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Background: Prenatal attachment refers to the affective investment that parents develop towards their unborn baby during pregnancy. Studies have identified depressive symptoms, affect dysregulation, and poor marital adjustment as potential risk factors for poor prenatal attachment. However, no research has concurrently examined these factors. This study aims to explore the simultaneous impact of depressive symptomatology, alexithymia, and couple functioning on prenatal attachment to develop a more comprehensive understanding of the factors shaping the emotional bond between expectant mothers and their fetuses., Methods: This cross-sectional study involved 344 women (mean age = 34.1, SD = 4.6) in their last trimester of pregnancy recruited from the National Health System. The participants completed the Edinburgh Postnatal Depression Scale, the Twenty-Item Toronto Alexithymia Scale, the Dyadic Adjustment Scale, and the Maternal Antenatal Attachment Scale., Results: Regression analyses indicated that perinatal depression and alexithymia negatively affected the Quality of Prenatal Attachment, while Dyadic Cohesion served as a protective factor., Conclusions: The results emphasize the need for early identification of perinatal depression and alexithymia, along with targeted interventions aimed at supporting Dyadic Cohesion during pregnancy. These efforts are crucial for fostering positive prenatal attachment and enhancing maternal mental health.

Fetal Alcohol Spectrum Disorders (FASD) are pervasive disorders that impact various domains of functioning, including self-esteem, familiar and peer relationships, and academic success. The high rate of comorbidity may contribute to delayed diagnosis and treatment. Early diagnosis and intervention that aim at primary symptoms may prevent secondary disabilities and improve the outcomes. No intervention emerged as maximally effective across all symptoms and domains. Consequently, the complex pathophysiology of FASD emphasizes the need for individualized assessment and treatment by using a multimodal approach to intervention.

Background: The COVID-19 pandemic has exacerbated fears and anxieties, potentially influencing maternal perinatal mental health. This study addresses a gap in the literature on fear of COVID-19 in pregnant women, aiming to identify contributing factors., Method: Participants were 401 primiparous women with an average age of 34 years (SD = 4.56) who were recruited through the National Health System during birth support courses. They completed a series of self-reported instruments via an online survey, providing information on their levels of reflective functioning, dyadic consensus, perinatal maternal affectivity, and fear of COVID-19. Pearson's correlation and mediation analysis via a generalized linear model were implemented to analyze the collected data., Results: The relationship between dyadic consensus and fear of COVID-19 was significant and negative. Furthermore, a significant parallel mediation involving perinatal maternal affectivity and reflective functioning was found to the extent that, when these factors were inserted into the model, the direct association between dyadic consensus and fear of COVID-19 became non-significant (total mediation)., Conclusions: The results highlight the importance of dyadic adjustment in alleviating maternal COVID-19 fear, emphasizing interventions promoting couple functioning, mentalization, and addressing affective difficulties. Such approaches are vital for supporting expecting mothers during challenging times like the COVID-19 pandemic.

Glucagon-like peptide-1 receptor (GLP-1R) is a key regulator of glucose metabolism known to be expressed by pancreatic β cells. We herein investigated the role of GLP-1R on T lymphocytes during immune response. Our data showed that a subset of T lymphocytes expresses GLP-1R, which is upregulated during alloimmune response, similarly to PD-1. When mice received islet or cardiac allotransplantation, an expansion of GLP-1R pos T cells occurred in the spleen and was found to infiltrate the graft. Additional single-cell RNA sequencing (scRNA-seq) analysis conducted on GLP-1R pos and GLP-1R neg CD3 + T cells unveiled the existence of molecular and functional dissimilarities between both subpopulations, as the GLP-1R pos are mainly composed of exhausted CD8 T cells. GLP-1R acts as a T cell-negative costimulatory molecule, and GLP-1R signaling prolongs allograft survival, mitigates alloimmune response, and reduces T lymphocyte graft infiltration. Notably, GLP-1R antagonism triggered anti-tumor immunity when tested in a preclinical mouse model of colorectal cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The comprehensive monitoring of licit and illicit drug consumption plays a crucial role in understanding the complexities of patient conditions and designing effective treatment strategies. In this study, the prevalence of psychoactive prescription drugs, classical illicit drugs, and new psychoactive substances (NPS) were objectively assessed in individuals diagnosed with drug-related psychiatric disorders or episodes., Methods: Blood, urine, and hair samples were collected from psychiatric patients admitted to the Mental Health Department and Drug Addiction Service of the North Rome Local Health Authority with declared or suspected psychoactive drug use. Comprehensive drug screening was conducted for all samples using ultra-high-performance liquid chromatography-high-resolution mass spectrometry., Results: A total of 71 blood and urine and 50 hair samples were analyzed to confirm the suitability of the ultra-high-performance liquid chromatography-high-resolution mass spectrometry method for the study purposes. The main substances found in blood and urine were antipsychotics (71.8% and 66.2%) and benzodiazepines (62.0% and 59.2%), respectively, whereas cocaine (84.0%) and antipsychotics (74.0%) was more evident in hair. Z-drugs were detected in blood (7.0%), urine (5.6%), and hair (24%) samples; amphetamines were mainly detected in hair samples (14.0%). Synthetic cathinones were the most frequently detected NPS in hair specimens (8.0%), whereas synthetic cannabinoids were mainly found in blood samples (11.3%). These analyses showed that patients were polydrug users (77.5% detected in blood and urine, and 94.0% in hair)., Conclusions: Comprehensive screening enabled the assessment of past, recent, and actual consumption of psychoactive substances, including licit and illicit drugs and NPS, by psychiatric patients. A thorough understanding of substance consumption patterns can enhance therapeutic interventions and management of psychiatric disorders associated with psychoactive substance use., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Many mental disorders especially chronic serious ones such as schizophrenia-spectrum disorders, are disabling syndromes and impact on patients' social and cognitive functioning, including work activity. Thus, affected patients may show a particular socio-economic vulnerability and need specific social security as well as rehabilitation interventions, including pensions or job-placements. In Italy, the Working Group named 'Employment and Social Security/Insurance in Mental Health (ESSIMH)' was founded in 2020 in order to collect research evidence on mental illness, employment, social security, and rehabilitation., Methods: A descriptive, observational and multi-center study has been conducted in eleven Departments of Mental Health in Italy (Foggia, Brindisi, Putignano, Rome, Bologna, Siena, Pavia, Mantova, Genova, Brescia, and Torino) and involved 737 patients affected by major mental illness and classified in five diagnostic categories: psychoses, mood disorders, personality disorders, anxiety disorders, and others. The data collection was performed in 2020 among patients aged 18 to 70 years old., Results: The rate of employment in our sample was 35.8% ( n  = 264). Occupational disability in our sample was recognized in 58.0% of patients with a mean percentage of severity 51.7 ± 43.1; patients with psychoses (73%) reported higher disability followed by personality (60%) and mood disorders (47.3%) ones. In a logistic multivariate modeling, factors significantly associated with diagnosis were (a) higher level of occupational disability in psychoses; (b) higher number of job- placement programs among psychoses patients; (c) lower level of employment in psychoses; (d) more psychotherapy in personality disorder patients; and (e) more years of MHC program in psychoses patients; factors associated with sex were: (a) higher number of drive licenses among males; (b) more physical activity among males; and (c) higher number of job-placement programs among males., Conclusion: patients affected by psychoses were more likely to be unemployed, reported higher occupational disability as well as received more incentives and rehabilitation interventions. These findings confirmed that schizophrenia-spectrum disorders are disabling and patients need psychosocial support and interventions in the framework of a recovery-oriented treatment., Competing Interests: Conflict of interestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with deficit schizophrenia (SZD) suffer from primary and enduring negative symptoms. Limited pieces of evidence and neuroimaging studies indicate they differ from patients with non-deficit schizophrenia (SZND) in neurobiological aspects, but the results are far from conclusive. We applied for the first time, graph theory analyses to discriminate local and global indices of brain network topology in SZD and SZND patients compared with healthy controls (HC). High-resolution T1-weighted images were acquired for 21 SZD patients, 21 SZND patients, and 21 HC to measure cortical thickness from 68 brain regions. Graph-based metrics (i.e., centrality, segregation, and integration) were computed and compared among groups, at both global and regional networks. When compared to HC, at the regional level, SZND were characterized by temporoparietal segregation and integration differences, while SZD showed widespread alterations in all network measures. SZD also showed less segregated network topology at the global level in comparison to HC. SZD and SZND differed in terms of centrality and integration measures in nodes belonging to the left temporoparietal cortex and to the limbic system. SZD is characterized by topological features in the network architecture of brain regions involved in negative symptomatology. Such results help to better define the neurobiology of SZD (SZD: Deficit Schizophrenia; SZND: Non-Deficit Schizophrenia; SZ: Schizophrenia; HC: healthy controls; CC: clustering coefficient; L: characteristic path length; E: efficiency; D: degree; CC node : CC of a node; CC glob : the global CC of the network; E loc : efficiency of the information transfer flow either within segregated subgraphs or neighborhoods nodes; E glob : efficiency of the information transfer flow among the global network; FDA: Functional Data Analysis; and D min : estimated minimum densities).

