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Suicide is a relevant worldwide public health problem. Many studies have shown that different demographic and clinical factors are potentially associated with suicidal behavior. Other studies have reported data about the role of biomarkers in the onset of suicidal behaviors. Specifically, researchers have found that suicidal risk may be increased by abnormalities in serotonergic system, hypothalamic-pituitary-adrenal axis, lipid metabolism, immune system and neuronal plasticity. The identification of specific biological parameters associated with self-harm may be helpful to implement prevention strategies and also to detect new therapeutic strategies. In this review, we summarize and analyze the results of main studies about neurobiological mechanisms related to suicidal behavior, also exploring the possible interconnection between the different biological systems.

We read with interest the paper by Fovet and colleagues1 wherein the authors conducted a cross sectional survey to estimate prevalence rates of psychiatric disorders (PDs) and substance use disorders (SUDs) in 622 (599 men and 23 women) randomly selected inmates who had recently been committed to the French general population prison system in the north of France. The Mini International Neuropsychiatric Interview was used as screening program. The prevalence rates of PDs and SUDs among newly arrived prisoners were compared with a sample of subjects representative of general population. The findings are interesting and show that nearly two third of the newly incarcerated people had at least one PDs or SUDs. Noteworthy, 41.6% of newly admitted inmates had two or more psychiatric comorbidities. Moreover, more than 30% of the sample had a suicide risk while 6.9% had any psychotic syndrome (isolated or recurrent). Apart from dysthymia and current isolated psychotic syndrome, the prevalence rates of PDs and SUDs were significantly higher in prison sample than in general population, matched on age and sex. These results did not surprise us. We conducted a cross-sectional study including a sample of 141 male prisoners, admitted to Monza detention centre between January 2017 and March 2019. Subjects eligible for this study were aged between 18 and 65 years, suffering from any SUD but not reporting a previous diagnosis of “psychosis” or “schizophrenia” or taking antipsychotics. The Brief Psychiatric Rating Scale was administered to assess the presence of positive psychotic symptoms. Forty-five of them (31.9%) presented psychotic symptoms. We found that those with a history of previous incarceration (aOR=3.27, p=0.02) and suicide attempts inside (aOR=12.13, p=0.004) or outside prison (aOR=4.57, p=0.003) had significantly increased the likelihood of psychotic symptoms. Moreover, we found that psychotic subjects reported more frequently substance misuse than the counterpart (aOR=1.61, p=0.03). These results have been achieved comparing psychotic and non-psychotic inmates through multivariate logistic regression analyses using as covariates age, age at first imprisonment and age of onset of SUD (Table 1) . Table 1 about here The combined interpretation of our results with those of Fovet's study emphasises that several subjects both at risk of psychotic disorders and criminal behavior may not be fully detected by outpatient mental health services. This aspect is of current interest because inmates with an undiagnosed or untreated psychotic disorder potentially have a worse outcome than healthy ones2. Indeed, we found that people with psychotic symptoms were potentially at high risk of criminal involvement, since more frequently incarcerated. Moreover, our study shows that psychotic symptoms are significantly related to increasing risk of suicide attempt, both inside and outside of prison, although we cannot entirely exclude that multiple incarcerations might be a confounder. This result is in line with previous findings suggesting that prisoners may have high rates of suicide attempt not merely within prison, but also after release, particularly in the first months3. Nevertheless, inmates with dual diagnosis may be at increased risk of resumption of difference substances after release, which in turn may rise the risk of both overdose death and psychotic disorders. In this regard, we found that poly-abuse may be associated with the presence of psychotic symptoms. Although the measure of psychotic symptoms was restricted to four items of The Brief Psychiatric Rating Scale, our study shows that psychotic offenders should be considered a fragile population. Therefore, as reported by Fovet and colleagues, the detection of psychiatric and SUDs on admission to prison facilities should be promoted in order to initiate adequate treatment. Nevertheless, an appropriate community-based treatment after the release from prison is definitely an important part of the management of these patients to reach a successful reintegration and to avoid post-release mortality4. Finally, mental healthcare access should be promoted among disadvantaged areas as well as novel integrated treatments for patients with a dual diagnosis should be introduced and implemented5

Introduction: In most countries the percentage of repeat offenders has been increasing1. Many factors, including family background, education, occurrence of mental illness with, especially, substance use disorder, may predict the recidivism2. Moreover childhood maltreatment increases the risk of repeat offence and, among specific types of victimization, neglect might be a strong predictor of recidivism3. Objectives: To examine associations among childhood victimization and criminal recidivism Methods: We enrolled 215 male inmates. Recidivism was defined as the occurrence of one or multiple new convictions for any kind of offense. So the sample was divided, according to presence of recidivism, into two groups, compared for sociodemographic and clinic characteristics. History of childhood victimization was assessed with the Childhood Trauma Questionnaire Short Form (CTQ-SF) 4. The presence of specific trauma (emotional, physical and sexual abuse; emotional and physical neglect) was determined by meeting a threshold of moderate maltreatment severity 5 . Results: At univariate analyses, subjects with (n=124) and without recidivism (n=91) exhibited a statistically significant association in the scores of physical neglet (p=0.00) and abuse (p=0.03). However, logistic regression analyses showed that only physical neglet was associated with recidivism (OR:2.32, 95% CI: 1.03-5.21). Moreover lower education, dual diagnosis and gambling were related to an increasing likelihood of criminal recidivism (table 1). Conclusions: Childhood maltreatment is associated with recidivism. In particular, physical neglect during childhood plays a critical role in repeated crime, in relationship with mental, substance use disorders and pathologic gambling. A careful evaluation of childhood maltreatment in the assessment and treatment of criminal offenders could be needed.

