to treatment. The aim of this rapid review is to summarize the evidence on the efficacy of SGA-LAIs in improving subjective quality of life, well-being, and satisfaction. The PubMed database was searched for original studies using SGA, LAI, risperidone, paliperidone, aripiprazole, olanzapine, SZ, and psychosis as keywords. Twenty-one studies were included: 13 clinical trials, 7 observational studies, and 1 post hoc analysis. It has been shown that SGA-LAIs bring an improvement to specific domains of subjective and self-rated quality of life, well-being, or satisfaction in prospective observational studies without a control arm and in randomized controlled trials versus placebo. The superiority of SGA-LAIs as compared with oral equivalents and haloperidol-LAI has been reported by some randomized controlled and observational studies. Although promising, the evidence is still limited because of the lack of studies and several methodological issues concerning the choice of the sample, the evaluation of the outcome variables, and the study design. New methodologically sound studies are needed.

Abstract Background Deficits in social cognition (SC) are significantly related to community functioning in schizophrenia (SZ). Few studies investigated longitudinal changes in SC and its impact on recovery. In the present study, we aimed: (a) to estimate the magnitude and clinical significance of SC change in outpatients with stable SZ who were assessed at baseline and after 4 years, (b) to identify predictors of reliable and clinically significant change (RCSC), and (c) to determine whether changes in SC over 4 years predicted patient recovery at follow-up. Methods The reliable change index was used to estimate the proportion of true change in SC, not attributable to measurement error. Stepwise multiple logistic regression models were used to identify the predictors of RCSC in a SC domain (The Awareness of Social Inference Test [TASIT]) and the effect of change in TASIT on recovery at follow-up. Results In 548 participants, statistically significant improvements were found for the simple and paradoxical sarcasm of TASIT scale, and for the total score of section 2. The reliable change index was 9.8. A cut-off of 45 identified patients showing clinically significant change. Reliable change was achieved by 12.6% and RCSC by 8% of participants. Lower baseline TASIT sect. 2 score predicted reliable improvement on TASIT sect. 2. Improvement in TASIT sect. 2 scores predicted functional recovery, with a 10-point change predicting 40% increase in the probability of recovery. Conclusions The RCSC index provides a conservative way to assess the improvement in the ability to grasp sarcasm in SZ, and is associated with recovery.

Abstract Intrinsic motivation was described as the mental process of pursuing a task or an action because it is enjoyable or interesting in itself and was found to play a central role in the determination of the functional outcome of schizophrenia. Neurocognition is one of the most studied determinants of intrinsic motivation in clinically stable schizophrenia while little is known about the role of insight. Following this need we decided to focus on the contribution of different aspects of insight and of neurocognition to intrinsic motivation in a large sample (n = 176) of patients with stable schizophrenia. We performed three hierarchical linear regressions from which resulted that, among different insight aspects, the ability to correctly attribute signs and symptoms to the mental disorder made the strongest contribution to intrinsic motivation. Neurocognition, also, was significantly related to intrinsic motivation when analyzed simultaneously with insight. Moreover, even after accounting for sociodemographic and clinical variables significantly correlated with intrinsic motivation, the relationship between insight and neurocognition and intrinsic motivation remained statistically significant. These findings put the emphasis on the complex interplay between insight, neurocognition, and intrinsic motivation suggesting that interventions targeting both insight and neurocognition might possibly improve this motivational deficit in stable schizophrenia should.

Background: Partial adherence to antipsychotics is the most common cause of relapses and rehospitalization in patients with schizophrenia (SZ), leading to higher health care costs and psychosocial disability. The use of long-acting injectable (LAI) antipsychotics may improve therapeutic continuity and adherence to treatment. Objective: To assess the effectiveness of switching from oral antipsychotics (OAs) to long-acting antipsychotics. Methods: This 1-year mirror-image study evaluated the effect of switching from OAs to LAIs on the reduction of psychiatric hospitalizations and the improvement of global functioning in patients with schizophrenia. Differences in outcomes between second-generation (SGA) LAIs and first-generation (FGA) LAIs were also analyzed. Results: In all, 166 patients were included: 32.5% treated by FGA-LAIs and 67.5% by SGA-LAIs. There was an overall reduction of 71% in the average number of hospital admissions and an overall improvement of 29.3% in the Global Assessment of Functioning (GAF) score between the previous 12 months and the 12 months following the switching to LAIs. Patients who switched to SGA-LAIs had no significant differences in hospitalization occurrences but a significant improvement in GAF scores when compared with patients who switched to FGA-LAIs. Conclusion: Our results suggest that using LAIs could be the most adequate treatment choice for SZ patients with a high risk of relapse and low adherence rate. Patients with poorer social functioning may be ideal candidates for SGA-LAIs treatment. Our findings may be of particular interest from a clinical and health care management perspective.

