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Enrico Capuzzi,1 Alice Caldiroli,1 Veronica Ciscato,2 Stefania Russo,2 Massimiliano Buoli3,4 1Psychiatric Department, Azienda Socio Sanitaria Territoriale Monza, Monza, Italy; 2Department of Medicine and Surgery, University of Milano Bicocca, Monza, MB, 20900, Italy; 3Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, 20122, Italy; 4Department of Pathophysiology and Transplantation, University of Milan, Milan, ItalyCorrespondence: Massimiliano BuoliDepartment of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Via F. Sforza 35, Milan, 20122, ItalyTel +39-02-55035983Fax +39-02-55035952Email massimiliano.buoli@unimi.itAbstract: Schizophrenia remains one of the most chronic and highly disabling mental disorder. To date, the pathomechanism of schizophrenia is not fully understood and current treatments are characterized by some limitations. First- and second-generation antipsychotics have shown clinical efficacy in treating positive symptoms, while are poorly effective on both negative symptoms and cognitive deficits. Moreover, they can involve many metabolic and neurological side effects, leading to low therapeutic compliance. Many evidence suggested that serotonin may play a complex role in the neurobiology of schizophrenia. Therefore, new drugs targeting 5-HT receptors (5-HTRs) have become an important area of research in schizophrenia in the hope that treatment efficacy may be improved without inducing side effects observed with currently available antipsychotics. Research using the main database sources was conducted to obtain an overview of preclinical and clinical pharmacological 5-HTR-targeted therapies in patients with schizophrenia. We identified 17 experimental serotonergic agents, under study for their potential use in schizophrenia treatment. Particularly, AVN-211, LuAF-35700 and Brilaroxazine are currently under clinical development. Moreover, some compounds showed some pro-cognitive and antipsychotic-like properties in animal models, while other agents showed contradictory effects in improving symptoms and were removed from the development program. Although some serotonergic drugs seem promising for improving the treatment of schizophrenia, further studies regarding the pathophysiological mechanisms of schizophrenia and novel compounds as well as high-quality trials are necessary in order to improve schizophrenia outcomes.Keywords: schizophrenia, serotonin, experimental agents, negative symptoms, cognitive deficits

Aim: The aim of the present study was to identify clinical and socio‐demographic factors associated with duration of untreated illness (DUI) in patients affected by panic disorder (PD). Methods: Data were collected from patients' medical records (N = 157) of two mental health services respectively located in Milan and in Monza (Italy). Correlation analyses and analysis of variance (ANOVAs) were run to analyse the relation between DUI and quantitative/qualitative variables respectively. Statistically significant variables in uni‐ variate analyses were then inserted in a linear multivariable regression model (backward procedure). Results: Mean DUI was 27.33 (±50.56) months. Patients with an earlier age at onset (r = −0.270; p <.01), a longer duration of illness (r = 0.483; p <.01) and who received a lifetime psychotherapy (F = 6.86; p =.01) had a longer DUI. The final global model showed that a longer DUI was associated with pre‐onset poly‐substance misuse (p =.05) and a longer duration of illness (p <.01). Conclusion: The results of our study showed that a longer DUI was predicted by clinical factors such as the presence of a pre‐onset poly‐substance use disorder and that delayed proper treatment can lead to a chronicization of PD, as indicated by a longer duration of illness. Further studies are needed to in‐depth investigate the role of DUI in influencing the course and outcome of anxiety disorders, including PD. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic had a great impact on mental health, both in the general population and psychiatric patients. Little is known about the difference between these two populations in perceiving the pandemic as a traumatic event. The aim of the study was to compare psychiatric patients and healthy controls (HC) in terms of change over time of post-traumatic (PTSD) symptoms. Demographic and clinical variables were collected. Impact of Event Scale Revised (IES-R) scores were registered at T1 as lockdown period (March–April 2020) and T2 as restarting (May–June 2020). Descriptive analyses and linear regression models were performed. A total of 166 outpatients and 57 HC were recruited. Time (F = 15.76; p < 0.001) and diagnosis (F = 4.94; p < 0.001) had a significant effect on the change of IES-R scores, which resulted T1 > T2 (p < 0.001), except for subjects affected by Obsessive-Compulsive Disorder (OCD). Overall, IES-R scores were < in patients than in HC (p = 0.02), particularly in the schizophrenia (SKZ) subgroup (p < 0.001). IES-R scores of subjects with personality disorders (PDs) resulted to be > HC, although not statistically significant. The lockdown period was perceived as more traumatic than the reopening phase by both groups, with the exception of OCD patients, probably because of the clinical worsening associated with the urge of control against risks of contamination. Overall, HC reported more PTSD symptoms than psychiatric patients did, particularly SKZ ones. PD patients, in contrast, may be more vulnerable to PTSD symptoms probably as a result of poor coping skills. Together with OCD patients, subjects with PDs may need closer monitoring during the different phases of the pandemic. Trial Registration: ClinicalTrials.gov Identifier: NCT04694482 [ABSTRACT FROM AUTHOR]

