THE EFFECT OF SELECTED POLYMORPHISMS OF THE DOPAMINE RECEPTOR GENE DRD2 AND THE ANKK-1 ON THE PREFERENCE OF CONCENTRATIONS OF SUCROSE SOLUTIONS IN MEN WITH ALCOHOL DEPENDENCE

Background: The aim of the study was to determine the influence of DRD2 gene polymorphisms in exon 8 G/A (rs 6276) in the promoter region -141 C Ins/Del (rs1799732) and the influence of ANKK-1 gene Taq-1A polymorphism (rs 1800497) on the preference of increasing sucrose concentrations in men with alcohol dependence. Subjects and methods: 63 male patients with alcohol dependence were genotyped for the above polymorphisms. Their preference for increasing sucrose concentrations was tested and their taste intensity perception of sucrose solutions was assessed. The patients were tested with the \u27Sniffin\u27 Sticks\u27 olfactory test. Results: We found a statistically significant association between some alleles of ANKK 1 gene Taq 1A polymorphisms and sucrose preference in the subjects. The A1 Taq 1A allele determined hedonistic response to the two highest concentrations of sucrose. No association was found regarding the other two polymorphisms (in the promoter region and in the exon 8 of the DRD2 gene). Conclusions: Study results suggest Taq-1A polymorphism plays a role in the preference to high concentrations of sucrose and its potential association with alcohol dependence pathogenesis

Neonatal Administration of Thimerosal Causes Persistent Changes in Mu Opioid Receptors in the Rat Brain

Thimerosal added to some pediatric vaccines is suspected in pathogenesis of several neurodevelopmental disorders. Our previous study showed that thimerosal administered to suckling rats causes persistent, endogenous opioid-mediated hypoalgesia. Here we examined, using immunohistochemical staining technique, the density of μ-opioid receptors (MORs) in the brains of rats, which in the second postnatal week received four i.m. injections of thimerosal at doses 12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate putamen and hippocampus were examined. Thimerosal administration caused dose-dependent statistically significant increase in MOR densities in the periaqueductal gray and caudate putamen, but decrease in the dentate gyrus, where it was accompanied by the presence of degenerating neurons and loss of synaptic vesicle marker (synaptophysin). These data document that exposure to thimerosal during early postnatal life produces lasting alterations in the densities of brain opioid receptors along with other neuropathological changes, which may disturb brain development

Catechol-O-Methyltransferase Val158Met Polymorphism and Clinical Response to Antipsychotic Treatment in Schizophrenia and Schizo-Affective Disorder Patients: a Meta-Analysis

BACKGROUND: The catechol-O-methyltransferase (COMT) enzyme plays a crucial role in dopamine degradation, and the COMT Val158Met polymorphism (rs4680) is associated with significant differences in enzymatic activity and consequently dopamine concentrations in the prefrontal cortex. Multiple studies have analyzed the COMT Val158Met variant in relation to antipsychotic response. Here, we conducted a meta-analysis examining the relationship between COMT Val158Met and antipsychotic response. METHODS: Searches using PubMed, Web of Science, and PsycInfo databases (03/01/2015) yielded 23 studies investigating COMT Val158Met variation and antipsychotic response in schizophrenia and schizo-affective disorder. Responders/nonresponders were defined using each study's original criteria. If no binary response definition was used, authors were asked to define response according to at least 30% Positive and Negative Syndrome Scale score reduction (or equivalent in other scales). Analysis was conducted under a fixed-effects model. RESULTS: Ten studies met inclusion criteria for the meta-analysis. Five additional antipsychotic-treated samples were analyzed for Val158Met and response and included in the meta-analysis (ntotal=1416). Met/Met individuals were significantly more likely to respond than Val-carriers (P=.039, ORMet/Met=1.37, 95% CI: 1.02-1.85). Met/Met patients also experienced significantly greater improvement in positive symptoms relative to Val-carriers (P=.030, SMD=0.24, 95% CI: 0.024-0.46). Posthoc analyses on patients treated with atypical antipsychotics (n=1207) showed that Met/Met patients were significantly more likely to respond relative to Val-carriers (P=.0098, ORMet/Met=1.54, 95% CI: 1.11-2.14), while no difference was observed for typical-antipsychotic-treated patients (n=155) (P=.65). CONCLUSIONS: Our findings suggest that the COMT Val158Met polymorphism is associated with response to antipsychotics in schizophrenia and schizo-affective disorder patients. This effect may be more pronounced for atypical antipsychotics.C.C.Z. is supported by the Brain and Behavior Research Foundation, American Foundation for Suicide Prevention and Eli Lilly. D.F. is supported by the Vanier Canada Graduate Scholarship. D.J.M. has been or is supported by the Canadian Institute of Health Research (CIHR) Operating Grant: “Genetics of antipsychotic-induced metabolic syndrome,” Michael Smith New Investigator Salary Prize for Research in Schizophrenia, NARSAD Independent Investigator Award by the Brain & Behavior Research Foundation, and Early Researcher Award from Ministry of Research and Innovation of Ontario. E.H. is supported by the Canada Graduate Scholarship. H.Y.M. has grant support from Sumitomo Dainippon, Sunovion, Boehringer Ingelheim, Eli Lilly, Janssen, Reviva, Alkermes, Auspex, and FORUM. J.A.L. has received research funding from Alkermes, Biomarin, EnVivo/Forum, Genentech, and Novartis. J.L.K. is supported the CIHR grant “Strategies for gene discovery in schizophrenia: subphenotypes, deep sequencing and interaction.” J.R.B. is supported by NIH grant MH083888. A.K.T. is supported by a NARSAD Young Investigator Award. J.S. is supported by a Pfizer independent grant. P.M. receives salary from Clinica Universidad de Navarra and has received research grants from the Ministry of Education (Spain), the Government of Navarra (Spain), the Spanish Foundation of Psychiatry and Mental Health, and Astrazeneca. S.G. is supported by the Ningbo Medical Technology Project Fund (No. 2004050), the Natural Science Foundation of Ningbo (No. 2009A610186, No. 2013A610249), and the Zhejiang Provincial Medical and Health Project Fund (No. 2015127713). S.G.P. has received research support from Otsuka, Lundbeck, FORUM, and Alkermes