Abstract A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n = 618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients’ reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin’s concordance correlation, Somers’ D, and Bland–Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients’ self-evaluation of functioning was higher than caregivers’ in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers’ ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program.

Abstract Patients with schizophrenia (SCZ) have a core impairment in the communicative-pragmatic domain, characterized by severe difficulties in correctly inferring the speaker’s communicative intentions. While several studies have investigated pragmatic performance of patients with SCZ, little research has analyzed the errors committed in the comprehension of different communicative acts. The present research investigated error patterns in 24 patients with SCZ and 24 healthy controls (HC) during a task assessing the comprehension of different communicative acts, i.e., sincere, deceitful and ironic, and their relationship with the clinical features of SCZ. We used signal detection analysis to quantify participants’ ability to correctly detect the speakers’ communicative intention, i.e., sensitivity, and their tendency to wrongly perceive a communicative intention when not present, i.e., response bias. Further, we investigated the relationship between sensitivity and response bias, and the clinical features of the disorder, namely symptom severity, pharmacotherapy, and personal and social functioning. The results showed that the ability to infer the speaker’s communicative intention is impaired in SCZ, as patients exhibited lower sensitivity, compared to HC, for all the pragmatic phenomena evaluated, i.e., sincere, deceitful, and ironic communicative acts. Further, we found that the sensitivity measure for irony was related to disorganized/concrete symptoms. Moreover, patients with SCZ showed a stronger response bias for deceitful communicative acts compared to HC: when committing errors, they tended to misattribute deceitful intentions more often than sincere and ironic ones. This tendency to misattribute deceitful communicative intentions may be related to the attributional bias characterizing the disorder.

Schizophrenia is among the fifteen most disabling diseases worldwide. Negative symptoms (NS) are highly prevalent in schizophrenia, negatively affect the functional outcome of the disorder, and their treatment is difficult and rarely specifically investigated. Serotonin-dopamine activity modulators (SDAMs), of which aripiprazole, cariprazine, brexpiprazole, and lumateperone were approved for schizophrenia treatment, represent a possible therapy to reduce NS. The aim of this rapid review is to summarize the evidence on this topic to make it readily available for psychiatrists treating NS and for further research. We searched the PubMed database for original studies using SDAM, aripiprazole, cariprazine, brexpiprazole, lumateperone, schizophrenia, and NS as keywords. We included four mega-analyses, eight meta-analyses, two post hoc analyses, and 20 clinical trials. Aripiprazole, cariprazine, and brexpiprazole were more effective than placebo in reducing NS. Only six studies compared SDAMs with other classes of antipsychotics, demonstrating a superiority in the treatment of NS mainly for cariprazine. The lack of specific research and various methodological issues, related to the study population and the assessment of NS, may have led to these partial results. Here, we highlight the need to conduct new methodologically robust investigations with head-to-head treatment comparisons and long-term observational studies on homogeneous groups of patients evaluating persistent NS with first- and second-generation scales, namely the Brief Negative Symptom Scale and the Clinical Assessment Interview for Negative Symptoms. This rapid review can expand research on NS therapeutic strategies in schizophrenia, which is fundamental for the long-term improvement of patients’ quality of life.