Abstract Background Major depressive disorder (MDD) patients not responding to two or more different antidepressant treatments are currently considered to suffer from treatment resistant depression (TRD). Recently, intranasal esketamine has been approved by both the American Food and Drug Administration and European Medicines Agency for TRD and, more recently, in moderate to severe episode of MDD, as acute short-term treatment for the rapid reduction of depressive symptoms, which, according to clinical judgement, constitute a psychiatric emergency. There is currently no indication for obsessive–compulsive disorder (OCD) although recently published studies have already shown a rapid and significant reduction of OCD-like symptoms following ketamine administration. The etiology of OCD has not yet been fully elucidated but there is a growing evidence that glutamate signaling dysfunction in the cortico-striatal–thalamo-cortical circuitry plays an essential role. This case report exemplifies possible clinical effects of esketamine on both depressive and OCD symptoms. Case presentation We present the case of a 39-year-old man suffering from TRD. During the first evaluation at our clinic, he also reported the presence of OCD spectrum symptoms, causing him to perform time-consuming mental rituals due to pathological doubts regarding the relationship with his wife as well as intrusive thoughts regarding his mental conditions. He underwent psychometric evaluations, therapeutic drug monitoring analysis, and pharmacogenomic tests. The overall results helped to explain patient’s treatment-resistance. Moreover, we observed a significant reduction in both depressive and OCD symptoms after administration of esketamine. Conclusion This case underlines the importance of pharmacogenomic tests in profiling TRD patients and confirms the possible use of esketamine in the treatment of comorbid OCD.

B Introduction: b Past Substance Use Disorder (SUD) is frequently reported by prisoners and it is associated with an increased risk to develop psychotic symptoms during detention period [1],[2]. B Aims: b To estimate the prevalence of psychotic symptoms in a male prison population characterized by high levels of past SUD and to investigate if type of abuse, socio-demographic and clinical features may be potential risk factors for the onset of psychotic symptoms during detention. [Extracted from the article]

P.418 Are serum lipid profile and neutrophil/lymphocyte ratio associated with violent suicide attempt in patients with mental disorders? In particular, the lipid profile and inflammatory markers have been little studied in relation to aggressive-impulsive behaviour and the type of the attempted suicides among psychiatric patients, finding that lower cholesterol plasma levels may be associated to violent methods to commit suicide attempts [4]. B Aims b : To investigate whether serum lipid levels or Neutrophil/Lymphocyte Ratio (NLR) were associated with the violent method of suicide attempts in a large sample of patients with mental disorders. [Extracted from the article]

Aim : to identify relevant differences between GAD and PD in order to facilitate the differential diagnosis between the two disorders. [ABSTRACT FROM AUTHOR]

B Introduction b : The identification of biomarkers associated with psychotic symptoms can be clinically useful for the identification of patients with worse outcome. Of note, psychotic symptoms characterize not only Schizophrenia (SKZ) and Substance-induced psychotic disorder (SIPD), but also Mood Disorders [1]. Plasma levels of albumin resulted to be significantly higher in patients affected by SIPD than those affected by SKZ or psychotic/non-psychotic mood disorders (F=3.59; p=0.02). [Extracted from the article]

Introduction Schizophrenia (SKZ) is a disease characterized by positive and negative symptoms, thoughts and behaviour disorganization with a progressive socio-cognitive impairment 1 ; deficits in facial emotion recognition (FER) represent one of the most serious problems linked to interpersonal problems 2 . In addition, these patients have often comorbid condition of alcohol and substances abuse 3 . Objectives to compare the ability of FER in patients with SKZ using alcohol and/or substances (SKZ+SUD) compared to schizophrenics without SUD (SUD-SKZ). Methods we enrolled 53 subjects (M=40, F=13) with a DSM-IV diagnosis of SKZ (SCID I). The sample was divided according to alcohol and/or substance abuse (AUS and DUS) into two groups, compared for socio-demographic and clinic characteristics (PANSS and Bell model 4 ). We analyzed the association between abuse condition and Ekman test performance. Results SKZ+SUD (n=20; M=16, F=4) and SKZ-SUD (n=33; M=24, F=9) show a statistically significant age difference with a mean (SD) of 38.4 years (10.5) and 46.0 years (8.7) respectively (p=0.006). SKZ+SUD Ekman test score (mean=43.1, SD=6.9) was statistically higher (p=0.006) than SKZ-SUD (mean=34.6, SD=12.0). The different performance was more evident in comparison with poly-abusers (44.94±7.05 vs 12.04±34.6; p=0.002). We further noticed the role of disorganization as a mediator of the relationship between abuse and FER score (p=0.017): the proportion of the effect of abuse on Ekman test score was 48%. Conclusions In subjects with SKZ, FER seems to be less impaired in abusers than non-abusers. We also showed an important role of thoughts and behavioral disorganization as a mediator between SKZ+SUD and FER. [ABSTRACT FROM AUTHOR]