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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.

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.

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.

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 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.