Von Economo neurons (VENs) are rod, stick, or corkscrew cells mostly located in layer V of the frontoinsular and anterior cingulate cortices. VENs are projection neurons related to human-like social cognitive abilities. Post-mortem histological studies found VEN alterations in several neuropsychiatric disorders, including schizophrenia (SZ). This pilot study aimed to evaluate the role of VEN-containing areas in shaping patterns of resting-state brain activation in patients with SZ (n = 20) compared to healthy controls (HCs; n = 20). We performed a functional connectivity analysis seeded in the cortical areas with the highest density of VENs followed by fuzzy clustering. The alterations found in the SZ group were correlated with psychopathological, cognitive, and functioning variables. We found a frontotemporal network that was shared by four clusters overlapping with the salience, superior-frontal, orbitofrontal, and central executive networks. Differences between the HC and SZ groups emerged only in the salience network. The functional connectivity of the right anterior insula and ventral tegmental area within this network were negatively correlated with experiential negative symptoms and positively correlated with functioning. This study provides some evidence to show that in vivo, VEN-enriched cortical areas are associated with an altered resting-state brain activity in people with SZ.

(1) Background: although studies of cognitive functions are still limited in borderline personality disorder (BPD), the initial evidence suggested that BPD patients have deficits of executive functions and social cognition. In addition, patients who report physical and psychic traumatic experiences in childhood and adolescence show considerable neurocognitive impairment and severe BPD symptoms. The present study has a twofold aim: (1) to evaluate the differences in neurocognitive performances between BPD patients and healthy controls and (2) to verify in the BPD patients group whether neurocognitive deficits have the role of mediating the effect of early traumas on BPD psychopathology. (2) Methods: 69 subjects were enrolled: 38 outpatients with a diagnosis of BPD (DSM-5) and 31 healthy controls. BPD patients were tested with the Borderline Personality Disorder Severity Index (BPDSI), and the Childhood Trauma Questionnaire–Short Form (CTQ-SF). All subjects were evaluated with the Iowa Gambling task (IGT), the Berg card sorting test (BCST), the Tower of London task (ToL), and the Reading-the-mind-in-the-eyes-test (RMET). Statistical analysis was performed with the analysis of variance to compare the cognitive performances between BPD patients and controls. A mediation analysis was conducted with the Sobel Test in the BPD patients group. The significance level was p ≤ 0.05. (3) Results: significant differences between the two groups were found for several parameters of all the cognitive tests examined: BCST, IGT, ToL, and RMET. Mediation analysis with the Sobel test demonstrated that the percentage of correct answers in the BCST (BCSTc) and the RMET score significantly mediated the relation between the CTQ total score and BPDSI total score. (4) Conclusions: BPD patients showed an impairment of the following executive functions: set shifting, decision making, planning and problem solving, and social cognition abilities, in comparison with controls. Our results suggested that the effect of early trauma on BPD psychopathology was mediated by a deficit in two cognitive domains: cognitive flexibility and social cognition.

The aim of the present study was to examine the neurobiological correlates of the two negative symptom domains of schizophrenia, the Motivational Deficit domain (including avolition, anhedonia, and asociality) and the Expressive Deficit domain (including blunted affect and alogia), focusing on brain areas that are most commonly found to be associated with negative symptoms in previous literature. Resting-state (rs) fMRI data were analyzed in 62 subjects affected by schizophrenia (SZs) and 46 healthy controls (HCs). The SZs, compared to the HCs, showed higher rs brain activity in the right inferior parietal lobule and the right temporoparietal junction, and lower rs brain activity in the right dorsolateral prefrontal cortex, the bilateral anterior dorsal cingulate cortex, and the ventral and dorsal caudate. Furthermore, in the SZs, the rs brain activity in the left orbitofrontal cortex correlated with negative symptoms (r = −0.436, p = 0.006), in particular with the Motivational Deficit domain (r = −0.424, p = 0.002), even after controlling for confounding factors. The left ventral caudate correlated with negative symptoms (r = −0.407, p = 0.003), especially with the Expressive Deficit domain (r = −0.401, p = 0.003); however, these results seemed to be affected by confounding factors. In line with the literature, our results demonstrated that the two negative symptom domains might be underpinned by different neurobiological mechanisms.

