A hybrid classical/quantum approach to cluster fragmentation dynamics: Application to the vibrational predissociation of He2Cl2

A new hybrid classical/quantum method is proposed and applied to investigate the vibrational predissociation (VP) dynamics of the He2Cl2 complex. The full dimensionality of the system (assuming zero total angular momentum) is included in the method. The VP process He2Cl2 is dominated by a sequential mechanism of dissociation of the two van der Waals bonds. The hybrid approach describes the first weak bond fragmentation classically, and the second one quantum mechanically. The rotational distribution of the Cl2 fragment is calculated both with the hybrid method and with a fully classical trajectory simulation, and compared with the experimental distribution. The hybrid distribution is found to agree very well with the experimental one, and to involve a substantial improvement with respect to the classical result. © 1998 American Institute of Physics.This work has been supported by the D.G.I.C.Y.T. Grant No. PB95-0071 ~Spain! and the Spanish-French cooperation program PICASSO No. HF1996-0232.Peer Reviewe

Real-World Data on the Adverse Metabolic Effects of Second-Generation Antipsychotics and Their Potential Determinants in Adult Patients: A Systematic Review of Population-Based Studies

This independent research and manuscript writing and editing activities were funded by unconditional grant from Angelini Pharma Espan˜a SLU. Angelini Pharma Espan˜a SLU also funded the journal’s rapid service fee.The authors thank Isabel San Andre´s (Incimed, Madrid, Spain) for performing the literature searchThis article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.Introduction To assess the risk of occurrence and potential determinants of metabolic disorders in adult patients treated with second-generation antipsychotics (SGAs) under real-world practice conditions. Methods MEDLINE, EMBASE, and PsycInfo were searched in July 2019 from database inception. We included population-based, longitudinal, comparative studies that report the results of the outcomes of interest for adult participants, including diabetes, ketoacidosis, hyperosmolar hyperglycemic state, weight gain/obesity, dyslipidemia, hypertension, and metabolic syndrome. Two reviewers independently extracted data on the study design, study quality, and study outcomes. Results We included 40 studies. Most studies showed that clozapine and olanzapine were associated with an increased likelihood of developing diabetes, while the results for risperidone and quetiapine were mixed. Although less well studied, ziprasidone and aripiprazole appeared to not be associated with the occurrence of diabetes. Information on antipsychotic-induced weight gain/obesity is extremely scarce. Regarding dyslipidemia, aripiprazole was not associated with an increased likelihood of developing dyslipidemia, clozapine was associated with an increased likelihood of developing dyslipidemia, and risperidone, olanzapine, quetiapine, and ziprasidone showed mixed results. Two studies suggested an association between ziprasidone and the occurrence of hypertension. Several studies found that the occurrence of a metabolic disorder acted as a risk factor for the development of other metabolic disorders. We did not find information on brexpiprazole, cariprazine, or lurasidone, and data on any long-acting SGA were lacking. Conclusion Although there are relevant differences among SGAs concerning the risk of metabolic disorders, it appears that none of the SGAs included in our review are fully devoid of these disturbances.Angelini Pharma Espana SL

Abnormal glycemic homeostasis at the onset of serious mental illnesses: A common pathway

Objective: Patients with serious mental illnesses exhibit a reduced lifespan compared with the general population, a finding that can not solely rely on high suicide risk, low access to medical care and unhealthy lifestyle. The main causes of death are medical related pathologies such as type 2 diabetes mellitus and cardiovascular disease; however pharmacological treatment might play a role. Material and methods: We compared a two hour glucose load in naïve patients at the onset of a serious mental illness (N = 102) (84 patients with a first episode of schizophrenia and related disorders, 6 with a first episode of bipolar I disorder and 12 with a first episode of major depression disorder) with another psychiatric diagnose, adjustment disorder (N = 17) and matched controls (N = 98). Results: Young patients with serious mental illness showed an increased two hour glucose load compared with adjustment disorder and the control group. Mean two hour glucose values [±standard deviation] were: for schizophrenia and related disorders 106.51 mg/dL [±32.0], for bipolar disorder 118.33 mg/dL [±34.3], for major depressive disorder 107.42 mg/dL [±34.5], for adjustment disorder 79.06 mg/dL[±24.4] and for the control group 82.11 mg/dL [±23.3] (p < 0.001). Conclusions: Our results reflect an abnormal metabolic pathway at the onset of the disease before any pharmacological treatment or other confounding factors might have taken place. Our results suggest a similar glycemic pathway in serious mental illnesses and the subsequent need of primary and secondary prevention strategies