Anorexia Nervosa (AN) is a disabling disorder characterized by extreme weight loss and frequent chronicization, especially in its most severe forms. This condition is associated with a pro-inflammatory state; however, the role of immunity in symptom severity remains unclear. Total cholesterol, white blood cells, neutrophils, lymphocytes, platelets, iron, folate, vitamin D and B12 were dosed in 84 female AN outpatients. Mildly severe (Body Mass Index—BMI ≥ 17) versus severe (BMI < 17) patients were compared using one-way ANOVAs or χ2 tests. A binary logistic regression model was run to investigate the potential association between demographic/clinical variables or biochemical markers and the severity of AN. Patients with severe anorexia (compared to mild forms) were older (F = 5.33; p = 0.02), engaged in more frequent substance misuse (χ2 = 3.75; OR = 3.86; p = 0.05) and had a lower NLR (F = 4.12; p = 0.05). Only a lower NLR was predictive of severe manifestations of AN (OR = 0.007; p = 0.031). Overall, our study suggests that immune alterations may be predictive of AN severity. In more severe forms of AN, the response of the adaptive immunity is preserved, while the activation of the innate immunity may be reduced. Further studies with larger samples and a wider panel of biochemical markers are needed to confirm the present results.

Treatment discontinuation is a major challenge in routine clinical settings. Despite poor adherence to antipsychotic medication, long acting injectable (LAI) formulations are an underutilized option in psychotic disorders. Recently, an earlier and broader use of LAIs has been emphasized. However, few studies have evaluated the factors associated with LAI antipsychotic discontinuation in ordinary clinical practice. The main purpose of the present study was, therefore, to identify the factors associated with LAI discontinuation in a real-world setting. Patients in treatment with LAI antipsychotics were recruited. A Cox regression analysis was applied considering a 12-month follow-up period. Moreover, a Kaplan-Meier survival analysis was applied to compare the single treatment LAI antipsychotic groups in terms of time to discontinuation. Our analysis showed an LAI discontinuation rate at 12 months, corresponding to 28.8%, with olanzapine and aripiprazole having a longer time to discontinuation compared to zuclopenthixol. The results of the present study can help clinicians with their choice of LAI antipsychotic according to patients’ characteristics and in a context of precision medicine. Increasing knowledge about factors affecting discontinuation of LAI antipsychotics can improve the prescribing practices of these compounds. Individualized approaches may ameliorate long-term patients’ treatment adherence, thus preventing the long-term disability caused by psychotic disorders.

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 T2 (p 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.

Generalized Anxiety Disorder (GAD) and Panic Disorder (PD) share underlying neurobiological mechanisms and several clinical features which, with medical comorbidities, may increase misdiagnosis and delay proper treatment. The aim of the study was to evaluate the association between clinical/socio-demographic markers and GAD/PD diagnosis. Outpatients (N = 290) with PD or GAD were identified in mental health services in Monza and Milan (Italy). Descriptive analyses and a binary logistic regression model were performed. Post-onset psychiatric (p = 0.05) and medical (p = 0.02) multiple co-morbidities were associated with GAD; treatment with selective serotonin reuptake inhibitors (SSRIs) was associated with PD, while GAD diagnosis was associated with treatment with atypical antipsychotics or GABAergic drugs (p = 0.03), as well as psychodynamic psychotherapy (p < 0.01). Discontinuation of the last pharmacological treatment was associated with GAD diagnosis rather than the PD one (p = 0.02). GAD patients may have a worse prognosis than PD patients because of more frequent multiple co-morbidities, relapses and poorer treatment compliance. The different treatment approaches were consistent with the available literature, while the association between GAD and psychodynamic psychotherapy is an original finding of our study. Further studies on larger samples are necessary to better characterize clinical factors associated with GAD or PD.

Introduction: Social anxiety disorder (SAD) is associated with scarce functioning and poor quality of life. Although selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) are currently first-line treatments, side effects are common and affect treatment compliance in approximately 50% of patients. This review aimed to summarize data on the efficacy of unlabeled molecules for SAD treatment. Areas covered: Research in the main psychiatric databases was conducted (PubMed, PsychINFO, and EMBASE-Ovid) to select studies investigating the efficacy of marketed molecules not labeled for SAD treatment. Expert opinion: Pregabalin at high doses (450–600 mg/day) appears to be a reliable alternative strategy for SAD treatment. Among the SSRIs not labeled for SAD, citalopram showed the most promising results. Quetiapine, levetiracetam, and other antidepressants/serotonergic agents, such as fluoxetine, duloxetine, monoamine oxidase inhibitors, tricyclics, mirtazapine, atomoxetine, nefazodone, vilazodone, and buspirone, presented negative, limited, or contrasting results. Data on anticonvulsants, olanzapine, tiagabine, and ketamine were positive, but preliminary. The risk/benefit ratio must be considered in the prescription of unlabeled compounds; treatment with pregabalin may be associated with somnolence and dizziness. Future research may contribute to the identification of targeted molecules for the treatment of this disorder.

