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Few longitudinal studies have so far investigated the impact of sustained COVID‐19 among people with pre‐existing psychiatric disorders. We conducted a prospective study involving people with serious mental illness (n = 114) and healthy controls (n = 41) to assess changes in the Perceived Stress Scale, Generalized Anxiety Disorder Scale, Patient Health Questionnaire, and Specific Psychotic Experiences Questionnaire scores 18 months after the COVID‐19 pandemic outset. Subjects underwent interviews with a mental health professional in April 2020 and at the end of the local third wave (October 2021). A significant increase in perceived stress was found in healthy controls, especially females. Psychiatric patients showed a significant worsening of anxiety symptoms compared to baseline records (t = −2.3, p = 0.036). Patients who rejected vaccination had significantly higher paranoia scores compared to those willing to get vaccinated (U = 649.5, z = −2.02, p = 0.04). These findings indicate that COVID‐19's sustained emergency may cause enduring consequences on mental health, soliciting further investigations. [ABSTRACT FROM AUTHOR]

Background: Clozapine is the gold standard for Treatment Resistant Schizophrenia (TRS) and its use is strongly recommended after failure of two/three antipsychotics. Nonetheless, prescribing trends do not appear to follow the global guidelines and switching to clozapine is often delayed or improper. Reasons for clozapine underuse are quite understood, whereas little is known on clozapine misuse. In fact, more stringent operative criteria to define TRS should be used in clinical practice, taking advantage of standardized assessment tools in order to avoid false TRS positive. In these perspectives, we studied the patterns of clozapine prescription in a sample of TRS and non-TRS patients, in order to identify psychopathological variables associated with lifetime exposure to clozapine. Methods: 198 consecutive patients have been screened for eligibility criteria from 2016 until 2019 at Treatment Resistant Psychosis Centre of the University of Naples “Federico II”. Only stabilized schizophrenic patients aged between 18 and 65 were enrolled. All relevant clinical-demographic data were recorded. TRS diagnosis was based on TRRIP working group operational criteria and clear pseudo-resistance factors were excluded. Patients were subdivided into two groups: those having received or currently under clozapine treatment (eCLZ) and those never treated by clozapine (nCLZ). Patients were assessed for psychotic symptoms (PANSS), cognitive performances (BACS), neurological soft signs (NES), functional capacity (UPSA), social functioning (PSP and SLOF scales), and severity of illness (CGI-S). Results: Among the patients included (92), eCLZ were 50 (54.3%), of which 20% being non-TRS. Compared to nCLZ, eCLZ had a significantly earlier age at onset, more hospitalizations, higher daily antipsychotic doses; eCLZ patients had significantly higher scores on the CGI-S, PANSS total, PANSS Negative, General Psychopathology and PAUSS subscale and, according to the Five Factor PANSS Model, higher score on Negative and Disorganization Factors; eCLZ had also more impaired Working Memory performances, higher NES Total score, lower PSP and all SLOF areas scores, except Area4. Then we use univariate and multivariate analysis to delineate predictors of clozapine exposure and to evaluate whether these factors may organize in proximal (independent) and distal (mediated) associations. We found five independently associated variables that mediate all the other ones: high antipsychotic doses, higher disease severity, suicide attempts, impaired working memory, more severe Stereotyped Thinking. Discussion: While it is expected that some TRS patients might not receive clozapine, the observation that non-TRS patients had been exposed to clozapine may surprise. A possible explanation may be the lack of systematized procedure to diagnose TRS, which is often merely coincident with a nonspecific lack of response to antipsychotics. Due to mediation analysis, we further gained insights into the hierarchy of these variables’ impact on clozapine prescription and we finally compose a complex network of proximal and distal factors predicting clozapine exposure in schizophrenic patients. The above-mentioned independent variables significantly associated with clozapine exposure let intend that eCLZ patients may belong to a subset of more severely ill ones, beyond reaching the response threshold. Earlier onset patients may suffer from a more severe disease, be more prone to suicide attempts, and less responsive to antipsychotics. This result needs to be replicated in wider samples, and this relevant therapeutic issue should be further debated in order to gather robust evidence to support or discourage clozapine off-label use and misuse. [ABSTRACT FROM AUTHOR]

Background: Earlier age at schizophrenia onset has been associated with worse prognosis, greater symptom severity, social withdrawal, poorer cognitive performances, however much heterogeneity and inconsistency in findings have been reported in these studies. Treatment Resistant Schizophrenia (TRS) is defined as the persistence of significant symptoms despite at least two adequate treatment trials, each for a minimum duration and dosage. Patients affected by TRS display worse cognitive functioning, social performances and a greater prevalence of Neurological Soft Signs compared to non-TRS. To date, no studies have explored whether early onset TRS patients differ in multiple clinical, cognitive, and social outcomes compared to early onset non-TRS patients and to adult onset patients. The objective of this study is to investigate the relationship of the condition of non-response to antipsychotic agents with age at onset of the first psychotic episode Methods: We recruited 99 non-affective psychotic patients, that were referred to our academic outpatient unit for supposed resistance to antipsychotics. The diagnosis of TRS was made by a structured diagnostic flowchart, according to published guidelines. Patients underwent a wide set of clinical and cognitive evaluations by trained raters. According to the age of the first episode of psychosis, patients were subdivided in early onset (EO, <20 years) and adult onset (AO, >20 years). Clinical and demographic variables were compared by Student’s t and Chi square tests. Then, patients were subdivided in EO-TRS, EO-nonTRS, AO-TRS, AO-nonTRS and their clinical outcomes were compared by ANCOVA, using age as a covariate. The 2way ANOVA was used to assess whether significant differences among groups were attributable to Diagnosis (TRS vs. non-TRS), Age at Onset (EO vs. AO), or combined effects. Results: Compared to AO schizophrenia patients, EO had more relevant cognitive impairments (although limited to discrete domains), more severe neurological soft signs, more severe psychotic symptoms, mostly in the disorganized and autistic trait domains, and exhibited more severe social and functional impairments. The rate of TRS patients was significantly higher in the EO group and the rate of non-TRS was significantly higher in the AO group (X=6.31, df=1, p=0.012). At the ANCOVA, EO-TRS patients had significantly longer duration of disease, more severe disease, and were under higher antipsychotic doses. Neurological soft signs were more relevant in the group of EO-TRS, while Visuospatial memory and verbal memory were more impaired in this group compared to the others. Also, this subgroup of patients exhibited the highest scores on PANSS total and subscales, and more impaired psychosocial functioning at the PSP, the UPSA, and the SLOF. Notably, in many cases, EO-TRS were more impaired than EO-nonTRS, while significant differences with AO-TRS were less consistent. 2way ANOVA demonstrated that in the majority of the investigated variables the significant differences among groups were attributable to a Diagnosis effect rather than to Age at Onset or combined effects. Discussion: The study confirmed previous observations in patients subdivided into EO vs. AO ones. However, EO patients were more frequently TRS. The group of EO-TRS had the most severe and impaired outcomes. These results were mostly dependent on the condition of nonresponse to antipsychotic agents rather than to the earlier age at onset of psychotic symptoms. The neurobiology of TRS may cause both the most severe clinical course and the earlier age at onset of these patients. Heterogeneity in previous reports on EO schizophrenia may stem from fluctuating relative rates of TRS/non-TRS patients included in some studies compared to others. [ABSTRACT FROM AUTHOR]