Progranulin is a pleiotropic growth factor with important physiological roles in embryogenesis and maintenance of adult tissue homeostasis. While-progranulin deficiency is associated with a broad range of pathological conditions affecting the brain, such as frontotemporal dementia and neuronal ceroid lipofuscinosis, progranulin upregulation characterizes many tumors, including brain tumors, multiple myeloma, leiomyosarcoma, mesothelioma and epithelial cancers such as ovarian, liver, breast, bladder, adrenal, prostate and kidney carcinomas. The increase of progranulin levels in tumors might have diagnostic and prognostic significance. In cancer, progranulin has a pro-tumorigenic role by promoting cancer cell proliferation, migration, invasiveness, anchorage-independent growth and resistance to chemotherapy. In addition, progranulin regulates the tumor microenvironment, affects the function of cancer-associated fibroblasts, and modulates tumor immune surveillance. However, the molecular mechanisms of progranulin oncogenic function are not fully elucidated. In bladder cancer, progranulin action relies on the activation of its functional signaling receptor EphA2. Notably, more recent data suggest that progranulin can also modulate a functional crosstalk between multiple receptor-tyrosine kinases, demonstrating a more complex and context-dependent role of progranulin in cancer. Here, we will review what is currently known about the function of progranulin in tumors, with a focus on its molecular mechanisms of action and regulation.

Migratory birds travel over impressively long distances. Consequently, they have to adopt flight regimes being both efficient-in order to spare their metabolic resources-and robust to perturbations. This paper investigates the relationship between both aspects, i.e., energetic performance and stability, in flapping flight of migratory birds. Relying on a poly-articulated wing morphing model and a tail-like surface, several families of steady flight regime have been identified and analysed. These families differ by their wing kinematics and tail opening. A systematic parametric search analysis has been carried out, in order to evaluate power consumption and cost of transport. A framework tailored for assessing limit cycles, namely Floquet theory, is used to numerically study flight stability. Our results show that under certain conditions, an inherent passive stability of steady and level flight can be achieved. In particular, we find that progressively opening the tail leads to passively stable flight regimes. Within these passively stable regimes, the tail can produce either upward or downward lift. However, these configurations entail an increase of cost of transport at high velocities penalizing fast forward flight regimes. Our model-based predictions suggest that long range flights require a furled tail configuration, as confirmed by field observations, and consequently need to rely on alternative mechanisms to stabilize the flight., (© 2022. The Author(s).)

Although etiological and maintenance cognitive factors have proved effective in predicting the disease course in youths with OCD, their contribution to symptom severity and specific OCD dimensions has been scarcely examined. In a cohort of children and adolescents with OCD (N = 41; mean age = 14; age range = 10-18 yrs.), we investigated whether certain dysfunctional beliefs and cognitive traits could predict symptom severity, and whether they were differentially associated with specific symptom dimensions. We found that self-oriented and socially prescribed perfectionism and intolerance to uncertainty were associated with higher obsession severity, which was not uniquely related to any neuropsychological variable. Greater severity of obsessions and compulsions about harm due to aggression/injury/violence/natural disasters was predicted by excessive concerns with the expectations of other people. Severity in this dimension was additionally predicted by decreasing accuracy in performing a problem-solving, non-verbal reasoning task, which was also a significant predictor of severity of obsessions about symmetry and compulsions to count or order/arrange. Apart from corroborating both the belief-based and neuropsychological models of OCD, our findings substantiate for the first time the specificity of certain dysfunctional beliefs and cognitive traits in two definite symptom dimensions in youth. This bears important clinical implications for developing treatment strategies to deal with unique dysfunctional core beliefs, and possibly for preventing illness chronicity.