Introduction: Bipolar Disorder (BD) is a disabling condition with suicidal behavior as one of the most common adverse outcomes. The purpose of the present research is to investigate the relationship between lifetime suicide attempts and the clinical factors/biochemical parameters in a large sample of bipolar patients. Methods: A total of 561 patients, consecutively hospitalized for BD in Milan and Monza (Italy), were recruited. Data about the demographic and clinical variables, as well as the values of blood analyses, were collected. The groups identified according to the presence/absence of lifetime suicide attempts were compared using univariate analyses. Then, three preliminary binary logistic regressions and a final logistic regression model were performed to identify the clinical and biochemical parameters associated with lifetime suicide attempts in BD. Results: Lifetime suicide attempts in BD were predicted by a longer duration of untreated illness (DUI) (p = 0.005), absence of lifetime psychotic symptoms (p = 0.025), presence of poly-substance use disorders (p = 0.033), comorbidity with obesity (p = 0.022), a last mood episode of manic polarity (p = 0.044), and lower bilirubin serum levels (p = 0.002); higher total cholesterol serum levels showed a trend toward statistical significance (p = 0.058). Conclusions: BD patients with lifetime suicide attempts present unfavorable clinical features. Some specific biochemical characteristics of bipolar patients may represent potential markers of suicidal behavior and need to be better investigated to identify new targets of treatment in the framework of personalized medicine. These preliminary findings have to be confirmed by further studies in different clinical settings.

Background: The aim of the present study was to summarise the available data about the link between air pollution exposure and the new-onset and severity of psychiatric disorders in pregnant women during the perinatal period. Materials and methods: We selected articles published until June 2022 on PubMed and the Web of Science. Pollutants included were PM2.5 (particulate matter 2.5 micrometres and smaller), PM10 (particulate matter 10 micrometres and smaller), NO2 (nitrogen dioxide), O3 (ozone), SO2 (sulphur dioxide), CO (carbon monoxide), PBDEs (polybrominated diphenyl ethers), PFAS (per- and polyfluoroalkyl substances), lead, and cadmium. The perinatal period was considered as the time of pregnancy until one year after childbirth. Results: Nine studies were included; most of them evaluated the association between exposure to air pollutants and the onset of Postpartum Depression (PPD). Two studies showed an association between, respectively, only PM2.5 and both PM2.5 and NO2 exposure and PPD onset 12 months after childbirth, while another study found a significant association between NO2 exposure and PPD occurrence 6 months after childbirth. PBDE blood levels were associated with more severe depressive symptoms. Lastly, one study observed a link between stressful symptoms and exposure to PM2.5, PM10 during pregnancy. Conclusion: More comprehensive and uniform studies are required to make a roadmap for future interventions, given the growing relevance of issues such pollution and mental health, particularly during the perinatal period.

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

BackgroundSuicidality is one of the most common complications of mental disorders, so that the identification of potential biomarkers may be relevant in clinical practice. To date, the role of serum lipids and neutrophil/lymphocyte ratio (NLR) has been explored albeit with conflicting results. To the best of our knowledge, no study has explored lipid levels concomitantly with NLR in relation to violent suicide attempts. Therefore, we aimed to investigate whether serum lipid levels and NLR might be associated with the violent method of suicide attempts.MethodsThe study group consisted of 163 inpatients who attempted suicide. Blood samples were collected at the beginning of hospitalization to measure total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein, very-low-density lipoprotein (VLDL), triglycerides, and NLR. Descriptive analyses of the total sample were performed. The included patients were divided into two groups according to violent/nonviolent method. Groups were compared in terms of lipid (MANCOVAs).ResultsPlasma levels of total cholesterol (F = 5.66; P = .02), LDL (F = 4.94; P = .03), VLDL (F = 5.66; P = .02), and NLR (F = 8.17; P ConclusionsLow cholesterol, LDL, and VLDL levels as well as low NLR value were associated with a violent method of suicide attempt in patients with mental disorders. Further studies are needed to confirm these results.

Malondialdehyde (MDA) represents one of the final products of lipid peroxidation that is thought to be enhanced and accelerated in patients affected by bipolar disorder (BD). Purpose of the present article is to critically summarize the available data about MDA as a candidate biomarker for BD. First, we carried out a systematic review of the literature selecting those papers that evaluated MDA levels in BD. Then, we performed two separate meta-analyses: one of the studies that compared healthy controls (HC) with unmedicated BD and one with the studies that assessed MDA levels before and after treatment in BD, showing that bipolar patients experience more oxidative stress than healthy subjects and that treatment is effective in reducing MDA levels. In the first set of studies, we also explored through a meta-regression whether age, gender and experiencing an episode specifically influenced the difference between BD and HC in MDA levels. Bipolar patients compared to healthy subjects had higher MDA levels (SMD: 0.94, 95% CI: 0.23-1.64). Age (p < 0.01), gender (p < 0.01) and the presence of a current mood episode (p < 0.01) significantly influenced MDA plasma/serum levels. Specifically, studies that included more female, older subjects and more BD in euthymia were more likely to have higher MDA levels. Finally, patients after treatment had lower levels of MDA compared to baseline (SMD: -0.52, 95% CI: -0.85 -0.19). More studies are needed to draw definitive conclusions.