Inverse association between negative symptoms and body mass index in chronic schizophrenia

BACKGROUND: We investigated whether negative symptoms, such as poor motivation or anhedonia, were associated with higher body mass index (BMI) in stable patients with schizophrenia chronically treated with antipsychotic medication. METHODS: 62 olanzapine- or clozapine-treated patients with illness duration of at least four years were selected from an international multicenter study on the characterization of negative symptoms. All participants completed the Brief Negative Symptom Scale (BNSS) and the Positive and Negative Syndrome Scale (PANSS). Bivariate correlations between BMI and negative symptoms (BNSS) were explored, as well as multiple regression analyses. We further explored the association of two principal component factors of the BNSS and BMI. Subsidiary analyses re-modeled the above using the negative symptoms subscale of the PANSS and the EMSLEY factor for negative symptoms for convergent validity. RESULTS: Lower negative symptoms (BNSS score) were associated with higher BMI (r=-0.31; p=0.015). A multiple regression analysis showed that negative symptoms (BNSS score) and age were significant predictors of BMI (p=0.037). This was mostly driven by the motivation/pleasure factor of the BNSS. Within this second factor, BMI was negatively associated with anhedonia (r=-0.254; p=0.046) and asociality (r=-0.253; p=0.048), but not avolition (r=-0.169; p=0.188). EMSLEY score was positively associated with BNSS (r=0.873, p<0.001), but negatively associated with BMI (r=-0.308; p=0.015). The association between PANSS and BMI did not reach significance (r=-224, p=0.080). CONCLUSIONS: We conclude that lower negative symptoms were associated with higher BMI (assessed using both the BNSS and EMSLEY) in chronic stable schizophrenia patients, mostly due to lower anhedonia and asociality levels

Women Undergoing Hormonal Treatments for Infertility: A Systematic Review on Psychopathology and Newly Diagnosed Mood and Psychotic Disorders

Background: The association between infertility treatments and mental disorders has been poorly addressed. This work aims to review current evidence on the psychopathological effects of hormonal treatments used for infertility on women and the occurrence of newly diagnosed mood and psychotic disorders. Methods: A systematic review was performed by searching PubMed and clinicaltrials.gov databases from inception until September 2019. Clinical trials on hormone treatments for infertility in patients with mood or psychotic disorders, as well as those evaluating the onset of symptoms, were included. Selected studies were published in English, Spanish, and Dutch language peer-reviewed journals. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Observational studies and case reports were excluded. Effect sizes for changes in depressive symptoms were calculated with Hedges'g and Cohen's d confidence intervals. A meta-analysis was not performed due to the heterogeneity of hormonal compounds in protocols. Results: From 1,281 retrieved records, nine trials were included; all of them were conducted in non-clinical populations. Four trials compared Gonadotropin-releasing hormone (GnRH) agonists and GnRH antagonists, showing a better mood profile for hormonal protocols including antagonists in one trial. Two trials compared protocols using GnRH agonists/antagonists versus natural cycle protocols (without gonadotropin stimulation), with a better mood profile (less depressive symptoms) in those protocols without gonadotropin stimulation. Other studies compared long and short protocols of GnRH agonists (no differences); two GnRH agonists, buserelin, and goserelin (no differences); and two patterns of clomiphene vs placebo administration (no differences). None of the selected studies investigated the risk of relapse in women with a previous diagnosis of depressive or psychotic disorders. When exploring pre-post changes in depressive symptoms, effect sizes suggested mild mood worsenings for most protocols (effect sizes ≤ -0.4), with the following pattern (worse to better): GnRH agonist > GnRH antagonist > no gonadotropin stimulation. Conclusions: This is the first systematic review exploring the psychopathological effects of hormonal infertility treatments. Our study suggests that protocols without gonadotropin stimulation show a better mood profile when compared to those using GnRH antagonists or GnRH agonists. Future studies need to include patients with major mood and psychotic disorders

Clozapine and paliperidone palmitate antipsychotic combination in treatment-resistant schizophrenia and other psychotic disorders: A retrospective 6-month mirror-image study

