Serum Of Schizophrenic Patients Research Articles

Effects of Quetiapine on Thyroid Function Tests in Schizophrenic Patients

To investigate the effects of quetiapine on thyroid function tests in newly diagnosed schizophrenic patients. Thirty subjects with schizophrenia, were treated openly with quetiapine .Diagnosis of schizophrenia was made according to DSM-IV criteria of American Psychiatric Association. Another thirty healthy individual participated in the study as a control group. Thyroid data, consisting of values for thyroid-stimulating hormone (TSH), total triiodothyronine (TT3 ), and total thyroxine (TT4). TSH, TT3, and TT4 were measured by radioimmunoassay. Measurements of patient’s thyroid data were done before and after 3 months of therapy (Suggested period of the research) with quetiapine and at the start of the research for the controls. Comparison of TSH, TT3 and TT4 of the control group and those of patients before treatment shows a non significant differences for all parameters. Comparison between TSH, TT3 and TT4 values before and after treatment with quetiapine shows only a significant reduction of TT4 values (P<0.001). This study shows that 3 months therapy with quetiapine leads to a reduction of TT4 concentration in the serum of schizophrenic patients.

Correlation between latent toxoplasmosis and thyroid hormone levels in sera of schizophrenic patients

Latent toxoplasmosis is a prevalent chronic infection caused by a protozoan parasite called Toxoplasma gondii. Recent studies have shown that T. gondii may affect thyroid hormone levels and thus induce behavioral alteration. However, this correlation has been inadequately investigated. Therefore, we aimed to examine the relationship between latent toxoplasmosis and thyroid hormone levels in schizophrenic patients. For this purpose, blood samples and sociodemographic information were collected from 101 schizophrenic patients attending three psychiatric hospitals in Kurdistan region of Iraq. Anti-T. gondii-IgG antibodies and thyroid hormones levels (TSH, T3, T4) were determined in sera of all patients using ELISA technique. Anti-T. gondii-IgG antibodies were detected in sera of 40 (39.6%) out of 101 schizophrenic patients. Logistic regression analysis showed significant association between toxoplasmosis and schizophrenic patients in 50-60 age group (OR=6.177, p=0.05), and un-employed patients (OR=3.562, p=0.05). Data analysis showed non-significant difference in TSH levels between IgG seropositive and IgG seronegative group (p>0.05). On the other hand, T4 levels were significantly higher in the seropositive (10.16 ± 2.61) than seronegative group (7.01 ± 2.01), with highly significant positive correlation between IgG and T4 levels (p= 0.001). Finally, T3 levels were significantly higher in the seropositive (1.91 ± 0.5) than seronegative group (1.12 ± 0.43), with non-significant positive correlation between IgG and T3 levels (p=0.30). Owing to the fact that there was statistically significant increase in thyroid hormone levels in T. gondii seropositive patients, our results suggest that there is a significant association between toxoplasmosis and thyroid hormone levels in schizophrenic patients.

Marker of schizophrenia with enduring negative symptoms

IntroductionThe relevance of this study is determined by the need to search for biological markers of schizophrenia. The detection and validation of such molecules can become the basis for the creation of additional paraclinical diagnostic methods or contribute to the creation of targets for individual pharmacotherapy, which is an important task of modern fundamental medicine.ObjectivesComparative proteomic analysis of serum in schizophrenic patients with positive and negative symptoms.MethodsThe study includes 10 healthy donors and 27 patients with schizophrenia. Samples preparation included: serum purification from major proteins via affinity chromatography, 1D-PAGE proteins separation, in-gel tryptic hydrolysis, LC-MS/MS mass-spectrometry (Orbitrap Q-exactive HF mass spectrometer, Agilent Technologies). Identification of proteins was carried out using Mascot software Ver. 2.1 («Matrix Science», USA). Proteins for quantitative analysis were selected in view of the DISGENET database. Quantitative LC-MS-SRM analysis of selected protein was performed on QQQ TSQ Vantage (Thermo Scientific) with labeled peptide standards.ResultsReceptor-interacting serine/threonine-protein kinase 1 was selected for quantitative assessment. Significant differences were revealed in the RIPK1 concentrations in the serum of schizophrenic patients with negative and positive symptoms (p=0.02). The serum concentration of RIPK1 in patients with negative symptoms is tenfold in patients with positive symptoms.ConclusionsReceptor-interacting serine/threonine-protein kinase 1 can be considered a biomarker of negative symptoms of schizophrenia based on a significant increase in serum concentration. Mass spectrometric analysis was carried out of the “Human Proteome” Core Facility of the Institute of Biomedical Chemistry Moscow. Support by Grant of RSF № 18-15-00053P.DisclosureNo significant relationships.