Antisocial Personality Disorder (APD) is a condition largely represented in detention centers where can reach a prevalence of 60% in male prisoners. The objective of this study is to identify the clinical and demographic factors that differentiate subjects with APD and hosted in penitentiary with respect to those are treated in outpatient psychiatric clinics. We recruited 65 male patients affected by APD, whose 26 were followed up in community mental health services and 39 were serving their sentence in a detention center located in Monza. Socio-demographic and clinical data were obtained through a review of the clinical charts, and interviews with patients or their relatives (if available). We performed descriptive analyses on the total sample, then we compared the two groups identified by the type of setting (outpatient clinic vs. penitentiary) by independent sample t tests (quantitative variables) or χ2 tests (qualitative ones). For qualitative variables odds ratios ( ORs) were also calculated. Outpatients with APD (with respect to those hosted in the detention center) resulted: to be older ( p = .02), to be less likely married ( p = .01), to have more pre-onset psychiatric comorbidity ( p = .05), to have more pre-onset substance poly-misuse ( p = .01), to have more previous psychiatric hospitalizations ( p < .01), and to be less likely to have received lifetime psychotherapy ( p < .01). Globally, the results of this study show how the presence of psychiatric comorbidity or substance abuse (with the probable access to psychiatric services) before the onset of APD prevents imprisonment. This aspect is even more surprising when we consider that the two groups of patients show no differences in the frequency of crimes. Future research will have to confirm if early mental health care can really limit the access to penitentiary of subjects affected by APD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent condition with onset in childhood and in many cases persisting into adulthood. Even though an increasing number of studies have investigated the efficacy of pharmacotherapy in the management of adult ADHD, few authors have tried to identify the biological predictors of treatment response. Objectives: To summarize the available data about the biological markers of treatment response in adults affected by ADHD. Methods: A search on the main biomedical and psychological archives (PubMed, Embase, Scopus, and PsycINFO) was performed. Manuscripts in English, published up to May 2022 and having the biological predictors of treatment response in adults with ADHD as their main topic, were included. Results: A total of 3855 articles was screened. Twenty-two articles were finally included. Most of the manuscripts studied neuroimaging and electrophysiological factors as potential predictors of treatment response in adult ADHD patients. No reliable markers were identified until now. Promising findings on this topic regard genetic polymorphisms in snap receptor (SNARE) proteins and default mode network-striatum connectivity. Conclusions: Even though some biological markers seem promising for the prediction of treatment response in adults affected by ADHD, further studies are needed to confirm the available data in the context of precision medicine.

SARS-CoV-2 infection causes a pulmonary disease (COVID-19) which spread worldwide generating fear, anxiety, depression in the general population as well as among subjects affected by mental disorders. Little is known about which different psychopathological changes the pandemic caused among individuals affected by different psychiatric disorders, which represents the aim of the present study. Specific psychometric scales were administered at three time points: T0 as outbreak of pandemic, T1 as lockdown period, T2 as reopening. Descriptive analyses and linear regression models were performed. A total of 166 outpatients were included. Overall, psychometric scores showed a significant worsening at T1 with a mild improvement at T2. Only psychopathology in schizophrenia (SKZ) patients and obsessive-compulsive (OC) symptoms did not significantly improve at T2. Subjects affected by personality disorders (PDs) resulted to be more compromised in terms of general psychopathology than depressed and anxiety/OC ones, and showed more severe anxiety symptoms than SKZ patients. In conclusion, subjects affected by PDs require specific clinical attention during COVID-19 pandemic. Moreover, the worsening of SKZ and OC symptoms should be strictly monitored by clinicians, as these aspects did not improve with the end of lockdown measures. Further studies on larger samples are needed to confirm our results. ClinicalTrials.gov Identifier: NCT04694482.

Social anxiety disorder (SAD) is a common psychiatric condition associated with a high risk of psychiatric comorbidity and impaired social/occupational functioning when not promptly treated. The identification of biological markers may facilitate the diagnostic process, leading to an early and proper treatment. Our aim was to systematically review the available literature about potential biomarkers for SAD. A search in the main online repositories (PubMed, ISI Web of Knowledge, PsychInfo, etc.) was performed. Of the 662 records screened, 61 were included. Results concerning cortisol, neuropeptides and inflammatory/immunological/neurotrophic markers remain inconsistent. Preliminary evidence emerged about the role of chromosome 16 and the endomannosidase gene, as well as of epigenetic factors, in increasing vulnerability to SAD. Neuroimaging findings revealed an altered connectivity of different cerebral areas in SAD patients and amygdala activation under social threat. Some parameters such as salivary alpha amylase levels, changes in antioxidant defenses, increased gaze avoidance and QT dispersion seem to be associated with SAD and may represent promising biomarkers of this condition. However, the preliminary positive correlations have been poorly replicated. Further studies on larger samples and investigating the same biomarkers are needed to identify more specific biological markers for SAD.

Treatment resistant depression (TRD) is associated with poor outcomes, but a consensus is lacking in the literature regarding which compound represents the best pharmacological augmentation strategy to antidepressants (AD). In the present review, we identify the available literature regarding the pharmacological augmentation to AD in TRD. Research in the main psychiatric databases was performed (PubMed, ISI Web of Knowledge, PsychInfo). Only original articles in English with the main topic being pharmacological augmentation in TRD and presenting a precise definition of TRD were included. Aripiprazole and lithium were the most investigated molecules, and aripiprazole presented the strongest evidence of efficacy. Moreover, olanzapine, quetiapine, cariprazine, risperidone, and ziprasidone showed positive results but to a lesser extent. Brexpiprazole and intranasal esketamine need further study in real-world practice. Intravenous ketamine presented an evincible AD effect in the short-term. The efficacy of adjunctive ADs, antiepileptic drugs, psychostimulants, pramipexole, ropinirole, acetyl-salicylic acid, metyrapone, reserpine, testosterone, T3/T4, naltrexone, SAMe, and zinc cannot be precisely estimated in light of the limited available data. Studies on lamotrigine and pindolol reported negative results. According to our results, aripiprazole and lithium may be considered by clinicians as potential effective augmentative strategies in TRD, although the data regarding lithium are somewhat controversial. Reliable conclusions about the other molecules cannot be drawn. Further controlled comparative studies, standardized in terms of design, doses, and duration of the augmentative treatments, are needed to formulate definitive conclusions.