Therapeutic drug monitoring (TDM) receives growing interest in different psychiatric clinical settings (emergency, inpatient, and outpatient services). Despite its usefulness, TDM remains underemployed in mental health. This is partly due to the need for evidence about the relationship between drug serum concentration and efficacy and tolerability, both in the general population and even more in subpopulations with atypical pharmacokinetics. This work aims at reviewing the scientific literature published after 2017, when the most recent guidelines about the use of TDM in mental health were written. We found 164 pertinent records that we included in the review. Some promising studies highlighted the possibility of correlating early drug serum concentration and clinical efficacy and safety, especially for antipsychotics, potentially enabling clinicians to make decisions on early laboratory findings and not proceeding by trial and error. About populations with pharmacokinetic peculiarities, the latest studies confirmed very common alterations in drug blood levels in pregnant women, generally with a progressive decrease over pregnancy and a very relevant dose-adjusted concentration increase in the elderly. For adolescents also, several drugs result in having different dose-related concentration values compared to adults. These findings stress the recommendation to use TDM in these populations to ensure a safe and effective treatment. Moreover, the integration of TDM with pharmacogenetic analyses may allow clinicians to adopt precise treatments, addressing therapy on an individual pharmacometabolic basis. Mini-invasive TDM procedures that may be easily performed at home or in a point-of-care are very promising and may represent a turning point toward an extensive real-world TDM application. Although the highlighted recent evidence, research efforts have to be carried on: further studies, especially prospective and fixed-dose, are needed to replicate present findings and provide clearer knowledge on relationships between dose, serum concentration, and efficacy/safety.

The role of childhood trauma in the development of borderline personality disorder (BPD) in young age has long been studied. The most accurate theoretical models are multifactorial, taking into account a range of factors, including early trauma, to explain evolutionary pathways of BPD. We reviewed studies published on PubMed in the last 20 years to evaluate whether different types of childhood trauma, like sexual and physical abuse and neglect, increase the risk and shape the clinical picture of BPD. BPD as a sequela of childhood traumas often occurs with multiple comorbidities (e.g. mood, anxiety, obsessive-compulsive, eating, dissociative, addictive, psychotic, and somatoform disorders). In such cases it tends to have a prolonged course, to be severe, and treatment-refractory. In comparison with subjects who suffer from other personality disorders, patients with BPD experience childhood abuse more frequently. Adverse childhood experiences affect different biological systems (HPA axis, neurotransmission mechanisms, endogenous opioid systems, gray matter volume, white matter connectivity), with changes persisting into adulthood. A growing body of evidence is emerging about interaction between genes (e.g. FKBP5 polymorphisms and CRHR2 variants) and environment (physical and sexual abuse, emotional neglect).

We aimed to evaluate in a sample of outpatients with schizophrenia (SCZ) the effectiveness of a cognitive remediation (CR) program (through the use of the Cogpack software) [computer-assisted CR (CACR)] in addition to standard therapy on cognitive outcomes as compared with that in a control active group (CAG) and to highlight a possible effect on social cognition (SC), metacognition, symptomatology, and real-world functioning. Of the 66 subjects enrolled, 33 were allocated to CACR and 33 to the CAG. Twenty-three patients in the CACR group and 25 subjects in the CAG completed at least 80% of the 48 prescribed CACR sessions, performed twice a week, for a total of 24 weeks of treatment. A significant time × group interaction was evident, suggesting that patients undergoing CACR intervention improved in specific metacognitive sub-functions (understanding others' mind and mastery), some cognitive domains (verbal learning processing speed, visual learning, reasoning, and problem solving) (h2 = 0.126), depressive symptoms, SC, awareness of symptoms, and real-world functioning domains (community activities and interpersonal relationships) more significantly than did patients undergoing CAG. The most noticeable differential improvement between the two groups was detected in two metacognitive sub-functions (understanding others' mind and mastery), in verbal learning, in interpersonal relationship, and in depressive symptomatology, achieving large effect sizes. These are encouraging findings in support of the possible integration of CACR in rehabilitation practice in the Italian mental health services.

