Serum BDNF's Role as a Biomarker for Motor Training in the Context of AR-Based Rehabilitation after Ischemic Stroke

BACKGROUND: brain-derived neurotrophic factor (BDNF) may play a role during neurorehabilitation following ischemic stroke. This study aimed to elucidate the possible role of BDNF during early recovery from ischemic stroke assisted by motor training. METHODS: fifty patients were included after acute recovery from ischemic stroke: 21 first received classical rehabilitation followed by 'motor rehabilitation using motion sensors and augmented reality' (AR-rehabilitation), 14 only received AR-rehabilitation, and 15 were only observed. Serum BDNF levels were measured on the first day of stroke, on the 14th day, before AR-based rehabilitation (median, 45th day), and after the AR-based rehabilitation (median, 82nd day). Motor impairment was quantified clinically using the Fugl-Meyer scale (FMA); functional disability and activities of daily living (ADL) were measured using the Modified Rankin Scale (mRS). For comparison, serum BDNF was measured in 50 healthy individuals. RESULTS: BDNF levels were found to significantly increase during the phase with AR-based rehabilitation. The pattern of the sequentially measured BDNF levels was similar in the treated patients. Untreated patients had significantly lower BDNF levels at the endpoint. CONCLUSIONS: the fluctuations of BDNF levels are not consistently related to motor improvement but seem to react to active treatment. Without active rehabilitation treatment, BDNF tends to decrease

Cortisol and DHEAS Related to Metabolic Syndrome in Patients with Schizophrenia

Background: Both dehydroepiandrosterone (DHEAS) and cortisol are secreted by the adrenal glands and may modulate metabolic syndrome (MetS), which often affects the health of patients with schizophrenia. The relationship between the serum levels of these hormones and MetS has not been established. Purpose: In this pilot study, we investigated the serum levels in schizophrenia patients with and without MetS and compared them with those in healthy volunteers. Patients and Methods: After obtaining informed consent, 110 patients with acute paranoid schizophrenia were recruited directly after admission to the Mental Health Research Institute. The control group consisted of 51 persons reported on questioning to be mentally and somatically healthy. Blood samples to prepare serum were drawn after an 8-h overnight fast during one of the first days of admission. Serum cortisol and DHEAS concentrations were quantified by enzyme-linked immunosorbent assay. Results: A total of 42 patients had MetS and 68 patients were without MetS. The cortisol blood level was significantly (p = 0.012) higher in schizophrenia patients without MetS in comparison to healthy controls, while patients with schizophrenia and a MetS have significantly (p = 0.014) lower DHEAS levels than healthy volunteers. These differences could, however, exclusively be attributed to female participants. Analysis of covariance adjusted for gender and age demon-strated a significant relationship between age and DHEAS levels (F = 9.512, р =0.003). Conclusion: Lower DHEAS serum levels in relationship to MetS become evident in women, but not in men, and have age differences as a confounding factor

Adipocytokines and Metabolic Syndrome in Patients with Schizophrenia

The adipokines leptin, adiponectin, tumor necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) might be associated with metabolic syndrome (MetS) in patients with schizophrenia. In the present study, we attempted to confirm the results of previous reports and assessed their MetS-related correlation with body fat composition and biochemical parameters. We measured in 46 patients with schizophrenia and MetS serum levels of adiponectin insulin, leptin, TNF-alpha and IL-6 and compared these levels to those of patients with schizophrenia without MetS. The MetS patients had significantly increased leptin levels and leptin/adiponectin ratios, as well as decreased adiponectin levels. Leptin levels correlated with several metabolic parameters, both in patients with and without MetS, including body fat percentage, total fat fold, and body mass index (BMI). Patients without abnormal MetS components had lower levels of leptin and leptin/adiponectin ratios compared with patients who had one or two MetS components. Leptin/adiponectin ratios were higher in patients who had four rather than three MetS components. Multiple regression analysis revealed multiple associations for leptin but only one for adiponectin, TNF-alpha, and IL-6. Our results support an important pathophysiological role for leptin more than adiponectin in patients with schizophrenia with MetS

Cytokine Level Changes in Schizophrenia Patients with and without Metabolic Syndrome Treated with Atypical Antipsychotics

The present study aims at comparing the change in cytokine levels in schizophrenia patients treated with atypical antipsychotics, with or without metabolic syndrome (MetS). The study included 101 patients with schizophrenia, 38 with and 63 without MetS, who received risperidone, quetiapine, olanzapine or aripiprazole for six weeks. We analyzed the concentration of 21 cytokines in the serum patients. The treatment with atypical antipsychotics changed some proinflammatory cytokine levels. It led to increased IFN-alpha 2 (p = 0.010), IL-1 alpha (p = 0.024) and IL-7 (p = 0.017) levels in patients with MetS, whereas the same treatment led to decreased levels of IFN-gamma (p = 0.011), IL-1 beta (p = 0.035), IL-12p40 (p = 0.011), IL-17A (p = 0.031), IL-6 (p = 0.043) and TNF-alpha (p = 0.012) in individuals without MetS. Our results demonstrated the effects of atypical antipsychotics on the immune-inflammatory parameters, depending on the metabolic disturbances in schizophrenia patients