Major Depressive Disorder (MDD) is a medical illness twice as common in women than in men lifetime. Purpose of this study is to identify gender differences in clinical and biochemical parameters in subjects affected by MDD to implement individualized treatment strategies. We recruited 234 patients (112 males and 122 females) consecutively hospitalized for MDD in Milan (Italy). Data were obtained through a screening of the clinical charts and blood analyses. Univariate analyses, binary logistic regressions and a final logistic regression model were performed. The final logistic regression model showed that female patients (compared to males) had lower plasmatic levels of hemoglobin (p = 0.020) and uric acid (p = 0.002), higher levels of cholesterol (p < 0.001), had been treated with a lower number of antidepressants (p = 0.011), presented lower red blood cells (p < 0.001) and showed more frequently comorbidity with hypothyroidism (p = 0.036). Univariate analyses identified also that women had an earlier age at onset (p = 0.043), were less likely to have comorbidity with diabetes (p = 0.002) and were less frequently treated with a psychiatric polytherapy (p < 0.001). Finally, female patients had achieved more frequently remission in the last depressive episode (p = 0.001) and were more likely to have family history for psychiatric disorders (p < 0.001) than males. Female patients globally have a better response to treatments, but they seem to be more vulnerable to specific metabolic abnormalities as showed by more frequent hypercholesterolemia and lower plasma levels of uric acid. These results have to be confirmed by further studies.

The advent of intra-nasal esketamine (ESK), one of the first so called fast-acting antidepressant, promises to revolutionize the management of treatment resistant depression (TRD). This NMDA receptor antagonist has proven to be rapidly effective in the short- and medium-term course of the illness, revealing its potential in targeting response in TRD. Although many TRD ESK responders are able to achieve remission, a considerable portion of them undergo a metamorphosis of their depression into different clinical presentations, characterized by instable responses and high recurrence rates that can be considered closer to the concept of Difficult to Treat Depression (DTD) than to TRD. The management of these DTD patients usually requires a further complex multidisciplinary approach and can benefit from the valuable contribution of new personalized medicine tools such as therapeutic drug monitoring and pharmacogenetics. Despite this, these patients usually come with long and complex previous treatments history and, often, advanced and sophisticated ongoing pharmacological schemes that can make the finding of new alternative options to face the current recurrences extremely challenging. In this paper, we describe two DTD patients—already receiving intranasal ESK but showing an instable course—who were clinically stabilized by the association with minocycline, a semisynthetic second-generation tetracycline with known and promising antidepressant properties.

Atypical antipsychotic depot medications are currently recommended for patients with schizophrenia (SCZ) to prevent relapse and ameliorate the long-term prognosis of these patients. This review critically summarizes the available data about the association between the plasma concentrations of long-acting Second- Generation Antipsychotics (SGAs) and the clinical effectiveness of these compounds in patients affected by SCZ or schizoaffective disorder. Our question is if the measurement of these concentrations can be helpful for clinicians in predicting treatment response and clinical stabilization of patients. Bibliographic research on the main databases was performed, and 13 studies were finally included in this review. Contrasting results were found between plasma concentrations of long-acting injectable (LAI) risperidone and clinical amelioration according to rating scale scores. Data are too scanty to draw conclusions for olanzapine and paliperidone. In contrast, despite small sample sizes, data are quite concordant in showing a relation between long-acting SGA plasma concentrations and D2 receptor occupancy. Despite the preliminary encouraging results, particularly for D2 receptor occupancy, future research with larger samples will have to confirm the clinical usefulness of measuring LAI SGA plasma concentrations to predict the clinical response of patients affected by severe mental conditions such as SCZ.

Background Prisoners have higher rates of suicide attempts compared with general population. A history of childhood trauma (CT) is common among incarcerated subjects and it is a well-known risk factor for lifetime suicide attempts. Therefore, the purpose of the study was to investigate whether lifetime suicide attempts may be related to the exposition to CT among male prisoners. Method We conducted a cross sectional study recruiting newly arrived inmates in an Italian jail, between January 2017 and June 2018. Prisoners were interviewed to collect socio-demographic and clinical information. Moreover, inmates completed the Childhood Trauma Questionnaire. We excluded prisoners unable to speak or read Italian, with learning disabilities or current severe psychiatric symptoms. Results A total of 215 consecutive male inmates were included. Fifty-one prisoners (23.7%) had a history of attempted suicide. The most reported CT was physical neglect. Multivariate logistic regression analysis showed that a history of childhood sexual abuse, emotional neglect and psychiatric diagnosis significantly increased the likelihood of lifetime suicide attempt. Conclusions A previous history of suicide attempt is highly prevalent among inmates. In agreement with previous findings, lifetime suicide attempts seem to be associated with the presence of CT and psychiatric diagnosis. Therefore, CT should be considered as a relevant variable to improve the programs for the prevention of suicide in prison.

OBJECTIVE: To assess the long-term impact of early COVID-19 lockdown phase on emergency psychiatric consultations in two psychiatric emergency departments located in Italy. METHODS: We conducted a cross-sectional study comparing the number and characteristics of emergency psychiatric consultations during post-lockdown with respect to the lockdown period. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis, information on multiple psychiatric consultations and hospitalisation were collected. RESULTS: A rise of almost 60% in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed. Emergency psychiatric consultations in the post-lockdown period were associated with lower rates of cannabis (aOR = 0.42, p = 0.011) and cocaine use (aOR = 0.39, p = 0.011). Despite a lower occurrence of two or more psychiatric consultations was observed during post-lockdown phase (aOR = 0.44, p = 0.008), subjects who had anxiety disorders (aOR = 3.91, p = 0.000) and substance intoxication or withdrawal (aOR = 6.89, p = 0.000) were more likely to present to emergency psychiatric consultations during post-lockdown period compared to the lockdown one. CONCLUSIONS: Substance intoxication or withdrawal and anxiety disorders increased after the COVID-19 lockdown. The findings of this study suggest to address more economic and professional sources to the mental health areas potentially more affected by the different phases of a pandemic.KEYPOINTSCOVID-19 pandemic and lockdown measures increased mental health unmet needs.According to our findings, a rise in emergency psychiatric consultations during the post-lockdown compared to the lockdown period was observed.Patients with substance intoxication or withdrawal syndrome and anxiety disorders were significantly more likely to present to emergency psychiatric consultations during post-lockdown.Lockdown was associated with higher rates of both cannabis and cocaine use disorders as well as of multiple psychiatric consultations.Alternative strategies to improve mental health such as e-health technologies should be promoted.