Background: Distortions in time processing may be regarded as an endophenotypic marker of neuropsychiatric diseases; however, investigations addressing Bipolar Disorder (BD) are still scarce., Methods: The present study compared timing abilities in 30 BD patients and 30 healthy controls (HC), and explored the relationship between time processing and affective-cognitive symptoms in BD, with the aim to determine whether timing difficulties are primary in bipolar patients or due to comorbid cognitive impairment. Four tasks measuring external timing were administered: a temporal and spatial orienting of attention task and a temporal and colour discrimination task, for assessing the ability to evaluate temporal properties of external events; two other tasks assessed the speed of the internal clock (i.e. temporal bisection and temporal production tasks). Attentional, executive and working memory (WM) demands were equated for controlling additional cognitive processes., Results: BD patients did not show differences in external timing accuracy compared to HC; conversely, we found increased variability of the internal clock in BD and this performance was related to Major Depressive Episodes recurrence and WM functioning. Hence, variability of the internal clock is influenced by the progressive course of BD and impacted by variations in WM., Limitations: Future studies including BD patients stratified by mood episode will further specify timing alterations conditional to the current affective state., Conclusions: Our results shed new light on the clinical phenotypes of BD, suggesting that timing might be used as a model system of the ongoing pathophysiological process., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The attention deficit hyperactivity disorder (ADHD) in women has recently received considerable attention, as research has shown an underestimation of the disorder in females, due to a difference in presentation compared to males: females have a higher risk of having ADHD, without those "disruptive" symptoms that determine the request for help. The purpose of the present narrative review is to identify the neglected clinical problems in the diagnostic and therapeutic intervention of women with ADHD and to analyze the associated comorbid problems. The conducted PubMed search and the relevant literature review on the topic show that the impairment of ADHD in women is underestimated due to the different ways the phenomenon manifests compared to traditional male's symptoms. This underestimation consequently leads to an inadequate treatment and has negative repercussions on the social context in which women are involved in.

Schizophrenia has a heritability of 60-80% 1 , much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Three-dimensional cancer models, such as spheroids, are increasingly being used to study cancer metabolism because they can better recapitulate the molecular and physiological aspects of the tumor architecture than conventional monolayer cultures. Although Agilent Seahorse XFe96 (Agilent Technologies, Santa Clara, CA, United States) is a valuable technology for studying metabolic alterations occurring in cancer cells, its application to three-dimensional cultures is still poorly optimized. We present a reliable and reproducible workflow for the Seahorse metabolic analysis of three-dimensional cultures. An optimized protocol enables the formation of spheroids highly regular in shape and homogenous in size, reducing variability in metabolic parameters among the experimental replicates, both under basal and drug treatment conditions. High-resolution imaging allows the calculation of the number of viable cells in each spheroid, the normalization of metabolic parameters on a per-cell basis, and grouping of the spheroids as a function of their size. Multivariate statistical tests on metabolic parameters determined by the Mito Stress test on two breast cancer cell lines show that metabolic differences among the studied spheroids are mostly related to the cell line rather than to the size of the spheroid. The optimized workflow allows high-resolution metabolic characterization of three-dimensional cultures, their comparison with monolayer cultures, and may aid in the design and interpretation of (multi)drug protocols.

Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To investigate the association between prodromal symptoms of schizophrenia, autonomic activity, and personality functioning., Method: 10 adolescents underwent semi-structured interviews assessing prodromal symptoms of schizophrenia and personality functioning. Cardiac activity was recorded at baseline, during the clinical interviews, and at recovery to assess concurrent changes in autonomic functioning., Results: During the assessment of prodromal symptoms of schizophrenia, participants increased sympathetic activation compared to the recovery condition, and reduced vagal activation compared to the assessment of interpersonal functioning., Conclusions: The findings highlight the importance of integrating the autonomic assessment in clinical psychiatric and psychological practice., Competing Interests: Competing interests: None., (© 2021 Giovanni Fioriti Editore s.r.l.)

Background: Studies showed that affective temperaments and attachment are associated with depressive symptoms, and that they bi-directionally influence each-other. The aim of this study is to explore mechanisms underlying the relationship between the affective temperaments (i.e., depressive, cyclothymic, irritable, hyperthymic and anxious), interview-based attachment, and depressive symptoms., Methods: A sample of 61 adolescents and young adults outpatients were asked to complete the Temperament Evaluation of Memphis, Pisa, and San Diego Autoquestionnaire (TEMPS-A) and the Hamilton Rating Scale for Depression (HAM-D). Attachment was assessed through the Adult Attachment Interview (AAI) and employing a dimensional approach to obtain continuous measures. Mediation models were performed with the affective temperaments as predictor, depressive symptoms as the criterion variable, and attachment dimensions as mediators., Results: Findings showed significant direct effects between all the affective temperaments and depressive symptoms. Only the cyclothymic (β = 0.22; SE = 0.1; 95% IC = 0.05, 0.42) and irritable (β = 0.21; SE = 0.09; 95% IC = 0.04, 0.4) temperaments showed an indirect effect on depressive symptoms through secure-insecure attachment. Dismissing attachment did not predict either the affective temperaments nor depressive symptoms. Preoccupied attachment significantly predicts depressive symptoms and, when controlling for it, the hyperthymic temperament no longer directly associates with depressive symptoms., Limitations: The cross-sectional study design limit conclusion about causation and directionality., Conclusions: Secure attachment could be a protective factor for depressive symptoms for individuals with a cyclothymic or irritable temperament. Differently, the hyperthymic temperament loses its protective role toward depressive symptoms when accounting for preoccupied attachment., (Copyright © 2021. Published by Elsevier B.V.)

