Search

Supplemental material, sj-pdf-1-isp-10.1177_00207640211057731 for Compulsory and voluntary admissions in comparison: A 9-year long observational study by Stefano Draghetti, Siegfried Alberti, Gianluca Borgiani, Fabio Panariello, Diana De Ronchi and Anna Rita Atti in International Journal of Social Psychiatry

Schizophrenia is a chronic and disabling mental illness affecting millions of people worldwide. A greater proportion of people with schizophrenia tends to be overweight. Antipsychotic medications have been considered the primary risk factor for obesity in schizophrenia, although the mechanisms by which they increase weight and produce metabolic disturbances are unclear. Several lines of research indicate that leptin could be a good candidate involved in pathways linking antipsychotic treatment and weight gain. Leptin is a circulating hormone released by adipocytes in response to increased fat deposition to regulate body weight, acting through receptors in the hypothalamus. In this work, we reviewed preclinical, clinical, and genetic data in order to infer the potential role played by leptin in antipsychotic-induced weight gain considering two main hypotheses: (1) leptin is an epiphenomenon of weight gain; (2) leptin is a consequence of antipsychotic-induced “leptin-resistance status,” causing weight gain.

Excess body weight is one of the most common physical health problems among patients with schizophrenia that increases the risk for many medical problems, including type 2 diabetes mellitus, coronary heart disease, osteoarthritis, and hypertension, and accounts in part for 20% shorter life expectancy than in general population. Among patients with severe mental illness, obesity can be attributed to an unhealthy lifestyle, personal genetic profile, as well as the effects of psychotropic medications, above all antipsychotic drugs. Novel “atypical” antipsychotic drugs represent a substantial improvement on older “typical” drugs. However, clinical experience has shown that some, but not all, of these drugs can induce substantial weight gain. Animal models of antipsychotic-related weight gain and animal transgenic models of knockout or overexpressed genes of antipsychotic receptors have been largely evaluated by scientific community for changes in obesity-related gene expression or phenotypes. Moreover, pharmacogenomic approaches have allowed to detect more than 300 possible candidate genes for antipsychotics-induced body weight gain. In this paper, we summarize current thinking on: (1) the role of polymorphisms in several candidate genes, (2) the possible roles of various neurotransmitters and neuropeptides in this adverse drug reaction, and (3) the state of development of animal models in this matter. We also outline major areas for future research.

Schizophrenia is a serious disorder that affects 1% of the population in the United States and Europe, and is associated with a significant reduction in life expectancy that approaches 20% compared with that of the general population. Current management of patients with schizophrenia involves the increasing use of atypical antipsychotic agents, such as risperidone, quetiapine, olanzapine, and clozapine. The use of these agents has been associated with increased morbidity from obesity,hyperlipidemia, development of new-onset diabetes, and, in rare instances, development of diabetic ketoacidosis. The precise mechanism for the abnormalities in carbohydrate and lipid metabolism is incompletely understood. We investigated whether haloperidol and clozapine, respectively a typical and an atypical antipsychotics, directly affect insulin action in cultured cell models and in vivo. In our experimental paradigms, both haloperidol and clozapine reduced insulin-stimulated glucose uptake in a time- and concentration dependent manner, although with a different efficacy. Indeed, pre-treatment with clozapine, but not with haloperidol, prevented insulin effect on insulin receptor (IR) and IR substrate-1/2 (IRS-1/2) tyrosine phosphorylation. Moreover, both drugs reduced insulin-dependent phosphorylation of protein kinase C-ζ (PKC- ζ), and induced an insulin- independent increase of phosphorylated Akt. These effects were paralleled by increased expression of Ped/Pea-15, an Akt substrate and inducer of insulin resistance. Similar changes of these signalling proteins were detected in caudate-putamen and in skeletal muscle of mice treated with either haloperidol or clozapine. Thus, antipsychotics may impair insulin action, at least in part, by upregulating Ped/Pea-15 and inhibiting activation of PKC- ζ.