Highlights • The current COVID-19 pandemic is causing severe mental health problems. • We investigated the characteristics of emergency psychiatric consultations during the phase 1 of lockdown in a Department of Mental Health and Addiction located in Lombardy region, Italy, compared to similar period of 2019. • There was a marked reduction in the number of psychiatric emergency consultations. • Some patients were significantly more likely to present to emergency psychiatric consultations during lockdown. • COVID-19 epidemic may have a negative impact on more vulnerable individuals., Background The current COVID-19 pandemic and the consequent containment measures are leading to increasing mental health issues both in psychiatric patients and general population. Objective We aimed to compare the number and characteristics of emergency psychiatric consultations during the phase 1 of lockdown with respect to the same period in 2019 in a Department of Mental Health and Addiction (DMHA) located in Lombardy region. Methods We conducted a cross-sectional study including subjects consecutively admitted to two psychiatric emergency rooms of DMHA in Monza, Lombardy, Italy. Sociodemographic data, clinical characteristics, referred symptoms, diagnosis and information on patients’ illness course following the emergency consultations were collected. No subjects were excluded for the purposes of the study. Results Between February 21st and May 3rd 2020, there was a marked reduction in the number of psychiatric emergency consultations, if compared to the same period of 2019. Subjects who were living in psychiatric residential treatment facilities, had cannabis addiction and a diagnosis of obsessive-compulsive disorder were significantly more likely to present to emergency psychiatric consultations during lockdown. Conclusions COVID-19 epidemic may have a negative impact on more vulnerable individuals. Strategies to enhance relapse prevention and the use of alternative approaches as e-health technologies should be promoted.

Background: Prisoners have a higher prevalence of substance use disorder (SUD) than the nonincarcerated population. Many studies report that an SUD increases the likelihood of psychotic symptoms/disorders. Inmates, therefore, may be at higher risk for psychotic disorders. Objective: The main objectives of this study were to (1) estimate the prevalence of psychotic symptoms in a sample of male inmates with high levels of SUD and (2) verify if type of abuse or other sociodemographic/clinical features are risk factors of psychotic symptoms. In light of the high prevalence of childhood trauma (CT) among inmates, a further objective was to 3) assess whether exposition to CT can predict psychotic symptoms. Method: We included three hundred and nineteen male prisoners, admitted to Monza prison between January 2017 and March 2019. We interviewed participants to collect sociodemographic and clinical information. We administered the Brief Psychiatric Rating Scale (BPRS) and the Drug Abuse Screening Test (DAST) to assess the presence of psychotic symptoms and SUD, respectively. Inmates also completed the Childhood Trauma Questionnaire (CTQ). Results: Data were available for 141 inmates. Forty-five prisoners (31.9%) had psychotic symptoms. Multivariate logistic regression analysis showed that a history of previous incarceration (aOR = 2.98, p = 0.034), opioid abuse (aOR = 5.02, p = 0.008), suicide attempts (aOR = 5.55, p < 0.001), and childhood emotional abuse (aOR = 4.11, p = 0.027) significantly increased the likelihood of psychotic symptoms. Conclusions: Psychotic symptoms are widespread among inmates and are associated with specific risk factors. Prison and jail staff should screen for these factors at the start of an inmate's detention to identify subjects at risk of psychotic symptoms.

Background Since mothers who undergo in vitro fertilization (IVF) may experience more anxiety and depressive symptoms than mothers who conceive naturally, a review of the literature was conducted to investigate whether IVF may be considered a risk factor for the development of anxiety or depression during pregnancy and post-partum. Methods A thorough search of articles in Pubmed, PsycINFO and Isi Web of Knowledge was performed in order to produce a comprehensive review regarding the potential association of in vitro fertilization and anxiety/depression. Results The search resulted in a total of 10 articles. Contradictory results were reported in the articles about the possible association between IVF and the occurrence of anxiety and depressive symptoms both during pregnancy and postpartum period. Three studies found that women who resorted to IVF showed less anxiety and depressive symptoms than those who conceived naturally especially with the progression of pregnancy and in the postpartum. Limitations Vulnerability to affective disorders of women affected by infertility may be independent from the outcome of IVF. Other limits are the limited research in this area, the small sample sizes, the heterogeneity of the tools used to assess affective symptoms. Conclusions The available data indicate that IVF is not associated with perinatal affective symptoms. Women who resorted to IVF could have less perinatal depressive symptoms as the result of a positive outcome of the technique and the satisfaction of the desire to become mothers. Further studies are necessary in order to draw definitive conclusions about this topic.