Introduction: Investigations on predictors of real-world functioning were mainly performed in patients with schizophrenia, while fewer studies have been conducted in other psychiatric disorders. Objective: Our objective was to identify clinical, socio-demographic, and illness-related predictors of real-world functioning during 12 months of standard treatments in outpatients with different diagnoses. Methods: Outpatients (n = 1019) with schizophrenia (SZ), major depressive disorder (MDD), bipolar disorder (BD), and borderline personality disorder (BPD) were evaluated with the following tools: SCID-5-CV and SCID-5-PD, CGI-S, SAT-P, DAI-10, and PSP. Change of PSP (ΔPSP) between baseline and 12 months was used as the dependent variable in multiple regression analysis. Results: Higher PSP score at baseline and the achievement of main milestones predicted better functioning after follow-up in all subgroups of patients, with the exception of BD. In the total sample, ΔPSP was related to age of onset, treatments, and quality of life, and inversely related to psychiatric anamnesis, antidepressants, and global symptoms. In SZ, ΔPSP was related to adherence and quality of life. In MDD, ΔPSP was related to psychotherapy and quality of life, and inversely related to antidepressants and global symptoms. In BD, ΔPSP was related to age of onset, antipsychotics, and quality of life, while it was inversely related to psychiatric anamnesis. In BPD, antipsychotics, mood stabilizers, psychotherapy, and quality of life were directly related to ΔPSP, while suicidal attempts and global symptoms had an inverse relation. Conclusions: Several socio-demographic and illness-related variables predicted improvement of real-world functioning, besides psychopathology and severity of the disease.

Background: COVID-19 pandemic has affected the physical health, psychological wellbeing, and mental health of the whole population. Young people are among those most at risk of developing mental health symptoms or disorders related to the pandemic. Purpose: the present narrative review is aimed at providing an updated overview of the current literature concerning the psychological impact of the SARS-CoV-2 infection but also of the COVID-19 outbreak, environmental restriction, and social distancing on mental health outcomes among the youth population aged between 15 and 25 years. Methods: in December 2021, an electronic search on this topic was performed on PubMed. Relevant publications from January 2020 until December 2021 were included. Findings: 53 cross-sectional studies, 26 longitudinal studies, 4 ecological studies, 1 qualitative study, and 1 systematic review were included. We found many methodological limitations in the studies included, especially poor choice of study samples and short follow-ups. Little literature was in support of a strong relationship between SARS-CoV-2 infection and consequences on youth mental health. On the contrary, many studies showed how extraordinary measures to limit the spread of the virus have impacted young people in terms of onset of new mental disorders and symptoms, suicidality, and access to emergency psychiatric services. Depressive and anxiety symptoms and disorders show the greatest increase in incidence, especially in girls and young women. Conclusions: it seems important to pay attention to the mental health of young people in relation to the consequences of the COVID-19 pandemic. However, studies with more robust methodologies and longer follow-ups are needed to establish precise indications for targeted interventions in this context.

ObjectiveThe present study reviews predictive models used to improve prediction of psychosis onset in individuals at clinical high risk for psychosis (CHR), using clinical, biological, neurocognitive, environmental, and combinations of predictors.MethodsA systematic literature search on PubMed was carried out (from 1998 through 2019) to find all studies that developed or validated a model predicting the transition to psychosis in CHR subjects.ResultsWe found 1,406 records. Thirty-eight of them met the inclusion criteria; 11 studies using clinical predictive models, seven studies using biological models, five studies using neurocognitive models, five studies using environmental models, and 18 studies using combinations of predictive models across different domains. While the highest positive predictive value (PPV) in clinical, biological, neurocognitive, and combined predictive models were relatively high (all above 83), the highest PPV across environmental predictive models was modest (63%). Moreover, none of the combined models showed a superiority when compared with more parsimonious models (using only neurocognitive, clinical, biological, or environmental factors).ConclusionsThe use of predictive models may allow high prognostic accuracy for psychosis prediction in CHR individuals. However, only ten studies had performed an internal validation of their models. Among the models with the highest PPVs, only the biological and neurocognitive but not the combined models underwent validation. Further validation of predicted models is needed to ensure external validity.

Abstract Background Autism spectrum disorders (ASDs) and schizophrenia spectrum disorders (SSDs), although conceptualized as separate entities, may share some clinical and neurobiological features. ASD symptoms may have a relevant role in determining a more severe clinical presentation of schizophrenic disorder but their relationships with cognitive aspects and functional outcomes of the disease remain to be addressed in large samples of individuals. Aims To investigate the clinical, cognitive, and functional correlates of ASD symptoms in a large sample of people diagnosed with schizophrenia. Methods The severity of ASD symptoms was measured with the PANSS Autism Severity Scale (PAUSS) in 921 individuals recruited for the Italian Network for Research on Psychoses multicenter study. Based on the PAUSS scores, three groups of subjects were compared on a wide array of cognitive and functional measures. Results Subjects with more severe ASD symptoms showed a poorer performance in the processing speed (p = 0.010), attention (p = 0.011), verbal memory (p = 0.035), and social cognition (p = 0.001) domains, and an overall lower global cognitive composite score (p = 0.010). Subjects with more severe ASD symptoms also showed poorer functional capacity (p = 0.004), real-world interpersonal relationships (p