Background: Psychiatric disorders are complex, multifactorial illnesses with a demonstrated biological component in their etiopathogenesis. Epigenetic modifications, through the modulation of DNA methylation, histone modifications and RNA interference, tune tissue-specific gene expression patterns and play a relevant role in the etiology of psychiatric illnesses. Objective: This review aims to discuss the epigenetic mechanisms involved in psychiatric disorders, their modulation by environmental factors and their interactions with genetic variants, in order to provide a comprehensive picture of their mutual crosstalk. Methods: In accordance with the PRISMA guidelines, systematic searches of Medline, EMBASE, PsycINFO, Web of Science, Scopus, and the Cochrane Library were conducted. Results: Exposure to environmental factors, such as poor socio-economic status, obstetric complications, migration, and early life stressors, may lead to stable changes in gene expression and neural circuit function, playing a role in the risk of psychiatric diseases. The most replicated genes involved by studies using different techniques are discussed. Increasing evidence indicates that these sustained abnormalities are maintained by epigenetic modifications in specific brain regions and they interact with genetic variants in determining the risk of psychiatric disorders. Conclusion: An increasing amount of evidence suggests that epigenetics plays a pivotal role in the etiopathogenesis of psychiatric disorders. New therapeutic approaches may work by reversing detrimental epigenetic changes that occurred during the lifespan.

This study aimed to characterize the prevalence of eating disorders(EDs), disturbed eating behaviors (DEBs), and emotional eating attitudes (EEAs) among patients affected by endometriosis in order to understand a potential crosslink between this impacting gynecological disease and a Body Mass Index shift. A total of 30 patients were recruited at an endometriosis outpatient clinic in Bologna and were assessed by using standardized instruments and specific questionnaires for EDs, DEBs, and EEAs. Sociodemographic information and endometriosis clinical features and history information were collected by adopting a specific questionnaire. Retrospective reports of lifetime Body Mass Index (BMI) changes, current BMI, peak pain severity during the last menstrual period, and the average of pain intensity during the last intermenstrual period were used for a correlation with the mean score from eating-behavior scales’ assessment. The preliminary results indicate that, although only 3.33% of endometriosis patients are affected by ED, statistically significant differences at the mean scores of DEBs and EEAs assessment scales were found by strati-fying patients on the basis of BMI levels at risk for infertility and coronary heart disease and on the basis ofmoderate/severe pain levels. The enrichment of the sample size and the recruitment of the control group to complete the study enrollment will allow us to investigate more complex and strong correlation findings and to assess the prevalence of EDs among endometriosis patients. Keywords: endometriosis; BMI; pain; eating disorders;disturbed eating behaviors; emotional eating attitudes

BACKGROUND The subsequent waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have represented a dramatic health emergency characterized by significant consequences on mental health. Diachronic variations in the incidence rates of acute relapse of psychiatric disorders may represent significant "sentinel events" for assessing the mental health response to an unprecedented stressful event. AIM To investigate the variation in psychiatric hospitalization rates and differences in sociodemographic and clinical-psychopathological peculiarities at Bologna "Maggiore" General Hospital Psychiatric Ward (GHPW) between the first two waves SARS-CoV-2 pandemic and the same periods of the previous 3 years. The secondary purpose of the study was to suggest a diachronic response pathway to stress by reporting additional literature data on coping strategies. METHODS This observational and retrospective study collected information on admission to the GHPW at the "Maggiore" Hospital in Bologna in the index periods defined as follows: the first period between February 24, 2020 and April 30, 2020 (first epidemic wave) and the second period between October 8, 2020, and January 7, 2021 (second pandemic wave). Absolute numbers and proportion of admitted patients, their sociodemographic and clinical-psychopathological characteristics were compared with the same parameters recorded in the two same periods of the previous 3 years. No strict inclusion or exclusion criteria were provided in the data collection to collect information on all patients requiring acute psychiatric hospitalization. RESULTS During the first wave, there was a significant reduction in hospitalization rates, although there was a simultaneous increase in compulsory hospitalizations and the acute relapse of schizophrenia spectrum and other psychotic disorders. During the second wave, hospitalization rates reached those recorded during the same period of the previous 3 years, mainly due to the rise of bipolar and related disorders, depressive disorders, anxiety disorders, trauma- and stressor-related disorders and suicidal behaviors. CONCLUSION The coping strategies adopted during the first wave of the SARS-CoV-2 pandemic protected the vulnerable population from the general risk of clinical-psychopathological acute relapse, even if they increased the susceptibility to run into schizophrenia spectrum and other psychotic disorder relapses. In the medium-long term (as in the second pandemic wave), the same strategies do not play protective roles against the stress associated with the pandemic and social restriction measures. Indeed, during the second wave of the SARS-CoV-2 pandemic, an increase in total hospitalization rate, suicidal behaviors and the incidence rate of bipolar and related disorders, depressive disorders, anxiety disorders, trauma- and stressor-related disorders was observed.