Investigation of anti-NMDA receptor antibodies in first episode psychosis patients

IntroductionAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune limbic encephalitis, where psychiatric symptoms are often the initial presentation dominant initially. These patients are mainly admitted to psychiatric wards, due to first episode psychosis (FEP).ObjectivesMultiple studies analysed whether anti-NMDAR antibodies were present in the sera of schizophrenic patients, but results have not verified this hypothesis. It is possible, however, that unknown autoimmune antibodies play a role in FEP, similarly to anti-NMDAR antibodies.Methods40 patients with FEP and 30 healthy controls have been recruited to the study. Patients with affective psychosis, drug-related psychosis and patients with diagnosed encephalitis were excluded. The sera were tested with immune fluorescent assays for anti-NMDAR antibodies. A non-specific method was used to test anti-brain antibody activity on monkey-cerebellum and rat-hippocampus slices.ResultsNeither the samples from the 40 patients, nor the samples of healthy controls contained anti-NMDAR antibodies. 14 of the patients’ and only 6 of the healthy controls’ serum showed positive reaction of the neuroendothelium. These results suggest that there is a difference between the groups, although the results are not significant.ConclusionsNone of the 40 patients proved positive for anti-NMDAR antibodies in agreement with previous studies. However, a higher proportion of samples from the FEP group showed activity in the neuroendothelium of non-specific immune fluorescent assays compared to healthy controls. Based on literature and on our experience, it is possible, that unknown autoimmune antibodies play role in FEP.DisclosureNo significant relationships.

Comparison between Interleukin-2 Serum Levels and Positive and Negative Syndrome Scale Scores of Schizophrenia Patients that Received Haloperidol with Risperidone Therapy

BACKGROUND: There is a possibility of interleukin-2 (IL-2) being involved in the pathophysiology of Schizophrenia. The increase of IL-2 levels has been discovered in the serum of schizophrenic patients in earlier studies. An amount of antipsychotic has been associated with the decrease of IL-2. AIM: Therefore, this study was intended to compare the serum IL-2 levels of schizophrenic patients who received Haloperidol therapy with patients who received Risperidone as well as examine the relationship between serum IL-2 levels with the positive and negative syndrome scale (PANSS) score of schizophrenic patients receiving Haloperidol and Risperidone therapy. METHODS: This study is an observational study with a prospective cohort design consisting of 36 patients who have met the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria for Schizophrenic patients who did not take antipsychotic drugs for 2 weeks and were hospitalized at the Special Hospital of South Sulawesi Province. Afterwards, the patients were grouped into two groups, where each group consisted of 18 people, namely, the group of patients who received Haloperidol and the group of patients who received Risperidone, and then were furtherly evaluated until the 4th week. The sample examination method used was enzyme-linked immunosorbent assay to see the blood serum IL-2 levels. Clinical symptoms of Schizophrenia were assessed using the PANSS score. RESULTS: The study showed that serum IL-2 levels decreased at the 4th week after conducting antipsychotic therapy among both groups. The decrease in PANSS scores in the Risperidone group was greater compared to the Haloperidol group at week 3 and week 4. In the serum IL-2 levels difference of the group who received Risperidone therapy, the decrease was greater than those receiving Haloperidol therapy (3.72 ± 1.30 ng/ml vs. 2.43 ± 1.39 ng/ml, p = 0.008). In addition, based on the correlation test, no significant correlation was present between the difference in the total PANSS score and the difference in the serum IL-2 levels within the Haloperidol group (p = 0.059, r = 0.453) and the Risperidone group (p = 0.518, r = 0.113). Schizophrenic patients have higher serum IL-2 levels than healthy people. Schizophrenic patients who received antipsychotics for 4 weeks experienced a decrease in serum IL-2 levels. Risperidone administration had a higher decrease in serum IL-2 levels than Haloperidol. CONCLUSION: Changes in serum IL-2 levels as a consideration of one of the Biomarkers are still needed for further evaluation. The therapeutic role of Haloperidol and Risperidone can be attributed as anti-inflammatory in Schizophrenia but cannot be attributed to improvement in the psychopathological status of Schizophrenic patients.