Aims: The present investigation aimed at evaluating differences in psychiatric hospitalizations in Italy during and after the lockdown due to the novel coronavirus disease 2019 (COVID-19), compared to the same periods in 2018 and 2019., Methods: We obtained and analyzed anonymized data on psychiatric admissions (n = 4550) from 12 general hospital psychiatric wards (GHPWs) in different Italian regions (catchment area = 3.71 millions of inhabitants). Using a mixed-effects Poisson regression model, we compared admission characteristics across three periods: (a) March 1-June 30, 2018 and 2019; (b) March 1-April 30, 2020 (i.e., lockdown); and (c) May 1-June 30, 2020 (i.e., post-lockdown)., Results: During the COVID-19 lockdown, there was a 41% reduction (IRR = 0.59; p < 0.001, CI: 0.45-0.79) in psychiatric admissions in the enrolled GHPWs with respect to the 2018 and 2019 control period. Conversely, admission rates in the post-lockdown period were similar to those observed in the control period. Notably, a consistent and significant reduction in psychiatric hospitalizations of older patients (aged >65 years) was observed in the lockdown (40%; IRR = 0.60; 95% CI: 0.44-0.82) and post-lockdown (28%; IRR = 0.72; 95% CI: 0.54-0.96) periods. Long-stay admissions (>14 days) increased (63%; IRR = 1.63; 95% CI: 1.32-2.02) during the lockdown and decreased by 39% thereafter (IRR = 0.61; 95% CI: 0.49-0.75). A significant 35% increase in patients reporting suicidal ideation was observed in the post-lockdown period, compared to the rate observed in the 2018 and 2019 control period (IRR = 1.35; 95% CI: 1.01-1.79)., Conclusion: The COVID-19 lockdown was associated with changes in the number of psychiatric admissions, particularly for older patients and long-stay hospitalizations. Increased admission of patients reporting suicidal ideation in the post-lockdown period merits special attention. Further studies are required to gain insight into the observed phenomena., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The aim was to analyse the psychiatric consultations in nine Italian hospital emergency departments, by comparing the lockdown and post-lockdown periods of 2020 with the equivalent periods of 2019. Methods: Characteristics of psychiatric consultations, patients, and drug prescriptions were analyzed. Joinpoint models were used to identify changes in the weekly trend of consultations. Results: A 37.5% decrease in the number of consultations was seen during the lockdown period and 17.9% after the lockdown. The number of individual patients seen decreased by 34.9% during the lockdown and 11.2% after the lockdown. A significant change in the number of consultations from week 11 to week 18 occurred, followed by a gradual increase. There was a higher percentage of patients with previous psychiatric hospitalizations during the lockdown period (61.1 vs. 56.3%) and a lower percentage after the lockdown (59.7 vs. 64.7%). During the lockdown there was a large increase in psychiatric consultations for substance use disorders, whereas more consultations for manic episodes occurred after the lockdown. A 3.4% decrease was observed in consultations for suicidal ideation and planning during the lockdown, followed by an upward rebound after the lockdown, along with an increase in consultations for suicide attempts. During lockdown antipsychotic and benzodiazepine prescriptions increased by 5.2 and 4.1%, respectively. After the lockdown, the number of compulsory hospitalizations was higher than in 2019. Conclusions: We observed a decrease of psychiatric consultations during and after the lockdown. There was an increase in consultations for manic episodes and suicidality after the lockdown. The focus of psychiatric services must remain high particularly in this latter period., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Balestrieri, Rucci, Amendola, Bonizzoni, Cerveri, Colli, Dragogna, Ducci, Elmo, Ghio, Grasso, Locatelli, Mencacci, Monaco, Nicotra, Piccinini, Pischiutta, Toscano, Vaggi, Villari, Vitalucci, Castelpietra and Bondi.)

The early and correct assessment of psychomotor agitation (PMA) is essential to ensure prompt intervention by healthcare professionals to improve the patient's condition, protect healthcare staff, and facilitate future management. Proper training for recognizing and managing agitation in all care settings is desirable to improve patient outcomes. The best approach is one that is ethical, non-invasive, and respectful of the patient's dignity. When deemed necessary, pharmacological interventions must be administered rapidly and avoid producing an excessive state of sedation, except in cases of severe and imminent danger to the patient or others. The purpose of this brief review is to raise awareness about best practices for the management of PMA in emergency care situations and consider the role of new pharmacological interventions in patients with agitation associated with bipolar disorder or schizophrenia.

Background: Among Family-Based Services for the treatment of severe mental illnesses, multi-family models gained particular attention, given the potential usefulness of mutual feed-back, motivation and encouragement among families. Methods: The Psychodynamic Multi-Family Group Model has been proposed since 1997 in some Community Mental Health Services in Rome. Since 2011 multifamily groups are held weekly in all the six Districts of the Department of Mental Health that serves a population of more than one million people, and data have been collected since 2015 in three Districts. A total of 794 individuals attended the meetings in the period 2015-2019. Results: Eighty-six percent of those who started, attended more than one meeting. The mean of occurrences of participation among patients was 18.6, among mothers 25.6 and among fathers 21.6. The 794 participants belonged to 439 family units, among which 180 comprised only the patient, 76 only parent(s) or other close person(s), and 183 comprised parent(s) or close person(s) with the patient. Patients participating alone were older than those of families who participated as a whole. Families including the patient showed the longest duration of attendance and the highest prevalence of a diagnosis of schizophrenia in the index patient. Families who had been attending the multifamily groups since a long time maintained a high rate of attendance. Conclusions: Multifamily groups represent a setting where patients can meet with other people and professionals in a free still structured way, and with not strictly therapeutic objectives. The high number of patients who attended alone suggests that such participation corresponds to a self-perceived need of open and free setting facilitating sharing of problems and solutions. The good tenure of the interventions, the high participation, and the feasibility in the long-term suggest that multifamily groups can be implemented in the mental health services of a large city, are sustainable over many years, and can represent a valuable resource for many patients and families., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Maone, D'Avanzo, Russo, Esposito, Goldos, Antonucci, Ducci and Narracci.)

Although personality is a widely discussed topic within the academic field, little is still known about its role in affecting psychopathology, specifically schizophrenia, which can involve psychosis. While the existing literature connects these fields, it is necessary to deepen the knowledge about the relationship between these and the role that personality disorders and traits have on such psychopathology. With the implementation of the AMPD in the DSM-5 and the related assessment of impairment in personality functioning and pathological personality traits, moving from traditional models as the FFM Model of Personality, the present systematic review aims to clarify and summarize the state of the art of the studies regarding this topic. According to the Prisma Statement, literature collection was built based on two databases: PubMed and PsycINFO, and the search focused on recent studies in a period from 2011 to 2020 to check for studies consistent with recent updates. The search process started from 866 articles and ended with 10 selected studies from the two databases, covering years from 2011 to 2020. Studies differ in sample size, measures, aim, and outcome making the present literature review diversified in its content. This review gathers evidence and sheds light on the complexity of these topics and their interconnection. Future studies may be required to clarify the clinical implications of these aspects, aiming at incrementing treatments with a more specific focus on assessment that can provide enhanced preventions., Competing Interests: Competing interests: None., (© 2021 Giovanni Fioriti Editore s.r.l.)

Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration. In contrast, RT112 cells are more prone to form spheroids. RT112 cells produce more ATP by glycolysis and OXPHOS, present overall higher metabolic plasticity and are less sensitive than 5637 to nutritional perturbation of cell proliferation and migration induced by treatment with 2-deoxyglucose and metformin. On the contrary, spheroid formation is less sensitive to metabolic perturbations in 5637 than RT112 cells. The ability of metformin to reduce, although with different efficiency, cell proliferation, sphere formation and migration in both cell lines, suggests that OXPHOS targeting could be an effective strategy to reduce the invasiveness of Grade 2 bladder cancer cells.