Background The pathogenetic mechanisms of Bipolar Disorder (BD) have not been totally clarified. Oxidative stress seems to be involved in the etiology of BD, and malondialdehyde (MDA) represents a candidate biomarker for monitoring this aspect in different medical conditions including mood disorders. This article has the objective to critically summarize the available data about the association between MDA and BD. Methods A research in Pubmed, PsycINFO and Isi Web of Knowledge was fulfilled to identify studies in which MDA levels were measured in BD patients for the purpose of securing a comprehensive review concerning the issue. Results We detected 20 articles that satisfied the inclusion criteria: most of them observed higher MDA levels (or Thiobarbituric acid-reactive substances-TBARS) in BD patients compared to healthy controls (HC), although there are some contrasting results, depending in particular on the phase of illness or the inclusion criteria or the methodological differences. Limitations We included studies, exclusively in English, that used different laboratory methods to measure MDA. Conclusions The analysed articles suggest that MDA or TBARS are increased in BD patients with respect to HC, thus supporting the hypothesis that MDA may be a promising and potential biomarker to monitor the course of BD, although further studies are needed to confirm this hypothesis.

Background Intensive Short-Term Dynamic Psychotherapy (ISTDP) is an intervention introduced by Davanloo in order to treat anxiety, mood and somatic symptom, and personality disorders. It is a brief intervention aiming to identify and process painful or forbidden emotions and consequently to override symptoms and self-destructive tendencies. In this review we examine the efficacy of ISTDP on symptoms in patients with Major Depressive Disorder (MDD) and Bipolar Disorder (BD). Methods A thorough search of articles in Pubmed, PsycINFO, Isi Web of Knowledge was carried out in order to obtain available studies of ISTDP for BD and MDD. We included all studies conducted on patients with a diagnosis of MDD or BD and who received ISTDP. Results Eight studies were included. These were two randomized controlled trials and six observational studies. Overall the results of the included manuscripts suggest a positive effect of ISTDP on depressive symptoms for patients affected by mood disorders. Furthermore, they suggest ISTDP may be cost-effective through reducing doctor visits and hospitalizations in follow-up. Limitations Most studies had small samples and consisted of non-randomized trials. Conclusions These are preliminary positive results on the effectiveness of this approach for the treatment of depressive symptoms. They have to be confirmed by studies with larger sample sizes and by comparing this technique with other psychological treatments such as cognitive-behavioral therapy.

Background: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. Aims: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. Methods: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Results: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. Conclusion: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

Background: Attention-deficit/hyperactivity disorder (ADHD) is a disabling disorder. High rates of ADHD have been consistently reported among prisoners. The main objectives were (1) to estimate the prevalence of ADHD symptoms in a sample of male inmates and (2) to investigate the relationship between ADHD symptoms and socio-demographic/clinical features. According to the high prevalence of childhood trauma among inmates, we assessed whether exposition to childhood trauma can be related to the presence of ADHD symptoms. Methods: A total of 159 male prisoners admitted to Monza prison between January 2020 and June 2021 were included. Both Wender Utah ADHD rating scale and adult ADHD self-report scale were administered to assess ADHD symptoms. Moreover, inmates completed the childhood trauma questionnaire. Results: Data were available for 108 inmates. Thirty-five prisoners (32.4%) were found on screening to meet the criteria for symptoms of ADHD. Cocaine use disorder, prescription of mood stabilizers and a history of emotional abuse significantly increased the likelihood of having clinically significant ADHD symptoms. Furthermore, patients who experienced physical neglect resulted in meeting the criteria for ADHD symptoms. Conclusions: ADHD symptoms are widespread among inmates and are associated with specific risk factors. Screening for ADHD should be done to provide appropriate intervention strategies.

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.

Background Prison mental health care is a significant topic which has been already studied and described in literature, particularly because of important implications both in the prison and in the health care system. It's not uncommon that inmates suffering from mental disorders are referred to high security forensic services (HSFS) but, to date, studies assessing factors associated with relevant referrals to these services are missing. So, the aim of our study is to investigate socio-demographic, criminological, psychopathological and toxicological variables among those who were referred to HSFS as compared to their non-referred counterpart. Methods We conducted a cross-sectional study recruiting 159 subjects receiving prison inpatient care in an Italian jail, between January 2010 and August 2015. No subjects were excluded from the study. The mean age was 39. Results About half of included prisoners suffered from personality disorder while one-third from psychotic disorders. >60% of the subjects had comorbid substance use disorders. The odds of being referred to HSFS were related to previous admission (odds ratio [OR] = 5.34, 95% confidence interval [CI] 1.66–17.16), diagnosis of psychosis (OR = 2.79, 95% CI 1.11–7.04) and cannabis use disorder (OR = 2.68, 95% CI 1.14–6.28). Personality disorder was inversely associated to the referral to forensic facilities (OR = 0.37, 95% CI 0.14–0.97). Conclusions Mental health services should improve preventive measures for vulnerable prisoners in order to reduce criminal recidivism and forensic readmission.

BACKGROUND: There is a lack of studies testing accuracy of fast screening methods for alcohol use disorder in mental health settings. We aimed at estimating clinical utility of a standard single-item test for case finding and screening of DSM-5 alcohol use disorder among individuals suffering from anxiety and mood disorders. METHODS: We recruited adults consecutively referred, in a 12-month period, to an outpatient clinic for anxiety and depressive disorders. We assessed the National Institute on Alcohol Abuse and Alcoholism (NIAAA) single-item test, using the Mini- International Neuropsychiatric Interview (MINI), plus an additional item of Composite International Diagnostic Interview (CIDI) for craving, as reference standard to diagnose a current DSM-5 alcohol use disorder. We estimated sensitivity and specificity of the single-item test, as well as positive and negative Clinical Utility Indexes (CUIs). RESULTS: 242 subjects with anxiety and mood disorders were included. The NIAAA single-item test showed high sensitivity (91.9%) and specificity (91.2%) for DSM-5 alcohol use disorder. The positive CUI was 0.601, whereas the negative one was 0.898, with excellent values also accounting for main individual characteristics (age, gender, diagnosis, psychological distress levels, smoking status). DISCUSSION: Testing for relevant indexes, we found an excellent clinical utility of the NIAAA single-item test for screening true negative cases. Our findings support a routine use of reliable methods for rapid screening in similar mental health settings.Copyright © 2016 Elsevier Ireland Ltd. All rights reserved. Language: en