Background: Around 30% of patients with schizophrenia are considered treatment resistant (TRS). Only around 40% of TRS patients respond to clozapine. Long acting injectable antipsychotics could be a useful augmentation strategy for nonresponders. Methods: We conducted a multicenter, observational, naturalistic, retrospective, 6-month mirror-image study to evaluate the efficacy and tolerability of clozapine and paliperidone palmitate association in 50 patients with TRS and other psychotic disorders. Clinical outcomes and side effects were systematically assessed. Results: Six months after starting the combined treatment, participants showed a significant relief of symptoms, decreasing the Brief Psychiatric Rating Scale total score from 18.32 ± 7.71 to 7.84 ± 5.16 (p < 0.001). The number of hospitalizations, the length of hospital stays and the number of visits to emergency services also decreased, while an increase of the functionality was observed (Personal and Social Performance total score increased from 46.06 ± 118.7 to 60.86 ± 18.68, p < 0.001). There was also a significant decrease in the number and severity of side effects with the combination therapy, decreasing the Udvalg for Kliniske Undersogelser total score from 10.76 ± 8.04 to 8.82 ± 6.63 (p = 0.004). Conclusions: This study provides the first evidence that combining clozapine with paliperidone palmitate in patients with TRS and other psychotic disorders could be effective and safe, suggesting further research with randomized controlled trials of augmentation strategies for clozapine nonresponder patients. Policy Significance Statement: Patients with psychotic disorders such as schizophrenia show a variable response to antipsychotic treatments. Around 30% of patients are considered treatment resistant, indicated by insufficient symptom control to at least two different drugs. In these resistant cases, clozapine should be indicated, as it has shown to be superior to other options. However, only 40% of patients respond to clozapine, being necessary to establish which treatments could best potentiate clozapine action. Combining clozapine with long acting injectable antipsychotics, and particularly paliperidone palmitate, could be a useful strategy. We conducted a multicenter study of 50 patients with treatment-resistant schizophrenia and other psychotic disorders comparing the efficacy and tolerability in the 6 month-period prior and after starting the clozapine and paliperidone palmitate association. Our study suggests that this combination could be effective and safer, laying the groundwork for future clinical trials with this combination

Obstetric Phenotypes in the Heterogeneity of Schizophrenia.

Schizophrenia is a complex mental disorder with genetic and environmental components. Obstetric complications (OCs) are one of the most common environmental risk factors described. However, despite being different in timing and outcome, OCs are usually described as a homogeneous entity. In the present study, we evaluate the presence of different patterns of OCs evaluated with the Lewis-Murray Scale in chronic schizophrenia patients (n = 101) and their association with a crude marker of the intrauterine environment such as weight at birth.OCs related with abnormal fetal growth (p < 0.001) and OCs during gestation (p = 0.003) were associated with lower birth weight. However, difficulties in delivery, complications in pregnancy, and OCs all together (as a set) were not associated with weight at birth.Our results infer that OCs cannot be taken as a homogeneous group. Different patterns of OCs result in different birth weights, which is associated with specific metabolic, cognitive, and brain structure outcomes.This work was supported by the Government of Catalonia, Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (2014SGR441), with the grants FI-DGR-2013 Contract of the Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) (2015 FI_B2 00100) and from Fundació Bosch Gimpera (FBG) within the RETOS COLABORACIÓN 2015, funded by the Spanish Ministry of Economic Affairs and Competitiveness (RTC-2015-3440-1) to G. Mezquida. Dr. Bernardo has been supported by research funding from the Spanish Ministry of Health, the Spanish Ministry of Science and Education, the Spanish Ministry of Economic Affairs and Competitiveness, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), by Secretaria d'Universitat i Recerca del Departament d'Economia I Coneixement (2014SGR441), Foundation European Group for Research In Schizophrenia (EGRIS), and the 7th Framework Program of the European Union. Dr. Garcia-Rizo is supported by the PI14/00753 project, integrated into the State Plan of Scientific and Technical Research and Innovation 2013–2016 and co-financed by the ISCIII-General Evaluation Branch and the European Regional Development Fund (ERDF). Dr. Bobes is supported by the Spanish Ministry of Health, the Spanish Ministry of Science and Education, the Spanish Ministry of Economic Affairs and Competitiveness and CIBERSAM. Dr. Paz-Portilla has been also supported by the European Commission, ISCIII-General Evaluation Branch and CIBERSAM. Dr. Savulich is funded by a grant from Eton College and theWallitt Foundation. Dr. Fernanez-Egea is supported, in part, by the NIRH-Biomedical Research Center, Cambridge

Early treatment with JNJ-46356479, a mGluR2 modulator, improves behavioral and neuropathological deficits in a postnatal ketamine mouse model of schizophrenia.