Background: Many researchers who evaluated psychological distress during the transition to parenthood agree in identifying pregnancy as the most sensitive period for the onset of psychiatric symptomatology for both parents. Furthermore, research highlights a correlation between symptoms experienced by fathers in relation to those experienced by mothers., Objective: The aim of this study was to investigate whether dyadic functioning influences the level of psychiatric symptomatology in couples expecting their first child. Participants were 137 couples expecting their first child; they were recruited at the San Filippo Neri and the Santo Spirito hospitals in Rome (ASLROMA1). We used an Actor-Partner Interdependence Model (APIM) to test the interdependence of both partners and the effect of dyadic relationships on psychiatric symptoms in the couple., Results: The overall test of distinguishability yielded a chi square value of 122.167 (23 df; p < .001). The actor-partner interdependence model showed significant paths between couple coping and psychiatric symptomatology. Specifically, we found that the quality of couple coping perceived by the mother negatively predicted maternal psychiatric symptomatology, and the quality of couple coping perceived by the father negatively predicted paternal psychiatric symptomatology. Furthermore, the quality of couple coping perceived by the father negatively predicted maternal psychiatric symptomatology., Conclusions: The results of this study confirm that dyadic adjustment is an important element for the development of effective interpersonal relationships. These data highlight the importance of promoting psycho-educational and clinical courses and programs for the development of social support with future parents., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interests to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The following authors have double affiliations: Stefania Boccia, Marco Di Nicola and they should read.

Background: Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis., Methods: 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects., Results: five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster., Discussion: CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this system, and especially of the SLC6A4 gene, may be associated with psychiatric disorders. In this study we aimed to evaluate the pleiotropic nature of SLC6A4 alterations and their association with the overall risk of brain diseases rather than disorder-specific. SLC6A4 variants, namely 5HTTLPR, STin2, rs2066713, rs25531, rs4251417, rs6354 and rs7224199 were investigated in 4 independent cohorts of subjects with specific psychiatric disorders, including Alcohol dependence disorder (ALC), Alzheimer disease (ALZ), Schizophrenia (SCZ) and Bipolar disorder (BPD). Other variables (biochemical parameters and Psychiatric scales scores) were also tested for association. SLC6A4 polymorphisms are not associated with the risk of developing major psychiatric disorders (SCZ and BPD); however some signals were detected in ALC (HTTLPR p d  = 9.25 × 10 -03 , p r  = 7.24 × 10 -03 ; rs2066713 p d  = 6.35 × 10 -08 ; rs25531 p d  = 2.95 × 10 -02 ; rs4251417 p d  = 2.46 × 10 -03 ), and ALZ (rs6354 p r  = 1.22 × 10 -02 ; rs7224199 p d  = 1.00 × 10 -08 , p r  = 2.65 × 10 -02 ) cohorts. Some associations were also observed on exploratory analyses. Our findings did not reveal any major influence on SCZ and BPD development; On the other hand, some alteration of the SLC6A4 sequence were associated with an increased risk of ALC and ALZ disorders, suggesting common pathways. The results of this study should be carefully interpreted since it suffers of some inherent limitations (e.g. cohort size, slight ethnic heterogeneity). Further analyses may provide better detail on the molecular processes behind SLC6A4 alterations.

Objective: Recent research suggests that early signs of schizophrenia can be detected several years before its onset. Evidence suggests that the identification of at-risk individuals before the psychotic onset can significantly improve the course of the disorder. However, instruments employed for the detection of prodromal symptoms are far from being accurate in the prediction of a future transition to psychosis. The aim of the present review is to summarize literature on the early signs of schizophrenia and to identify physiological markers that may aid the identification of the disorder before psychotic transition., Method: This critical review includes studies published between 1979 and 2018 that were indexed in major databases with the following keywords: schizophrenia, prodromal phase, basic symptoms, autonomic nervous system, heart rate variability., Results: The examination of the relevant literature showed that, despite recent progress in the identification of at-risk states, the currently employed instruments do not allow an effective prediction of a future psychotic onset. Also, evidence suggests a significant association between alterations in the autonomic nervous system (ANS) functioning and psychotic disorders. However, literature on the association between ANS functioning and at-risk states for psychosis is still scarce. The addition of physiological risk indicators may represent a step forward in the detection of at-risk individuals., Conclusions: Overall, the present literature review highlights that a future schizophrenic onset cannot be strongly predicted with current available measures. Given the established correlation between schizophrenia and autonomic dysregulation, an investigation of the ANS functioning in individuals who are at increased risk of developing schizophrenia may be particularly useful to improve the quality of the assessment, to identify at an early stage the dysregulated physiological patterns that have been linked with schizophrenia, and therefore to develop tailored interventions. Accordingly, it is crucial that future research investigates the presence of autonomic deficits in individuals at risk for psychosis., Competing Interests: Declaration of interest: none, (© 2019 Giovanni Fioriti Editore s.r.l.)

Shared genetic vulnerability between schizophrenia (SCZ) and bipolar disorder (BP) was demonstrated, but the genetic underpinnings of specific symptom domains are unclear. This study investigated which genes and gene sets may modulate specific psychopathological domains and if genome-wide significant loci previously associated with SCZ or BP may play a role. Genome-wide data were available in patients with SCZ (n = 226) or BP (n = 228). Phenotypes under investigation were depressive and positive symptoms severity, suicidal ideation, onset age and substance use disorder comorbidity. Genome-wide analyses were performed at gene and gene set level, while 148 genome-wide significant loci previously associated with SCZ and/or BP were investigated. Each sample was analyzed separately then a meta-analysis was performed. SH3GL2 and CLVS1 genes were associated with suicidal ideation in SCZ (p = 5.62e-08 and 0.01, respectively), the former also in the meta-analysis (p = .01). SHC4 gene was associated with depressive symptoms severity in BP (p = .003). A gene set involved in cellular differentiation (GO:0048661) was associated with substance disorder comorbidity in the meta-analysis (p = .03). Individual loci previously associated with SCZ or BP did not modulate the phenotypes of interest. This study provided confirmatory and new findings. SH3GL2 (endophilin A1) showed a role in suicidal ideation that may be due to its relevance to the glutamate system. SHC4 regulates BDNF-induced MAPK activation and was previously associated with depression. CLVS1 is involved in lysosome maturation and was for the first time associated with a psychiatric trait. GO:0048661 may mediate the risk of substance disorder through an effect on neurodevelopment/neuroplasticity., (Copyright © 2018. Published by Elsevier Inc.)