• Better insight seems associated with depressive symptoms in schizophrenia. • Network analyses were used to explore this association in a large sample. • Insight was associated with self-depreciation, guilt, and suicidal ideation. • Although cross-sectional, data suggest causal direction from insight to depression.

Borderline personality disorder (BPD) is a severe and heterogeneous mental disorder that is known to have the onset in young age, often in adolescence. For this reason, it is of fundamental importance to identify clinical conditions of childhood and adolescence that present a high risk to evolve in BPD. Investigations indicate that early borderline pathology (before 19 years) predict long-term deficits in functioning, and a higher percentage of these patients continue to present some BPD symptoms up to 20 years. There is a general accordance among investigators that good competence in both childhood and early adulthood is the main predictive factor of excellent recovery in BPD patients. Some authors suggest that specific childhood personality traits can to be considered precursors of adult BPD, as well as some clinical conditions: disruptive behaviours, disturbance in attention and emotional regulation, conduct disorders, substance use disorders, and attention-deficit-hyperactivity disorder. Unfortunately, diagnosis and treatment of BPD is usually delayed, also because some clinicians are reluctant to diagnose BPD in younger individuals. Instead, the early identification of BPD symptoms have important clinical implications in terms of precocious intervention programs, and guarantees that young people with personality disorders obtain appropriate treatments. This review is aimed to collect the current evidences on early risk and protective factors in young people that may predict BPD onset, course, and outcome.

Primary psychosis, which includes schizophrenia and other psychoses not caused by other psychic or physical conditions, has a strong impact worldwide in terms of disability, suffering and costs. Consequently, improvement of strategies to reduce the incidence and to improve the prognosis of this disorder is a current need. The purpose of this work is to review the current scientific literature on the main risk and protective factors of primary psychosis and to examine the main models of prevention, especially those related to the early detection of the onset. The conditions more strongly associated with primary psychosis are socio-demographic and economic factors such as male gender, birth in winter, ethnic minority, immigrant status, and difficult socio-economic conditions while the best-established preventive factors are elevated socio-economic status and an economic well-being. Risk and protective factors may be the targets for primordial, primary, and secondary preventive strategies. Acting on modifiable factors may reduce the incidence of the disorder or postpone its onset, while an early detection of the new cases enables a prompt treatment and a consequential better prognosis. According to this evidence, the study of the determinants of primary psychosis has a pivotal role in designing and promoting preventive policies aimed at reducing the burden of disability and suffering of the disorder.

Personality disorders (PDs) exert a great toll on health resources, and this is especially true for borderline personality disorder (BPD). As all PDs, BPD arises during adolescence or young adulthood. It is therefore important to detect the presence of this PD in its earlier stages in order to initiate appropriate treatment, thus ameliorating the prognosis of this condition. This review aims to highlight the issues associated with BPD diagnosis in order to promote its early detection and treatment. To do so, we conducted a search on PubMed database of current evidence regarding BPD early diagnosis, focusing on risk factors, which represent important conditions to assess during young patient evaluation, and on diagnostic tools that can help the clinician in the assessment process. Our findings show how several risk factors, both environmental and genetic/neurobiological, can contribute to the onset of BPD and help identify at-risk patients who need careful monitoring. They also highlight the importance of a careful clinical evaluation aided by psychometric tests. Overall, the evidence gathered confirms the complexity of BDP early detection and its crucial importance for the outcome of this condition.

Cognitive impairment is currently considered a core feature of schizophrenia (SZ) and is gaining attention as a fundamental therapeutic target. Standard treatment for SZ involves the use of antipsychotics that are successfully used to control positive symptoms and disorganized behaviour. However, it is still unclear whether they are effective on social cognition (SC) impairment. Furthermore, different medications are currently being studied to improve SC in patients with SZ. A literature search on this topic was conducted using the PubMed database. All kinds of publications (i.e., reviews, original contributions and case reports) written in English and published in the last 15 years were included. The aim of our literature review is to draw a picture of the current state of the pharmacological treatment of SC impairment in SZ.

