Is depressed mood clinically relevant at the onset of schizophrenia? A longitudinal study.

Aim: Depressed mood (DM) in schizophrenia is often associated with suicide risk and poor outcomes. However, it is generally overlooked in clinical practice, especially in First Episode Schizophrenia (FES). The aims of this investigation were: (1) to calculate baseline prevalence of FES patients with relevant DM, (2) to longitudinally monitor DM severity levels over a 12-month follow-up, and (3) to investigate their associations with clinical data and the specific treatment components of an “Early Intervention in Psychosis” (EIP) program. Material and Methods: The Positive and Negative Syndrome Scale (PANSS) was completed by all FES participant. Individuals with a baseline PANSS “Depression” item subscore of ≥ 5 were classified as having relevant depressed mood (FES/DM+). Chi-square and Mann-Whitney tests were used for inter-group comparisons. A linear regression analysis was also performed. Results: Fifty-three (33.3%) participants were in the FES/DM+ subgroup. Relevant DM at baseline was associated with female gender and a higher PANSS “Positive Symptoms” score. Across the follow-up, FES individuals improved their DM severity levels. This was significantly related to a longitudinal decrease in PANSS “Positive Symptoms” levels. Conclusions: DM is relatively frequent in FES, already at the recruitment in EIP services. However, its severity decreases overtime within specialized EIP programs

DEPRESSIVE FEATURES IN INDIVIDUALS WITH FIRST EPISODE PSYCHOSIS: PSYCHOPATHOLOGICAL AND TREATMENT CONSIDERATIONS FROM A 2-YEAR FOLLOW-UP STUDY

Objective: Comorbid depression is quite common in early psychosis and specifically related to suicidal behavior and poor long-term outcomes. However, Depressive Symptoms (DS) are often neglected in both research and treatment, especially at the psychosis onset. The goals of this investigation were: (a) to longitudinally explore DS levels in patients with First Episode Psychosis (FEP) during 24 months of follow-up, and (b) to investigate the associations of DS with psychopathology and intervention components of an “Early Intervention in Psychosis” (EIP) program across the follow-up period. Method: The Global Assessment of Functioning (GAF) and the Positive And Negative Syndrome Scale (PANSS) were completed by 266 FEP subjects. A linear regression analysis with DS as the dependent parameter and psychopathological and treatment characteristics as independent variables was performed (both at baseline and across the follow-up period). Results: DS had enduring associations with PANSS “Positive Symptoms” and “Negative Symptoms” subscores. During the investigation, FEP subjects significantly improved their DS severity levels. This was related to the number of individual psychotherapy meetings supplied within the EIP protocol, as well as to a higher antidepressant dose and a lower antipsychotic dose prescribed during the follow-up. Conclusions: DS are quite prominent in FEP, even at the recruitment time in EIP services. Nevertheless, DS severity tends to diminish overtime, especially with the provision of specialized EIP treatments

Short‑term disengagement from early intervention service for first‑episode psychosis: findings from the “Parma Early Psychosis” program.

tors of engagement is crucial to maximize mental healthcare interventions in first-episode psychosis (FEP). No Italian study on this topic has been reported to date. Thus, the aims of this investigation were: (1) to examine short-term disengagement rate in an Italian population of FEP patients treated within an EIP service across a 1-year follow-up period, and (b) to assess the most relevant predictors of disengagement in the first year of treatment. Methods All participants were young FEP help-seeking patients, aged 12–35 years, enrolled within the “Parma Early Psychosis” (Pr-EP) protocol. At baseline, they completed the Positive And Negative Syndrome Scale (PANSS), the Health of the Nation Outcome Scale (HoNOS) and the Global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were used. Results 496 FEP individuals were enrolled in this research. Across the follow-up, a 16.5% prevalence of short-term disengagement was found. Particularly robust predictors of service disengagement were poor baseline treatment non-adherence, living with parents and the presence of brief psychotic disorder or schizophreniform disorder at entry. Conclusion About 16% of FEP patients disengaged the Pr-EP program within the first year of treatment. A solution to reduce disengagement and/or to favor re-engagement of these subjects might be to remain on EIP program caseloads allowing the option for low-intensity support and monitoring, also via remote technology