Clinical and experimental evidence indicates that atypical antipsychotics impair glucose metabolism. We investigated whether clozapine may directly affect insulin action by analyzing insulin signaling in vitro and in vivo. Clozapine reduced insulin-stimulated glucose uptake in PC12 and in L6 cells, representative models of neuron and skeletal muscle, respectively. Consistently, clozapine reduced insulin effect on insulin receptor (IR) by 40% and on IR substrate-1 (IRS1) tyrosine phosphorylation by 60%. Insulin-stimulated Akt phosphorylation was also reduced by about 40%. Moreover, insulin-dependent phosphorylation of protein kinase C-ζ (PKC-ζ) was completely blunted in clozapine-treated cells. Interestingly, clozapine treatment was accompanied by an insulin-independent increase of Akt phosphorylation, with no change of IR, IRS1, and PKC-ζ basal phosphorylation. The cellular abundance of Ped/Pea-15, an Akt substrate and inducer of insulin resistance, was also increased following clozapine exposure, both in the absence and in the presence of cyclohexymide, a protein synthesis inhibitor. Similar as in cellular models, in the caudate–putamen and in the tibialis muscle of clozapine-treated C57/BL/KsJ mice, Akt phosphorylation and Ped/Pea-15 protein levels were increased and PKC-ζ phosphorylation was decreased. Thus, in these experimental models, clozapine deranged Akt function and up-regulated Ped/Pea-15, thereby inhibiting insulin stimulation of PKC-ζ and of glucose uptake. J. Cell. Physiol. 227: 1485–1492, 2012. © 2011 Wiley Periodicals, Inc.

Homer1a is a glutamate-related gene whose expression is induced by antipsychotics acutely (i.e. 90 min after treatment). Acute Homer1a expression is preserved after prolonged antipsychotic treatments, while the effects of short-term discontinuation after chronic antipsychotic treatment have not yet been assessed. Here, we studied early and long-term effects on gene expression by antipsychotics for Homer1a and other components of glutamatergic synapses. In the first paradigm, we evaluated Homer1a acute expression by single administration of antipsychotics (haloperidol 0.8 mg/kg, ziprasidone 10 and 4 mg/kg, clozapine 15 mg/kg). Haloperidol and ziprasidone induced Homer1a in the striatum. Induction by ziprasidone was dose-dependent. These results suggest that acute Homer1a expression correlates with dopaminergic affinity and motor side effects of antipsychotics. In the second paradigm, we studied antipsychotic-mediated long-term changes in Homer1a and glutamate-related genes. Rats were treated (21 days) with haloperidol 0.8 mg/kg, ziprasidone 4 mg/kg, or vehicle, and then sacrificed at 90 min (early time-point) or 24 h (delayed time-point) after last injection. Gene expression at these two time-points was compared. Homer1a preserved its pattern of expression at the early but not at the delayed time-point. Significant changes were also observed for PSD-95. The results suggest that Homer1a preserves its expression profile after chronic antipsychotics.