There is increasing awareness of the importance of polyunsaturated fatty acids (PUFAs) for optimal brain development and function. In recent decades, researchers have confirmed the central role of PUFAs in a variety of patho-physiological processes. These agents modulate the mechanisms of brain cell signalling including the dopaminergic and serotonergic pathways. Therefore, nutritional insufficiencies of PUFAs may have adverse effects on brain development and developmental outcomes. The role of n-3 PUFAs has been studied in several psychiatric disorders in adulthood: schizophrenia, major depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, eating disorders, substance use disorder, and borderline personality disorder. In contrast to the great number of studies conducted in adults, there are only limited data on the effects of n-3 PUFA supplementation in children and adolescents who suffer from mental disorders or show a high risk of developing psychiatric disorders. The aim of this review is to provide a complete and updated account of the available evidence of the impact of polyunsaturated fatty acids on developmental psychopathology in children and adolescents and the effect of fatty acid supplementation during developmental milestones, particularly in high-risk populations of children with minimal but detectable signs or symptoms of mental disorders.

The onset of prodromal symptoms in subjects who are at familial or clinical risk for bipolar disorder could be considered as an important alarm bell for the development of the disease and should be carefully detected. The management of prodromes in bipolar high-risk patients appears to be an important means of prevention; nevertheless, at the moment, there aren’t clear and widely shared treatment indications. The aim of this review is to summarize the available treatment options (pharmacological, psychosocial and nutraceutical) for the management of prodromal symptoms in subjects who are at familial or clinical risk for bipolar disorder.

Identity disturbance is a core feature of borderline personality disorder (BPD). Autobiographical memory is a process of reflective thinking through which we form links between elements of life and self. It can be considered as an indirect index of identity integration. The present study was aimed to investigate the differences in brain activity patterns between BPD patients with identity diffusion and healthy controls using fMRI. We enrolled 24 BPD patients and 24 healthy controls. Identity integration in patients and controls was assessed with the Identity Disturbance Questionnaire (IDQ) score and was significantly different (p = 0.001). We analysed hemodynamic response in the regions of interest during presentation of resolved and unresolved life events. With reference to the condition “resolved”, increased cerebral activity in right anterior cingulate cortex (ACC), right medial prefrontal cortex (MPFC), right dorsolateral prefrontal cortex (DLPFC), and bilateral insula was registered in BPD patients compared with controls. In the condition “unresolved”, increased brain activity was observed in patients in bilateral ACC, bilateral DLPFC, and right temporo-parietal junction. Hyperactivity in ACC and DLPFC in BPD patients with both conditions (resolved and unresolved contexts) may be due to an inefficient attempt to reconstruct a coherent narrative of life events (resolved or not).

Background: Clinical and functional outcome improvement in psychotic disorders is a challenge for the investigators. Recent advances offered opportunities for ameliorating the course of the illness during its early stages and for identifying treatment-resistant patients. Patients who had not response to two different antipsychotics, administered at correct doses for a sufficient period, can be operationally considered treatment-resistant. Available evidence suggested that the response's trajectory to the antipsychotic treatment revealed that a small proportion of subjects are poor responders (8.2%), the majority of patients have a moderate response (76.4%), and only 15.4% can be considered rapid responders with the greatest magnitude of response. Patients with first episode of psychosis generally obtain a more favorable response profile. Nevertheless, in around 25% of these patients symptoms of psychosis persist with a worse long-term course of illness.Objectives: The aim of this review is to report current evidences on the main predictors of treatment non-response in patients at early stage of psychosis.Methods: We used a specific string that guaranteed a high sensitive search in pubmed. We included the following types of publications: randomized-controlled trials, observational studies, longitudinal studies, retrospective studies, case-control studies, open-label investigations, cohort studies, and reviews. Publications must concern predictors of treatment resistance in early psychosis.Results: Forty-seven records were included: 5 reviews, 3 meta-analyses, 22 longitudinal studies, 2 retrospective studies, 1 naturalistic study, 6 randomized controlled trials, 2 open-label studies, 2 case-control studies, 4 cohort studies, 2 retrospective studies. Several factors were identified as predictors of treatment resistance: lower premorbid functioning; lower level of education; negative symptoms from first psychotic episode; comorbid substance use; younger age at onset; lack of early response; non-adherence to treatment; and longer duration of untreated psychosis. The role of gender and marital status is still controversial. More evidences are needed about neurobiological, genetic, and neuroimaging factors.Conclusions: The identification of specific predictive factors of treatment resistance in patients with first episode of psychosis ameliorates the quality of clinical management of these patients in the critical early phase of schizophrenia.