Schizophrenia is a severe, chronic mental disorder. Schizophrenia is visualized as an accelerated cellular aging syndrome characterized by early onset of cardiovascular disease causing premature mortality. In human aging involves alterations in telomere length (TL). To investigate the presence of TL shortening in schizophrenia and psychiatric syndromes associated, this condition was studied in leukocytes (LTL) of a sample of patients suffering from schizophrenia and other psychotic disorders, and compared with a group of non-psychiatric controls. We explored the relationship between LTL and age, gender, and smoking habit with the aim to control whether these potential confounding factors may influence the rate of telomeres shortening. We also performed a new comprehensive meta-analysis including studies on LTL in schizophrenia patients compared to healthy subjects published in the last two years and the results of the present study. Our results suggest that a diagnosis of schizophrenia, more than gender, age, cigarette smoking or alcohol drinking, is the most important condition responsible of the LTL shortening. A strong LTL shortening was observed in patients affected by schizophrenia, Schizoaffective disorder, and Psychosis not otherwise specified when they were younger than 50 years, while in the group of older subjects no major differences were observed. Additional evidence supporting the causal link of schizophrenia with accelerated telomeres shortening came from the analysis of the updated meta-analysis. The availability of a personalized profile of mechanistic pathways, risk factors, and clinical features may pose the basis for a rehabilitative treatment addressing individual needs of the psychiatric patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Patients with severe psychotic disorders such as schizophrenia, schizoaffective, and bipolar disorders frequently suffer from concomitant substance use disorders (SUDs)-Dual Disorder (DD) patients. In order to better understand current practices for management of patients with psychotic episodes and concomitant SUD in Italy, we carried out a survey of psychiatrists on current routine practice among prescribers. These aspects can help to identify at-risk patients, improve current prescribing practices, and favor early intervention. An ad hoc survey of 17 questions was administered to psychiatrists via electronic polling and on-line distribution; 448 completed questionnaires were collected. Comorbid substance abuse was most frequently diagnosed within the context of anxiety disorder (46%), followed by bipolar disorder (25%), and schizophrenia/schizoaffective disorder (12%). The vast majority of respondents felt that patient management was becoming more complex due to substance abuse. The areas reported to be most affected in patients with SUD were functioning, interpersonal relations, and impulsivity, while sensory perception disorders, ideation, agitation, and impulsivity were the most frequently reported symptoms. In the acute setting, haloperidol was used as the first-line agent of choice followed by aripiprazole and olanzapine. In the maintenance phase, aripiprazole was the dominantly used first-line agent, followed by olanzapine. Almost half of respondents used long-acting agents, while about one-third did not. Among those prescribing long-acting agents, efficacy, control of impulsivity, and control of specific symptoms were cited as motivators, while in the maintenance phase, better adherence, and tolerability were mainly cited. From the responses to the present survey, it is clear that the respondents are aware of the problem of SUD in psychotic patients. While treatment be optimized in terms of the choice and formulation of antipsychotics, greater emphasis should be placed on efficacy, tolerability, and the negative metabolic consequences of some antipsychotics. When considering the ideal antipsychotic, long-acting agents were considered to be superior in reducing relapse, even if current treatment guidelines often give preference to oral formulations.

Background: Novel Psychoactive Substances (NPS) are a heterogeneous class of synthetic molecules including synthetic cannabinoid receptor agonists (SCRAs). Psychosis is associated with SCRAs use. There is limited knowledge regarding the structured assessment and psychometric evaluation of clinical presentations, analytical toxicology and clinical management plans of patients presenting with psychosis and SCRAs misuse., Methods: We gathered information regarding the clinical presentations, toxicology and care plans of patients with psychosis and SCRAs misuse admitted to inpatients services. Clinical presentations were assessed using the PANSS scale. Vital signs data were collected using the National Early Warning Signs tool. Analytic chemistry data were collected using urine drug screening tests for traditional psychoactive substances and NPS., Results: We described the clinical presentation and management plan of four patients with psychosis and misuse of SCRAs., Conclusion: The formulation of an informed clinical management plan requires a structured assessment, identification of the index NPS, pharmacological interventions, increases in nursing observations, changes to leave status and monitoring of the vital signs. The objective from using these interventions is to maintain stable physical health whilst rapidly improving the altered mental state.

Background: Long-acting injectable (LAI) antipsychotics can improve medication adherence and reduce hospitalisation rates compared with oral treatments. Paliperidone palmitate (PAL) and aripiprazole monohydrate (ARI) LAI treatments were associated with improvements in global functioning in patients with schizophrenia., Objective: The objective of this study was to assess the predictive factors of better overall functioning in patients with chronic schizophrenia and schizoaffective disorder treated with PAL and ARI., Method: Enrolled were 143 (97 males, 46 females, mean age 38.24 years, SD = 12.65) patients with a diagnosis of schizophrenia or schizoaffective disorder, whom we allocated in two groups (PAL and ARI treatments). We assessed global functioning, amount of oral medications, adherence to oral treatment, and number of hospitalisations before LAI introduction and at assessment time point., Results: Longer treatment time with LAIs (p < .001), lower number of oral drugs (p < .001), and hospitalisations (p = .002) before LAI introduction, and shorter duration of illness (p = .038) predicted better Global Assessment of Functioning scores in the whole sample (R 2  = 0.337)., Conclusion: Early administration and longer duration of ARI or PAL treatments could play a significant role in improving global functioning of patients with schizophrenia and schizoaffective disorder. Better improvement in functioning could be achieved with ARI in young individuals with recent illness onset and PAL in patients at risk for recurrent hospitalisations., (Copyright © 2018 John Wiley & Sons, Ltd.)

The brain structural correlates of cognitive and psychopathological symptoms within the active phase in severely psychotic schizophrenic inpatients have been rarely investigated. Twenty-eight inpatients with a DSM-5 diagnosis of Schizophrenia (SZ), admitted for acute psychotic decompensation, were assessed through a comprehensive neuropsychological and psychopathological battery. All patients underwent a high-resolution T1-weighted magnetic resonance imaging investigation. Increased psychotic severity was related to reduced grey matter volumes in the medial portion of the right superior frontal cortex, the superior orbitofrontal cortex bilaterally and to white matter volume reduction in the medial portion of the left superior frontal area. Immediate verbal memory performance was related to left insula and inferior parietal cortex volume, while long-term visuo-spatial memory was related to grey matter volume of the right middle temporal cortex, and the right (lobule VII, CRUS1) and left (lobule VI) cerebellum. Moreover, psychotic severity correlated with cognitive inflexibility and negative symptom severity was related to visuo-spatial processing and reasoning disturbances. These findings indicate that a disruption of the cortical-subcortical-cerebellar circuit, and distorted memory function contribute to the development and maintenance of psychotic exacerbation.

Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments. Genomic DNA was isolated from peripheral white blood cell samples and polymorphisms were genotyped by pyrosequencing technology. Although no differences were observed between allele and genotype frequencies for all polymorphisms and suicide attempt (SA), a polygenic risk score was detected for three genes HTR2A (A-1438G), TPH1 and TPH2 increasing the prediction of SA risk (Thresh=0.43, p=0.038, R 2 =0.053). Moreover some nominal associations were obtained after gender and phenotypic dissection stratification (TEMPS-A, TEMPs-H, GSMD, SHSS, GAF, CGI) for SLC6A4 (5-HTTLPR), HTR1A (C-1019G), HTR2A (A-1438G), TPH1 (A799C) and GNB3 (C825T) genes, that were lost after Bonferroni correction. This is a first evidence that specific additive combinations of genes could increase the prediction of SA risk and that gender and phenotypic dissection could influence the association of the genes with SA. This could represent a further study also for future meta-analyses on larger samples., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The study aims to identify independent predictors of physical restraint in acute psychiatric patients and to determine the predictive power of a risk assessment model centered on psychopathological dimensions. We included 1552 patients admitted to a psychiatric intensive care unit over a 5-year period. Patients were rated on the Brief Psychiatric Rating Scale (BPRS-E) at admission. Principal axis factoring (PAF) with varimax rotation was performed on BPRS-E items to identify psychopathological factors. Multiple logistic regression analysis was performed. PAF pointed six factors: positive symptoms, negative symptoms, resistance, activation, negative affect, and disorganization. Male sex, younger age, proposal for compulsory admission, severity of symptoms, resistance, activation, and disorganization were identified as independent predictors. Negative symptoms and negative affect were instead protective factors. The BPRS-E factors, when added to other sociodemographic and clinical variables, significantly increased the predictive power of the model. Our findings suggest that a systematic evaluation of the psychopathological dimensions can be usefully included in the early risk assessment of restraint.

Social values and concepts have played a central role in the history of mental health care. They have driven major reforms and guided the development of various treatment models. Although social values and concepts have been important for mental health care in the past, this Personal View addresses what their role might be in the future. We (DG, PH, and SP) did a survey of professional stakeholders and then used a scenario planning technique in an international expert workshop to address this question. The workshop developed four distinct but not mutually exclusive scenarios in which the social aspect is central: mental health care will be patient controlled; it will target people's social context to improve their mental health; it will become virtual; and access to care will be regulated on the basis of social disadvantage. These scenarios are not intended as fixed depictions of what will happen. They could, however, be useful in guiding further debate, research, and innovation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The study aimed at investigating the role of the hippocampal subfields in cognitive insight and the clinical and neuropsychological underpinnings of the related two sub-dimensions, Self-Reflectiveness (SR), i.e., openness to external feedback, and Self-Certainty (SC), i.e., unrealistic overconfidence in one's opinions. In order to do this, 45 patients with a diagnosis of schizophrenia and 45 age- and gender-matched healthy control subjects (HC) were administered the Beck Cognitive Insight Scale (BCIS), along with neuropsychological, clinical and psychopathological assessment, and underwent an MRI investigation. Hippocampal segmentation was carried out. Regression analyses were performed for BCIS indexes, volumetric parameters of hippocampal subfields and clinical and neuropsychological variables. Results highlighted that in the schizophrenia group, higher levels of SC were related to reduced volume of the left presubiculum, and worse episodic memory. No significant relationship emerged for the SR index. There was no significant relationship between any of the BCIS indexes and volumetric data of the hippocampal subfields in the HC group. Our data support the hypothesis that unrealistic self-overconfidence in schizophrenia is related to the hippocampal presubiculum atrophy, which is involved in episodic memory and cognitive control and is supposed to be underpinned by difficulty in integrating new memories and thus in generating new hypotheses about the self., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Schizophrenia is a severe mental disease that affects approximately 1% of the population with a relevant chronic impact on social and occupational functioning and daily activities. People with schizophrenia are 2-2.5 times more likely to die early than the general population. Non-adherence to antipsychotic medications, both in chronic and first episode schizophrenia, is one of the most important risk factors for relapse and hospitalization, that consequently contributes to increased costs due to psychiatric hospitalization. Atypical long-acting injectable (LAI) antipsychotics can improve treatment adherence and decrease re-hospitalization rates in patients with schizophrenia since its onset. The primary goals in the management of schizophrenia are directed not only at symptom reduction in the short and long term, but also at maintaining physical and mental functioning, improving quality of life, and promoting patient recovery., Aim: To propose a scientific evidence-based integrated model that provides an algorithm for recovery of patients with schizophrenia and to investigate the effectiveness and safety of antipsychotics LAI in the treatment, maintenance, relapse prevention, and recovery of schizophrenia., Methods: After an accurate literature review we identified, collected and analyzed the crucial points in taking care schizophrenia patients, through which we defined the steps described in the model of management and the choice of the better treatment option. Results. In the management model we propose, the choice of a second generation long acting antipsychotic, could allow from the earliest stages of illness better patient management, especially for young individuals with schizophrenia onset, a better recovery and significant reductions of relapse and health care costs. LAI formulations of antipsychotics are valuable, because they help patients to remain adherent to their medication through regular contact with healthcare professionals and to prevent covert non-adherence., Conclusions: The proposed schizophrenia model of management could allow better patient management and recovery, in which the treatment with LAI formulation is a safe and effective therapeutic option. This new therapeutic approach could change the cost structure of schizophrenia by decreasing costs with efficient economic resource allocation guaranteed from efficient diagnostic and therapeutic pathways.