Tankyrase inhibition impairs directional migration and invasion of lung cancer cells by affecting microtubule dynamics and polarity signals

Raw data for Fig. S2. (XLSX 48 kb

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway(1,2). Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability. The autophagic tumour-suppressor protein AMBRA1 has been linked to the control of cell proliferation, but the underlying molecular mechanisms remain poorly understood. Here we show that AMBRA1 is an upstream master regulator of the transition from G1 to S phase and thereby prevents replication stress. Using a combination of cell and molecular approaches and in vivo models, we reveal that AMBRA1 regulates the abundance of D-type cyclins by mediating their degradation. Furthermore, by controlling the transition from G1 to S phase, AMBRA1 helps to maintain genomic integrity during DNA replication, which counteracts developmental abnormalities and tumour growth. Finally, we identify the CHK1 kinase as a potential therapeutic target in AMBRA1-deficient tumours. These results advance our understanding of the control of replication-phase entry and genomic integrity, and identify the AMBRA1-cyclin D pathway as a crucial cell-cycle-regulatory mechanism that is deeply interconnected with genomic stability in embryonic development and tumorigenesis

Rates and predictors of service disengagement in adolescents with first episode psychosis: results from the 2‐year follow‐up of the Pr‐EP program.

Service disengagement is a major concern for “Early Intervention in Psychosis” (EIP). Indeed, understanding predictors of engagement is important for the efectiveness of mental health interventions, to improve outcome and quality of life, also in adolescents with frst episode psychosis (FEP). No specifc European investigation on this topic in adolescence has been reported in the literature to date. The aim of this study was to investigate service disengagement rate and predictors in an Italian sample of FEP adolescents treated within an EIP program during a 2-year follow-up period. All participants were adolescents help-seekers (aged 12–18 years) enrolled in the “Parma Early Psychosis” (Pr-EP) program. At baseline, they completed the Positive and Negative Syndrome Scale (PANSS) and the global Assessment of Functioning (GAF) scale. Univariate and multivariate Cox regression analyses were performed. 71 FEP adolescents were recruited in this research. During the 2 years of our follow-up, a 25.4% prevalence rate of service disengagement was found. Particularly robust predictors of disengagement were lower baseline acceptance of psychosocial interventions, substance abuse at entry, and lower baseline PANSS “Disorganization” factor score. Approximately, 1/4 of our FEP adolescents disengaged from the Pr-EP program during the frst 2 years of treatment. A possible solution to decrease disengagement and to favor re-engagement of these young individuals might be to provide the option of low-intensity monitoring and support, also via remote technology

Kinesin-2 Controls the Motility of RAB5 Endosomes and Their Association with the Spindle in Mitosis

RAB5 is a small GTPase that belongs to the wide family of Rab proteins and localizes on early endosomes. In its active GTP-bound form, RAB5 recruits downstream effectors that, in turn, are responsible for distinct aspects of early endosome function, including their movement along microtubules. We previously reported that, at the onset of mitosis, RAB5positive vesicles cluster around the spindle poles and, during metaphase, move along spindle microtubules. RNAi-mediated depletion of the three RAB5 isoforms delays nuclear envelope breakdown at prophase and severely affects chromosome alignment and segregation. Here we show that depletion of the Kinesin-2 motor complex impairs long-range movement of RAB5 endosomes in interphase cells and prevents localization of these vesicles at the spindle during metaphase. Similarly to the effect caused by RAB5 depletion, functional ablation of Kinesin-2 delays nuclear envelope breakdown resulting in prolonged prophase. Altogether these findings suggest that endosomal transport at the onset of mitosis is required to control timing of nuclear envelope breakdown