Clinical utility of the at-risk for psychosis state beyond transition: A multidimensional network analysis.

To be relevant to healthcare systems, the clinical high risk for psychosis (CHR-P) concept should denote a specific (i.e., unique) clinical population and provide useful information to guide the choice of intervention. The current study applied network analyses to examine the clinical specificities of CHR-P youths compared to general help-seekers and non-CHR-P youth. 146 CHR-P (mean age = 14.32 years) and 103 non-CHR-P (mean age = 12.58 years) help-seeking youth were recruited from a neuropsychiatric unit and assessed using the Structured Interview for Psychosis-Risk Syndromes, Children's Depression Inventory, Multidimensional Anxiety Scale for Children, Global Functioning: Social, Global Functioning: Role, and Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale. The first network structure comprised the entire help-seeking sample (i.e., help-seekers network), the second only CHR-P patients (i.e., CHR-P network), and the third only non-CHR-P patients (i.e., non-CHR-P network). In the help-seekers network, each variable presented at least one edge. In the CHR-P network, two isolated "archipelagos of symptoms" were identified: (a) a subgraph including functioning, anxiety, depressive, negative, disorganization, and general symptoms; and (b) a subgraph including positive symptoms and the intelligence quotient. In the non-CHR-P network, positive symptoms were negatively connected to functioning, disorganization, and negative symptoms. Positive symptoms were less connected in the CHR-P network, indicating a need for specific interventions alongside those treating comorbid disorders. The findings suggest specific clinical characteristics of CHR-P youth to guide the development of tailored interventions, thereby supporting the clinical utility of the CHR-P concept.

Defensive functioning in individuals with depressive disorders: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to address the limited generalizability of studies on defense mechanisms in depression by comparing depressive individuals with non-clinical controls (aim a) and examining changes throughout psychological interventions (aim b) (PROSPERO CRD42023442620). METHODS: We followed PRISMA 2020 guidelines, searching PubMed/Web of Science/(EBSCO)PsycINFO until 13/04/2023 for studies evaluating defense mechanisms with measures based on the hierarchical model in depressive patients versus non-clinical controls or throughout psychological intervention. We conducted random-effect meta-analyses for mature defenses/non-mature (neurotic/immature) defenses/overall defensive functioning (ODF), with standardized mean difference (SMD) as outcome measure metric. Meta-regression/sub-group/sensitivity analyses were conducted. Study quality was appraised using the Newcastle-Ottawa Scale (NOS), and certainty of evidence for aim b outcomes was evaluated using GRADE (Grading of Recommendations, Assessment, Development and Evaluations). RESULTS: 18 studies were included (mean NOS score = 5.56). Depressive patients used significantly more non-mature defenses than non-clinical controls (SMD = 0.74; k = 13). Non-clinical controls did not significantly differ in use of mature defenses compared to depressive patients (SMD = 0.33; k = 14). Significant moderators were publication year/NOS score/geographical distribution/mean age for non-mature defenses and NOS score/geographical distribution for mature defenses. Throughout psychological interventions, only ODF significantly increased (SMD = 0.55; k = 2) (GRADE = very low). LIMITATIONS: Quality of many studies was medium/sub-optimal, and longitudinal studies were scarce. CONCLUSION: Individuals with depressive disorders show a high use of non-mature defenses that could be assessed and targeted in psychological interventions, especially in younger patients.

Harmonizing early intervention strategies: scoping review of clinical high risk for psychosis and borderline personality disorder.

Aims: To map studies assessing both clinical high risk for psychosis (CHR-P) and borderline personality disorder (BPD) in clinical samples, focusing on clinical/research/preventive paradigms and proposing informed research recommendations. Methods: We conducted a PRISMA-ScR/JBI-compliant scoping review (protocol: https://osf.io/8mz7a) of primary research studies (cross-sectional/longitudinal designs) using valid measures/criteria to assess CHR-P and BPD (threshold/subthreshold) in clinical samples, reporting on CHR-P/psychotic symptoms and personality disorder(s) in the title/abstract/keywords, identified in Web of Science/PubMed/(EBSCO)PsycINFO until 23/08/2023. Results: 33 studies were included and categorized into four themes reflecting their respective clinical/research/preventive paradigm: (i) BPD as a comorbidity in CHR-P youth (k = 20), emphasizing early detection and intervention in psychosis; (ii) attenuated psychosis syndrome (APS) as a comorbidity among BPD inpatients (k = 2), with a focus on hospitalized adolescents/young adults admitted for non-psychotic mental disorders; (iii) mixed samples (k = 7), including descriptions of early intervention services and referral pathways; (iv) transdiagnostic approaches (k = 4) highlighting "clinical high at risk mental state" (CHARMS) criteria to identify a pluripotent risk state for severe mental disorders. Conclusion: The scoping review reveals diverse approaches to clinical care for CHR-P and BPD, with no unified treatment strategies. Recommendations for future research should focus on: (i) exploring referral pathways across early intervention clinics to promote timely intervention; (ii) enhancing early detection strategies in innovative settings such as emergency departments; (iii) improving mental health literacy to facilitate help-seeking behaviors; (iv) analysing comorbid disorders as complex systems to better understand and target early psychopathology; (v) investigating prospective risk for BPD; (vi) developing transdiagnostic interventions; (vii) engaging youth with lived experience of comorbidity to gain insight on their subjective experience; (viii) understanding caregiver burden to craft family-focused interventions; (ix) expanding research in underrepresented regions such as Africa and Asia, and; (x) evaluating the cost-effectiveness of early interventions to determine scalability across different countries. Systematic Review Registration: https://osf.io/8mz7a.