Background: Communicating about delusions can be challenging, particularly when a therapeutic relationship needs to be established in acute care. So far, no systematic research has explored how psychiatrists address patients' delusional beliefs in first meetings in acute care. The aim of this study was to describe how psychiatrists address patients' delusional experiences in acute in-patient care., Methods: First meetings between five psychiatrists and 14 patients in acute care were audio-recorded and analysed using thematic content analysis., Results: 296 psychiatrist statements about delusions were identified and coded. Three commonly used approaches (with a total of 6 subthemes) were identified. The most common approaches were eliciting the content (1 subtheme: eliciting content and evidence) and understanding the impact (3 subthemes: identifying emotions, exploring links with dysfunctional behaviour and discussing reasons for hospital admission) while questioning the validity of the beliefs (2 subthemes: challenging content and exploring alternative explanations) was less common. The last approach sometimes put patients in a defensive position., Conclusions: Psychiatrists commonly use three approaches to address patients' delusions in the first meeting in acute in-patient care. Questioning the patients' beliefs can lead to disagreement which might hinder establishing a positive therapeutic relationship. Future research should explore the impact of such an approach on outcomes and specify to what extent questioning the validity of delusional beliefs is appropriate in the first meeting.

Non-Communicable Diseases (NCDs) are among the most pressing global health problems of the twenty-first century. Their rising incidence and prevalence is linked to severe morbidity and mortality, and they are putting economic and managerial pressure on healthcare systems around the world. Moreover, NCDs are impeding healthy aging by negatively affecting the quality of life of a growing number of the global population. NCDs result from the interaction of various genetic, environmental and habitual factors, and cluster in complex ways, making the complex identification of resulting phenotypes not only difficult, but also a top research priority. The degree of complexity required to interpret large patient datasets generated by advanced high-throughput functional genomics assays has now increased to the point that novel computational biology approaches are essential to extract information that is relevant to the clinical decision-making process. Consequently, system-level models that interpret the interactions between extensive tissues, cellular and molecular measurements and clinical features are also being created to identify new disease phenotypes, so that disease definition and treatment are optimized, and novel therapeutic targets discovered. Likewise, Systems Medicine (SM) platforms applied to extensively-characterized patients provide a basis for more targeted clinical trials, and represent a promising tool to achieve better prevention and patient care, thereby promoting healthy aging globally. The present paper: (1) reviews the novel systems approaches to NCDs; (2) discusses how to move efficiently from Systems Biology to Systems Medicine; and (3) presents the scientific and clinical background of the San Raffaele Systems Medicine Platform.

Background: Insight affects adherence and treatment outcome and relates to cognitive impairment and psychopathology. We investigated the relationship of insight with cognition in patients with major depression, schizophrenia and bipolar disorder in acute psychiatric care, long-term inpatient, and outpatient settings., Methods: Eighty-one patients (women, 59.5%; age, 45.9 ± 13.5 years; 27 in each setting group; 33.3% with DSM-IV bipolar disorder, 39.5% with unipolar major depression, and 27.2% with schizophrenia) underwent the Wisconsin Card Sorting Test (WCST) to test flexibility, clinician-rated Scale to Assess Unawareness of Mental Disorder (SUMD), and self-rated Insight Scale (IS) to assess insight/awareness., Results: Poor performance on the WCST correlated with higher SUMD scores such as current psychiatric illness unawareness, impaired symptom attribution, unawareness of medication effect, or of social consequences, but not with IS scores. The latter correlated with days on continuous treatment. Patients receiving psycho-education showed greater symptom awareness compared to patients treated with drugs alone. Cognitive flexibility and diagnostic category did not correlate. Poor insight corresponded with severe mental illness, particularly acute psychosis., Conclusions: Treatment setting specificity reflects psychopathology and severity. Insight is inversely proportional to illness severity and cognitive flexibility, which is also affected by psychopathology. Limitations comprise group heterogeneity, cross-sectional design, and limited sample size., (Copyright © 2012 S. Karger AG, Basel.)

Cotard’s syndrome is a delusional syndrome, first described in the 1880ies by Cotard, characterized by a nihilistic delusions about the self and/or the world. In same other cases there is an intense nihilistic belief that the patient’s entire body or parts of it are disintegrated or dead. The syndrome is often associated with severe depression, but are also described neurological cases. Koro was described a little later from Asia and consisted in the belief that one’s own genitalia are shrinking or disappearing and death will ensue thereafter, but there are many cultural variants and the syndrome may present in an incomplete form. We report on a KLS sharing more features with annihilation delusions, such as Cotard’s syndrome. In KLS, the délire de négation may be limited to localized systems or organs. We believe that some complete and incomplete forms of Koro, when embedded in a depressive core, may represent a variant of Cotard’s delusion. In fact, our patient did not reach a complete denial of his entire body, but rather focused on sexual identity. We analysed the psychosexual issues of our case according to Kretschmer’s 1918 view of a “bipolar setting” between sthenic and asthenic characters of a patient suffering from sensitive delusions of (self-) reference. This view may allow us to relate the personological character to the genetic comprehensibility of the delusion.

White matter hyperintensities (WMHs) refer to areas of hyperintense signal on T2- or proton density-weighted brain magnetic resonance imaging. Although WMHs are a common finding in patients with bipolar disorder (BD), particularly with a later disease onset, some studies report a higher frequency of WMHs only in unipolar affective disorders. We reviewed the literature examining examining both the severity and presence of WMHs in late life and particularly in individuals with late-onset BD (LOBD). Studies investigating white matter lesions in LOBD were systematically retrieved and the reference lists of these studies were scanned for additional relevant studies of neuroimaging in LOBD. The majority of neuroimaging studies reported an association between older age and LOBD and the presence of WMHs in LOBD. Also, we found in a small sample of patients preliminary evidence of a significant relationship between older age with late-onset BD and WMHs having a higher prevalence of cardiovascular and cerebrovascular risk factors. In conclusion over 60 years older individuals with LOBD and WMHs might have a type of illness characterized by more neuropathological changes and biologically different compared to non LOBD. This is consistent with the hypothesis of vascular mania. WMHs could be a reliable biological risk marker for late onset mood disorders.

Background: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study., Methods/design: The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome., Discussion: The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.

The aims of the present study were to examine clinical, personality, and sociodemographic predictors of suicide risk in a sample of inpatients affected by major affective disorders. The participants were 74 inpatients affected by major depressive disorder or bipolar disorder-I. Patients completed a semi-structured interview, the Beck Hopelessness Scale, the Aggression Questionnaire, the Barratt Impulsiveness Scale, and the Hamilton scales for depression and anxiety. Over 52% of the patients were high suicide risks. Those at risk reported more severe depressive-anxious symptomatology, more impulsivity and more hostility. Impulsivity, the use of antidepressants, anxiety/somatization, and the use of mood stabilizers (a negative predictor) resulted in accurate predicting of suicide intent. Impulsivity and antidepressant use were the strongest predictors even after controlling for several sociodemographic and clinical variables.