Peripheral biomarkers for suicide have been studied generating mixed results. We investigated the association between serum lipid levels and suicide attempts in subjects with different mental disorders. We conducted a cross-sectional study, including 593 inpatients with schizophrenia spectrum, bipolar, major depressive, and personality disorders, hypothesizing that subjects with lower total cholesterol levels would have higher rates of recent suicide attempts. Contrary to our hypothesis, individuals with lower total cholesterol levels (160 mg/dL) showed lower rates also of suicide attempts (OR adjusted for age and gender: 0.56; one-tailed p = 0.03). Further logistic regression models failed to estimate any association of continuous levels between total/low-density lipoprotein (LDL) cholesterol/ triglycerides, and suicide attempts, also considering diagnosis and suicide methods. An association between lipid profile and suicide attempts in subjects with mental disorders is not fully supported. Further research is needed to clarify the role of biomarkers in suicidal behaviors.

Introduction: Prevention of relapse is a major challenge in schizophrenia, a disease characterized by poor adherence to antipsychotic medication leading to multiple rehospitalizations and a substantial burden-of-care. Methods: We narratively review published clinical data from the development of long-acting injectable (LAI) formulations of antipsychotic drugs and examine the comparative effectiveness of oral versus LAIs in schizophrenia, with a focus on the second- generation LAI antipsychotic aripiprazole. Evidence is presented from studies with naturalistic/pragmatic as well as explanatory trial designs, supported by the clinical experience of the authors. Results: LAI formulations of antipsychotic drugs offer advantages over oral medications and there is good evidence for their use as a first-choice treatment and in younger patients. Key phase III studies have shown aripiprazole once-monthly 400 mg (AOM 400) to be effective and well tolerated, with high rates of adherence and low rates of impending relapse. In a recent randomized trial with a ‘‘naturalistic’’ study design more representative of routine clinical practice, AOM 400 was well tolerated and had significantly greater effectiveness than paliperidone LAI overall and in younger patients aged ≤35 years. Conclusion: Results across the ‘‘full spectrum’’ of efficacy in traditional clinical trials as well as those encompassing the concept of effectiveness in a more naturalistic setting of real-life clinical practice support the use of AOM 400 as a valid long-term treatment option in schizophrenia overall, as well as earlier in the treatment course, and not solely in situations of poor adherence or when oral antipsychotics have failed.

Background: Subjects with bipolar mania may have increased uric acid levels, based on a purinergic system dysfunction with reduced neurotransmission of adenosine. We investigated whether there were differences in uric acid levels between individuals with bipolar disorder (in manic or depressive phases) and those with major depressive disorder. Methods: We conducted a cross-sectional study recruiting 128 subjects with bipolar disorder and 118 with major depressive disorder, admitted to a psychiatric inpatient unit. Standard demographic and clinical information were retrieved from electronic charts and relevant clinical records. Fasting serum values of uric acid, as well as metabolic (total cholesterol, triglycerides, and glycaemia), oxidative stress (albumin, bilirubin), and kidney function (creatinine), parameters, were collected. Results: Subjects with bipolar mania (5.27 ± 1.63 mg/dL), but not those with bipolar depression (4.89 ± 1.94 mg/dL), had higher levels of serum uric acid (p

Introduzione: Numerosi studi riportano un’alta prevalenza di patologie psichiatriche all’interno delle Case Circondariali (CC), in termini di disturbi psicotici, dell’umore e della personalità [1]. Circa il 50% dei soggetti detenuti affetti da malattia psichiatrica presenta inoltre una condizione di "doppia diagnosi", termine da tempo utilizzato per indicare la compresenza nello stesso paziente di un disturbo mentale grave e di un disturbo da uso di sostanze[2,3].Pochi invece sono gli studi riguardanti la prescrizione di terapie psicofarmacologiche nel contesto carcerario, dove sembra emergere una frequenza 4-6 volte superiore rispetto alla popolazione generale,con un’alta percentuale di trattamenti “off-label”[4]. Scopo del lavoro: Valutazione della prescrizione di terapia psicofarmacologica in un campione di soggetti detenuti Materiali e Metodi: E’uno studio trasversale condotto su 423 soggetti detenuti presso la CC di Bergamo nell’aprile 2016. Il campione è stato suddiviso inizialmente in tre gruppi, sulla base di prescrizione di terapia psicofarmacologica (nessun farmaco, una classe di farmaci, due o più classi di farmaci - polifarmacoterapia). Poiché dalla statistica descrittiva emergeva che il 93.3% dei soggetti che assumeva una classe di farmaci, era in terapia con una o più benzodiazepine, si è optato per suddividere il campione in due gruppi: nessuna terapia prescritta o in polifarmacoterapia. I due gruppi sono stati confrontati sulla base di caratteristiche socio-demografiche,psicopatologiche, tossicologiche, criminologiche. Risultati:Il gruppo che non assumeva nessuna terapia psicofarmacologica (n=124) e il gruppo in polifarmacoterapia (n=106) presentavano una differenza statisticamente significativa per età con media (SD) pari a 35,7 (0,95) e 39,7 (1,08), rispettivamente (p= 0.006). I due gruppi presentavano inoltre una differenza statisticamente significativa per le variabili sesso (p=0,014), presenza di diagnosi psichiatrica (p