Patient personality and therapist responses in the psychotherapy of adolescents with depressive disorders: toward the Psychodynamic Diagnostic Manual - third edition.

Depressive disorders in adolescence pose unique challenges for assessment and treatment, particularly due to their high comorbidity with various personality disorders. Moreover, young depressed patients may elicit very intense and difficult-to-manage emotional responses in therapists (in this context, countertransference). This study aimed at empirically identifying specific personality disorders (or subtypes) among adolescents with depressive pathology and exploring distinct countertransference patterns emerging in their psychotherapy: 100 adolescents (58 with depressive disorders; 42 with other clinical conditions) were assessed by their respective clinicians (n=100) using the psychodiagnostic chart-adolescent of the Psychodynamic Diagnostic Manual (PDM) - second edition, and the therapist response questionnaire for adolescents. Results showed that depressed adolescent patients exhibited marked traits of four personality subtypes (i.e., depressive, anxious-avoidant, narcissistic, and borderline) characterized by different levels of mental functioning and personality organization. These subtypes were predictably related to specific clinicians' emotional responses, even when controlling for the intensity of depressive symptomatology. Patients with depressive or anxious-avoidant personality subtypes evoked more positive countertransference responses, whereas patients with narcissistic or borderline subtypes elicited strong and hard-to-face emotional responses in therapists. Consistent with the next edition of the PDM, the study emphasizes the importance of comprehensive psychodynamic assessment in the developmental age, which frames depressive disorders in the context of accurate emerging personality and mental functioning profiles. This approach, which also relies heavily on the clinician's subjective experience in therapy, provides crucial information on how to specifically tailor interventions that more effectively meet the needs of adolescents with these heterogeneous and complex clinical conditions.

Service users perspectives on psychosis-risk terminology: An Italian study on labeling terms preferences and stigma.

AIMS: The current range of labeling terms-at-risk mental state (ARMS), ultra-high risk for psychosis (UHR), and attenuated psychotic syndrome (APS)-used to refer to the psychosis-risk concept is varied, and their acceptability and potential stigma are not well understood. By involving Italian youth with lived experience of mental ill-health, we aimed to generate new labeling terms for psychosis-risk, and to evaluate literacy, attitudes, and preferences regarding these and the existing terms. Additionally, we investigated opinions of disclosure of the at-risk concept in clinical practice. METHODS: Through a dual-moderator focus group, novel diagnostic terms were coined for the at-risk concept: psychosis proneness (PP), change of personal reality (CPR), and hints of subjectivity dysregulation (HSD). A specifically designed questionnaire was then completed by 47 help-seeking youths, 60 relatives, and 61 clinicians to test newly generated and already established at-risk terms. RESULTS: Literacy on already established terms was significantly lower among youth (mean= 42 %) and relatives (mean= 38 %). ARMS was the preferred and least stigmatizing term among young people and clinicians. UHR was considered the most stigmatizing label. Among newly generated terms, CPR was the least stigmatizing and most informative. Disclosure of at-risk terminology was generally preferred after establishing a trusting clinician-patient relationship. CONCLUSIONS: Findings support ARMS as a useful and acceptable term in clinical practice with young people, while UHR is associated with the highest stigma. CPR is promising and should be tested in cross-cultural studies. In Italy, there is an urgent need for improving literacy on prevention in mental health.

Mental Health Literacy about Personality Disorders: A Multicultural Study.