It is the focus of increasing interest to investigate the effects of long-chain n-3 and long-chain n-6 polyunsaturated fatty acids (LC n-3 PUFAs; LC n-6 PUFAs) on psychiatric symptoms in a transdiagnostic perspective. There is some evidence that low levels of LC n-3 PUFAs and a higher ratio of LC n-6 to LC n-3 PUFAs in plasma and blood cells are associated with aggressive and impulsive behaviours. Therefore, implementation of LC n-3 PUFAs may produce positive effects on hostility, aggression, and impulsivity in both psychiatric and non-psychiatric samples across different stages of life. A possible mechanism of action of LC n-3 PUFAs in conditions characterized by a high level of impulsivity and aggression is due to the effect of these compounds on the serotonin system and membrane stability. Studies that evaluated the effects of LC n-3 PUFAs on impulsivity and aggressiveness indicated that addition of rather low doses of these agents to antipsychotic treatment might reduce agitation and violent behaviours in psychosis, attention deficit hyperactivity disorder, personality disorders, and impulsive control and conduct disorders. The present review is aimed at examining and discussing available data from recent trials on this topic.

The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.

In the central nervous system omega-3 fatty acids modulate cell signaling and affect dopaminergic and serotonergic pathways. On this basis, a new application for omega-3 fatty acids has been proposed, concerning the treatment of several psychiatric disorders. The present article is an update of a previous systematic review and is aimed to provide a complete report of data published in the period between 1980 and 2019 on efficacy and tolerability of omega-3 fatty acids in psychiatric disorders. In July 2019, an electronic search on PUBMED, Medline and PsychINFO of all RCTs, systematic reviews and meta-analyses on omega-3 fatty acids and psychiatric disorders without any filter or MESH restriction was performed. After eligibility processes, the final number of records included in this review was 126. One hundred and two of these studies were RCTs, while 24 were reviews and meta-analyses. The role of omega-3 fatty acids was studied in schizophrenia, major depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder (ADHD), autism spectrum disorders, eating disorders, substance use disorder and borderline personality disorder. The main evidence of the efficacy of omega-3 fatty acids has been obtained in treating depressive symptoms in patients with major depression and, to a lesser degree, bipolar depression. Some efficacy was also found in early phases of schizophrenia in addition to antipsychotic treatment, but not in the chronic phases of psychosis. Small beneficial effects of omega-3 fatty acids were observed in ADHD and positive results were reported in a few trials on core symptoms of borderline personality disorder. For other psychiatric disorders results are inconsistent.

Abstract Canine liposarcoma is an uncommon tumor that shares morphological similarities with its human counterpart. In dogs, the genetic features of this tumor are unknown and, based on immunohistochemical studies, amplification of the gene MDM2 and the mutation of TP53 are suspected. In this study 51 cases of primary liposarcomas were immunohistochemically stained for MDM2 and p53 and subjected to fluorescent in situ hybridization and next-generation sequencing to detect MDM2 amplification and TP53 mutations, respectively. MDM2 and p53 were expressed in 21 and 6 cases, respectively. MDM2 amplification and TP53 mutations were identified in 10 and 15 cases, respectively. Statistical analysis revealed an association of the myxoid subtype and the mitotic count with p53 expression and TP53 mutation. No association was found between MDM2 amplification and MDM2 expression or tumor subtype. These results suggest that despite morphological similarities, canine liposarcoma differs from its human counterpart, for which MDM2 amplification is diagnostic for well differentiated and de-differentiated variants, and TP53 mutations are more common in pleomorphic liposarcoma rather than the myxoid one as occur in our cases. Furthermore, canine myxoid liposarcoma likely represents a distinct disease rather than a mere morphological variant.