Intergenerational implications of alcohol intake: metabolic disorders in alcohol-naïve rat offspring

Alcohol drinking may be associated with an increased risk of various metabolic diseases. Rat lines selectively bred for alcohol preference and alcohol avoidance constitute an interesting model to study inherited factors related to alcohol drinking and metabolic disorders. The aim of the present study was to compare the levels of selected laboratory biomarkers of metabolic disorders in blood samples from naïve offspring of Warsaw alcohol high-preferring (WHP), Warsaw alcohol low-preferring (WLP), and wild Wistar rats. Blood samples were collected from 3-month old (300–350 g) alcohol-naïve, male offspring of WHP (n = 8) and WLP rats (n = 8), as well as alcohol-naïve, male, wild Wistar rats. Markers of metabolic, hepatic, and pancreatic disorders were analysed (levels of homocysteine, glucose, total cholesterol, triglycerides and γ-glutamyl transferase (GGT), aspartate (AST), alanine aminotransferase (ALT), and amylase serum activities). Alcohol-naïve offspring of WHP, WLP, and wild Wistar rats differed significantly in the levels of triglycerides, total cholesterol, homocysteine, as well as in the activity of GGT, ALT, AST, and amylase enzymes. Most markers in the alcohol-naïve offspring of WHP rats were altered even thought they were never exposed to alcohol pre- or postnatally. This may suggest that parental alcohol abuse can have a detrimental influence on offspring vulnerability to metabolic disorders

Recommendations for the prevention and treatment of postpartum depression

Epidemiological data clearly indicate that depression is becoming an increasingly important health and social problemtoday. According to the World Health Organization (WHO), depression currently affects 350 million people worldwide andis considered the second most common cause of disability in Europe after ischemic heart disease. It is estimated that thishealth problem may affect as many as five million people in Poland. The gap between the reported number of patientstreated and the prevalence of depression, highlights the scale of unmet needs. With the limited availability of specialistsin psychiatric care, the most appropriate measures seem to be those aimed at increasing the competence of doctors ofother specialties in the diagnosis and treatment of depression. Early detection and treatment results in faster remission,reduces relapses and mortality.The recommendations concerning prevention of depression were commissioned by the Polish Ministry of Health as a part ofthe Depression Prevention Program for 2016–2020. The Program has developed recommendations addressed to specialistsin various fields of medicine, other than psychiatry, focusing on three risk groups: children and adolescents, women in theperinatal period and the elderly. These recommendations focus on the management of suspected postpartum depressionand provide specific guidelines for medical staff having contact with pregnant and postpartum women (gynecologists,midwives, pediatricians)

Cost of relapse management in patients with schizophrenia in Italy and Spain: comparison between lurasidone and quetiapine XR

Background and Objective: Schizophrenia is a low-prevalence mental disorder with a global age-standardized prevalence of 21 million people (2016). Second-generation antipsychotics (lurasidone and quetiapine XR) are recommended as the first-line treatment for schizophrenia. It is interesting to investigate how the results of clinical studies translate into direct medi-cal costs. The objective of this analysis was to assess the direct medical costs related to pharmaceutical treatments and the management of relapses in patients affected with schizophrenia treated with lurasidone (74 mg) vs quetiapine XR (300 mg) assuming the Italian and Spanish National Health Service perspective. Methods: A health economic model was developed based on a previously published model. The analysis considered direct medical costs related to the pharmacological therapies and inpatient or outpatient management of relapses (direct medical costs referred to 2019). The probability of relapses and related costs were derived from two systematic reviews. A determin-istic sensitivity analysis was implemented to test the robustness of the results. Results: The use of lurasidone (74 mg) compared with quetiapine XR (300 mg) would lead to a reduction in direct medical costs in Italy and Spain, with a lower cost per patient of − 163.7 € (− 9.0%) and − 327.2 € (− 22.7%), respectively. In detail, it would lead to an increase in the cost of therapy of + 53.8% and of + 30.5% in Italy and Spain, respectively, to a decrease in the cost of relapses with hospitalization of − 135.7%, and to an increase in the cost of relapses without hospitalization of + 24.5%. Conclusions: The use of lurasidone (74 mg) for the treatment of patients affected with schizophrenia, compared with quetia-pine XR (300 mg), would be a cost-saving strategy in the two contexts investigated assuming the National Health Service point of view