Association of ANKK1 polymorphism with antipsychotic-induced hyperprolactinemia

Objective: Schizophrenia is a severe highly heritable mental disorder. Genetic polymorphisms of dopaminergic pathways are related to pathogenesis of drug response. Hyperprolactinemia (HPRL), a common adverse effect of antipsychotics, is attributed to blockade of dopamine D2 receptors. Ankyrin Repeat and Kinase Domain containing 1 (ANKK1) gene is closely related to Dopamine Receptor D2 type (DRD2) gene functioning. We examined whether the functional polymorphism rs2734849 in the ANKK1 gene is associated with antipsychotic-induced HPRL. Methods: We recruited 446 patients with schizophrenia from among the Russian population of the Siberian region. The polymorphism rs2734849 in the ANKK1 gene was genotyped with The MassARRAY® Analyzer 4 by Agena Bioscience™, using the kit SEQUENOM Consumables iPLEXGold 384. Genotype and allele frequencies were compared between groups of schizophrenia patients with and without HPRL using the χ2 test. Results: A comparison between schizophrenia patients with and without HPRL revealed significantly higher frequency of the C allele of the polymorphic variant rs2734849 in the ANKK1 gene in patients with HPRL as compared to the patients without it (χ2 = 3.70; p =.05; odds ratio [OR] = 1.30 [0.99–1.69]). Conclusion: The functional polymorphism rs2734849 in the ANKK1 gene was associated with HPRL in patients with schizophrenia

COMT gene polymorphism and antipsychotic-induced hyperprolactinemia in schizophrenia patients

Hyperprolactinemia (HPRL) is considered to be a frequent and typical adverse drug reaction caused by antipsychotic medications first and foremost due to excessive dopamine D2 receptors blockade. The aim is to study the set of polymorphisms of genes encoding neurotransmitter synthesis and metabolism enzymes COMT, TPH1 and TPH2 in schizophrenia inpatients. A comprehensive examination of 446 schizophrenia inpatients, aged 18-75 years, was conducted. Genotyping of DNA samples in patients with or without HPRL was carried out for 14 polymorphisms of COMT, TPH1, and TPH2 genes. We revealed an association between carriership of the COMT rs165774* G allele and HPRL. As a result of the study, a regression model was designed to predict the risk of developing HPRL in schizophrenia inpatients, taking into account age, gender, and treatment duration, the dosage of drugs in chlorpromazine equivalents as independent covariates and genotypes of the studied polymorphisms

Beta-Endorphin and Oxytocin in Patients with Alcohol Use Disorder and Comorbid Depression

Background: The neuropeptides β-endorphin and oxytocin are released into the bloodstream as hormones from the pituitary gland but also have an important function as neuroregulators in the forebrain. The blood levels of both polypeptides have been shown to reflect depressive symptoms. β-Endorphin, in particular, is also involved in abstinence from alcohol. Methods: The serum levels of β-endorphin and oxytocin were measured during the early withdrawal phase in patients with alcohol use disorder (AUD) with (N = 35) or without (N = 45) depressive comorbidity and compared with those in healthy volunteers (N = 23). In addition to comparing the groups, the study examined whether serum levels correlated with various psychometric measures of dependence, depression and aggression, as well as with clinical characteristics of dependence. Results: Both serum levels of beta-endorphin and oxytocin were significantly lower in patients than those in healthy controls (p = 0.011 for β-endorphin and p = 0.005 for oxytocin, Kruskal–Wallis test). In patients with depressive comorbidity, the significance was greatest (p = 0.005 for β-endorphin and p = 0.004 for oxytocin, U-test). There was no correlation with clinical or psychometric parameters (p > 0.05, Spearman test), but beta-endorphin levels did correlate significantly with physical aggression (p = 0.026, Spearman test). Conclusions: Serum levels of β-endorphin and oxytocin are lower in patients with AUD, particularly in those with depressive comorbidity. β-Endorphin levels correlated with physical aggression according to the Buss–Durkee (BDHI) estimates

Association of Cholinergic Muscarinic M4 Receptor Gene Polymorphism with Schizophrenia

Background: Previous studies have linked muscarinic M4 receptors (CHRM4) to schizophrenia. Specifically, the rs2067482 polymorphism was found to be highly associated with this disease. Purpose: To test whether rs2067482 and rs72910092 are potential risk factors for schizophrenia and/or pharmacogenetic markers for antipsychotic-induced tardive dyskinesia. Patients and Methods: We genotyped DNA of 449 patients with schizophrenia and 134 healthy controls for rs2067482 and rs72910092 polymorphisms of the CHRM4 gene with the use of the MassARRAY® System by Agena Bioscience. Mann–Whitney test was used to compare qualitative traits and χ2 test was used for categorical traits. Results: The frequency of genotypes and alleles of rs72910092 did not differ between patients with schizophrenia and control subjects. We did not reveal any statistical differences for both rs2067482 and rs72910092 between schizophrenia patients with and without tardive dyskinesia. The frequency of the C allele of the polymorphic variant rs2067482 was significantly higher in healthy persons compared to patients with schizophrenia (OR=0.51, 95% CI [0.33–0.80]; p=0.003). Accordingly, the CC genotype was found significantly more often in healthy persons compared to patients with schizophrenia (OR=0.49, 95% CI [0.31–0.80]; p=0.010). Conclusion: Our study found the presence of the minor allele (T) of rs2067482 variant being associated with schizophrenia. We argue that the association of rs2067482 with schizophrenia may be via its regulatory effect on some other gene with protein kinase C and casein Kknase substrate in neurons 3 (PACSIN3) as a possible candidate. Neither rs2067482 nor rs72910092 is associated with tardive dyskinesia