Positive allosteric modulators of the metabotropic glutamate receptor 2 (mGluR2), such as JNJ-46356479 (JNJ), may mitigate the glutamate storm during the early stages of schizophrenia (SZ), which could be especially useful in the treatment of cognitive and negative symptoms. We evaluated the efficacy of early treatment with JNJ or clozapine (CLZ) in reversing behavioral and neuropathological deficits induced in a postnatal ketamine (KET) mouse model of SZ. Mice exposed to KET (30 mg/kg) on postnatal days (PND) 7, 9, and 11 received JNJ or CLZ (10 mg/kg) daily in the adolescent period (PND 35-60). Mice exposed to KET did not show the expected preference for a novel object or for social novelty, but they recovered this preference with JNJ treatment. Similarly, KET group did not show the expected dishabituation in the fifth trial, but mice treated with JNJ or CLZ recovered an interest in the novel animal. Neuronal immunoreactivity also differed between treatment groups with mice exposed to KET showing a reduction in parvalbumin positive cells in the prefrontal cortex and decreased c-Fos expression in the hippocampus, which was normalized with the pharmacological treatment. JNJ-46356479 treatment in early stages may help improve the cognitive and negative symptoms, as well as certain neuropathological deficits, and may even obtain a better response than CLZ treatment. This may have relevant clinical translational applications since early treatment with mGluR2 modulators that inhibit glutamate release at the onset of critical phases of SZ may prevent or slow down the clinical deterioration of the disease

Is bipolar disorder an endocrine condition? Glucose abnormalities in bipolar disorder

The World Health Organisation placed bipolar disorder at the top ten causes of disability worldwide, due not only to its functional impairment but also to its increased medical morbidity and mortality. An increased suicide rate, poor healthcare access, poor health habits, and medication side‐effects contribute to the increased morbidity and mortality. However, the leading contributors to the excess of mortality are cardiovascular pathologies 1, a finding already highlighted by Derby in 1933 in a cohort of manic‐depressive patients admitted to a general hospital. Cardiovascular risk factors, such as obesity, hypertension, type 2 diabetes mellitus (T2DM) 2, and lipid disturbances, are highly increased in bipolar disorder. In between those, glycemic abnormalities are the most repeated finding, taking into account that since the onset of the 20th century, several authors had raised the attention toward an unexpected relationship between manic‐depressive illness and glucose metabolism 3. In addition, the prevalence of T2DM in bipolar disorders ranges from 8% to 17% a threefold increase compared with the general population and bipolar patients with comorbid T2DM may have a more severe course of the psychiatric illness (greater number of depressive and manic episodes, more hospitalizations, and suicidality) and refractoriness to treatment. In addition, studies regarding metabolic disturbances in relatives of bipolar disorder and non‐affective psychosis have described an increased risk of developing glucose abnormalities, adding more scientific background to the unexpected relationship. However, pharmacological treatment, including both antipsychotic agents, antidepressants and mood stabilizers, may have confounded this relationship

Metabolic polygenic risk scores effect on antipsychotic-induced metabolic dysregulation: A longitudinal study in a first episode psychosis cohort

[EN] Objective: Metabolic syndrome is a health-threatening condition suffered by approximately one third of schizophrenia patients and largely attributed to antipsychotic medication. Previous evidence reports a common genetic background of psychotic and metabolic disorders. In this study, we aimed to assess the role of polygenic risk scores (PRSs) on the progression of the metabolic profile in a first-episode psychosis (FEP) cohort. Method: Of the 231 FEP individuals included in the study, 192-220 participants were included in basal analysis and 118-179 in longitudinal 6-month models. Eleven psychopathologic and metabolic PRSs were constructed. Basal and longitudinal PRSs association with metabolic measurements was assessed by statistical analyses.Results: No major association of psychopathological PRSs with the metabolic progression was found. However, high risk individuals for depression and cholesterol-related PRSs reported a higher increase of cholesterol levels during the follow-up (FDR <= 0.023 for all analyses). Their effect was comparable to other well-established pharmacological and environmental risk factors (explaining at least 1.2% of total variance).Conclusion: Our findings provide new evidence of the effects of metabolic genetic risk on the development of metabolic dysregulation. The future establishment of genetic profiling tools in clinical procedures could enable practitioners to better personalize antipsychotic treatment selection and dosage