Mental health literacy (MHL) refers to lay people's knowledge and beliefs about the diagnosis and treatment of mental illness. The current study aimed at investigating MHL regarding personality disorders (PDs) multiculturally, comparing Turkish and Italian populations. In total, 262 participants responded to an online vignette identification task that required them to label the PDs of seven hypothetical subjects and rate various dimensions of their disorders. Narcissistic (25%), obsessive-compulsive (13%), and paranoid (12%) PDs were the most correctly labeled, while the average accuracy values for other PDs were below 0.04%. Compared to Turkish participants, Italian participants were more accurate in labeling narcissistic PD. Additionally, of the seven PDs, narcissistic PD was associated with the most happiness and success at work. Subjects with borderline and avoidant PDs were the most recognized as having psychological problems (>90%), yet their PDs were among the least correctly identified. Overall, participants from both cultures were generally successful at recognizing the presence of a mental illness, but they rarely labeled it correctly. Only limited cultural differences emerged. The present findings may inform the design of outreach programs to promote MHL regarding PDs, thereby facilitating early recognition of PDs and help-seeking behaviors for affected individuals.

The Repertoire of Tissue Inhibitors of Metalloproteases: Evolution, Regulation of Extracellular Matrix Proteolysis, Engineering and Therapeutic Challenges.

Tissue inhibitors of metalloproteases (TIMPs) belong to a fascinating protein family expressed in all Metazoa. They act as regulators of the turnover of the extracellular matrix, and they are consistently involved in essential processes. Herein, we recapitulate the main activities of mammalian TIMPs (TIMP1-4) in the control of extracellular-matrix degradation and pathologies associated with aberrant proteostasis. We delineate the activity of TIMPs in the control of extracellular matrix (ECM) homeostasis and discuss the diversity of TIMPs across metazoans taking into account the emergence of the components of the ECM during evolution. Thus, the TIMP repertoire herein analysed includes the homologues from cnidarians, which are coeval with the origins of ECM components; protostomes (molluscs, arthropods and nematodes); and deuterostomes (echinoderms and vertebrates). Several questions, including the maintenance of the structure despite low sequence similarity and the strategies for TIMP engineering, shed light on the possibility to use recombinant TIMPs integrating unique features and binding selectivity for therapeutic applications in the treatment of inflammatory pathologies.

A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis.

Objective: Youths at clinical high risk for psychosis (CHR-P) are characterized by a high prevalence of anxiety and depressive disorders. The present study aimed at developing and analyzing a network structure of CHR-P symptom domains (i.e., positive, negative, disorganization, and general subclinical psychotic symptoms), depressive and anxiety symptoms, and general functioning. Methods: Network analysis was applied to data on 111 CHR-P children and adolescents (M age = 14.1), who were assessed using the Structured Interview for Prodromal Syndromes, the Children's Depression Inventory, the Children's Global Assessment Scale, and the Multidimensional Anxiety Scale for Children. Results: In the network, negative and disorganization symptoms showed the strongest association (r = 0.71), and depressive and anxiety symptoms showed dense within-domain connections, with a main bridging role played by physical symptoms of anxiety. The positive symptom cluster was not associated with any other node. The network stability coefficient (CS) was slightly below 0.25, and observed correlations observed ranged from 0.35 to 0.71. Conclusion: The lack of association between subclinical positive symptoms and other network variables confirmed the independent nature of subclinical positive symptoms from comorbid symptoms, which were found to play a central role in the analyzed network. Complex interventions should be developed to target positive and comorbid symptoms, prioritizing those with the most significant impact on functioning and the most relevance for the young individual, through a shared decision-making process. Importantly, the results suggest that negative and disorganization symptoms, as well as depressive and anxiety symptoms, may be targeted simultaneously.

Defense mechanisms in adolescents at high risk of developing psychosis: an empirical investigation.

Research within psychotherapy and psychopathology frameworks has been inspired by the central concept of defense mechanisms, which play a pivotal role in psychoanalysis. Defense specificities have only recently been studied systematically in the context of several clinical diagnoses. The present study aimed to explore the specificities of defense mechanisms in adolescents at ultra-high risk of developing psychosis and test the relationship between defensive functioning and attenuated psychotic symptoms. Twenty-six adolescent inpatients at ultra-high risk of developing psychosis and a matched clinical control group of inpatients not at risk of psychosis were interviewed. Two observer-rater methods, the Defense Mechanism Rating Scales and the Psychotic-Defense Mechanism Rating Scales were applied to interview transcripts to assess the individual use of defenses. Ultra-high-risk patients demonstrated lower defense mechanisms (i.e., total instances of defense mechanisms observed) and lower overall adaptiveness of the defenses presented. When specific differences between groups were observed, psychotic defenses were the sole defenses that could partially discriminate between ultra-high-risk and not at-risk patients. Regarding the relationship between defense mechanisms and subthreshold psychotic symptoms, psychotic defenses were associated with negative and disorganization symptoms, rather than with positive symptoms. The psychological vulnerability of ultra-high-risk patients is discussed and treatment implications for psychotherapy with such challenging patients are addressed.