Apolipoprotein serum levels related to metabolic side effects in patients with schizophrenia

In the general population, metabolic syndrome (MetS) is associated with a 4 times relative risk of developing diabetes and approximately a 2-fold risk of coronary heart disease, stroke, and premature mortality [1]. In patients with schizophrenia the overall rate of MetS is 32.5% [1]. This contributes to having an average mortality rate that is 2-3 times higher than the general population, corresponding to a 10-25 year shortened life expectancy [2]. Antipsychotics are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus [2,3]. Use both of classical conventional and modern atypical neuroleptics have been associated with metabolic disturbances; so drug-induced metabolic disturbances are observed in 39.0% of patients taking haloperidol, 44.0% - clozapine, 22.0% - aripiprazole, 33.3% - amisulpride, 34.0% - olanzapine, 35.0% – risperidone [4]. Therefore, an ongoing need exists for reliable predictors of metabolic risks in individual patients indicated for antipsychotic treatment. Apolipoproteins and cholesterol play a critical role in synapse and myelin maintenance as well as integrity and may thus be both appealing candidates in the pathogenesis of schizophrenia and biomarkers of antipsychotic induce side metabolic effects [5]. The aim of this study is to investigate serum apolipoproteins concentration in schizophrenic patients with or without metabolic syndrome and healthy donors. Methods: The study was carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments involving humans. After obtaining approval of the study protocol by the local ethical committee, suitable participants were recruited from psychiatric hospitals. We included 53 patients with diagnosis of paranoid schizophrenia verified according to the International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10: F20). Patients have been divided into two groups with and without MetS according to criteria the International Diabetes Federation (2005). All patients received antipsychotic treatment. The control group included 20 mentally and physically healthy subjects. Serum apolipoproteins A1, C3, E, A2 and C2 were measured using xMAP technology (Luminex). Statistical analysis was performed by SPSS version 20.0. Results: We found a significant decrease in the concentration of apolipoprotein A1 in the serum of schizophrenic patients with a MetS (p = 0.002) and no side effects (p = 0.013) compared with the control group. The level of ApoC3 (p = 0.001) and ApoC2 (p = 0.002) were increased in patients with schizophrenia with MetS in comparison with the control group and patients without MetS. No other significant differences were established concerning the other assayed apolipoproteins. Conclusions: Literature date and our results suggest that disturbances in level of Apo A1 play role in pathogenesis of schizophrenia while level of ApoC3 and ApoC2 can reflect the metabolic disbalance and could be a novel biomarker to predict metabolic side effects associated with antipsychotic treatment. Future studies with a larger sample size, a well-defined control group, a longer study time duration could be of great clinical utility, when these can predict antipsychotic-associated metabolic problems in patients that carry a higher cardiovascular risk. Disclosure statement: This work is supported by RSF grant N 18-15-00011

Investigation of schizophrenic patients from Istanbul, Turkey for the presence of West Nile virus

Association of some neurotropic viruses like Borna Disease virus and Herpes virus with schizophrenia is better explained. However, the role of West Nile virus (WNV) infection in schizophrenia is not well documented. Therefore, this study was performed to investigate possible association between schizophrenia and presence of antibodies and WNV RNA in schizophrenic patients. For this, 200 blood samples from patients with schizophrenia and 200 from control groups were collected in Istanbul, Turkey. WNV RNA was not detected in any of the 200 patients and 200 controls analyzed by real-time RT-PCR. One hundred and twelve sera of schizophrenic patients and 162 of controls were analyzed for the presence of IgG antibodies to WNV by a commercial IgG-ELISA (Euroimmun, Germany). Antibodies to WNV were detected in 6 schizophrenic patients and 5 controls. ELISA positive patients had antipsychotic therapy. The difference between groups in terms of seropositivity to WNV was not statistically significant (p = 0.887, p = 0.148). Known symptoms of schizophrenia were observed in these patients, and interestingly majority had close contact to cats in the past and come from agricultural area of Turkey where potential area of mosquitoes and bird habitat. In conclusion, the results of this study show that antibodies to WNV in people do not seem to be associated with schizophrenia. However, detecting antibodies to WNV in schizophrenic patients suggests that WNV infection should be considered in endemic areas as it may play role in psychiatric diseases.

Correlation of adenosinergic activity with superior efficacy of clozapine for treatment of chronic schizophrenia: a double blind randomised trial

It has been proposed that a deficit of adenosinergic activity could contribute to the pathophysiology of schizophrenia. The authors undertook this study to further evaluate the level of adenosine deaminase (ADA) in patients with chronic schizophrenia treated with monotherapy of haloperidol, risperidone or clozapine and correlation between the ADA level with response to treatment. The trial was a prospective, 8-week, double blind study of parallel groups of patients with chronic schizophrenia. Eligible participants in the study were 51 patients with chronic schizophrenia with ages ranging from 20 to 45 years. All participants were inpatients, in the active phase of illness, and met DSM-IV-TR criteria for schizophrenia. Patients were randomly allocated (17 patients in each group) to risperidone (6 mg/day) or haloperidol 15 mg/day or clozapine (300 mg/day). Serum ADA activity was measured at baseline and week 8. The plasma levels of ADA in patients with chronic schizophrenia who received clozapine were significantly higher than patients who received haloperidol. In addition, response to treatment was positively correlated with plasma levels of ADA only in the clozapine group (r = 0.46 and p = 0.04). The results indicate an increased activity of the enzyme ADA in the serum of schizophrenic patients being treated with clozapine and this increase may be correlated with clozapine's superior antipsychotic efficacy.

Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part II: Adult Subjects

Background: In our preceding study, we assayed in a blind fashion the blood sera of young normal subjects and schizophrenic patients for levels of platelet autoantibodies (PAA). The recorded PAA titers of the schizophrenic patients were significantly higher than those of the normal subjects. This observation has lent support to this test being used as an objective evaluation of schizophrenia in young subjects in the future. In addition, this finding strongly suggested that the etiology of a distinct group of sufferers of this disorder could have originated from an autoimmune reaction against platelets which can, under certain conditions, cross-react with brain tissue. Aims: In the present study, PAA titers in the sera of adult schizophrenic patients and matched normal subjects were determined analogously to the preceding study. The effect of hospitalization and drug treatments on the apparent blood test scoring in adult subjects could thus be evaluated. Methods: A total of 46 schizophrenia patients (30 men and 16 women) aged 19–45 years (mean ± SD: 31.7 ± 8.0 years) with a minimum score of 60 on the Positive and Negative Symptom Scale and 43 healthy control subjects (22 men and 21 women) aged 21–44 years (mean ± SD: 31.9 ± 6.9 years) participated in the study. The blood titers of PAA were evaluated in a single-blind fashion using an optimized ELISA test scored by optical density (OD) units. A positive test was defined as a value above 1.3 OD units. Results: The titers of PAA in the group of schizophrenic patients (1.1 ± 0.55 OD units, range: 0.360–2.285 OD units) were significantly higher in comparison to those of the healthy control subjects (0.81 ± 0.37 OD units, range: 0.360–1.704 OD units; p = 0.004, two-tailed unpaired t-test). Significantly more schizophrenic patients showed a positive test (15 patients out of 46) than the control subjects (5 out of 43). However, significantly higher OD values of 1.55 ± 0.5 were recorded in the group of patients with less than 3 years of registered disease (n = 16, age 19–30 years), while in the group with 4–20 years of hospitalization (n = 30, age 24–45 years) the recorded OD values (0.85 ± 0.4 OD units) were practically indistinguishable from those of the control group. Conclusions: In the adult schizophrenic patients, the PAA blood test remains valid for patients who were hospitalized for less than 3 years. Drug treatment, length of disease and age can be assumed to reduce the PAA level considerably.

Blind Verification of Elevated Platelet Autoantibodies in Serum of Schizophrenic Patients – Part I: Young Subjects

Background: It has been hypothesized that the etiology of schizophrenia, in a distinct group of patients, originates from an autoimmune reaction against platelets. Previous open screenings have recorded significantly higher blood titers of platelet-associated autoantibodies (PAA) in schizophrenic patients as compared to normal healthy subjects. In addition, young schizophrenic patients at the early stages of their disorder displayed higher PAA titers than older patients with a longer duration of the disorder. A blood test based on these observations was proposed. Aim: To verify by a blind test a significant difference in PAA between young schizophrenic patients and matched healthy control subjects, for the validation of a blood test for schizophrenia. Methods: A total of 36 young schizophrenic patients in an active psychotic state, aged 13–20 years (mean ± SD: 16.2 ± 2.1 years) with an average PANSS score of 115.6 ± 14.5 and illness duration of 9.5 ± 9.4 months, were examined. The control group consisted of 49 healthy young subjects between the ages of 13 and 21 years (16.2 ± 2.2 years). The blood titers of PAA were evaluated blindly using an optimized ELISA test, expressed by a linear optical density (OD) scale. The blood samples of all participants were tested anonymously, and were scored under a code number. A test recording above 1.3 OD units was defined as positive. Results: The PAA titers of schizophrenia patients (1.6 ± 0.4 OD units, range: 0.7–2.3 OD units) were significantly higher than those of the control group (1.0 ± 0.4 OD units, range: 0.4–1.8 OD units; p < 0.0001). In 61% of the young schizophrenic patients (22 out of the 36 patients), a positive result (OD >1.3 units) was recorded. In the control group, only 12.2% (6 of the 49 subjects) displayed a positive result (p < 0.0001). Conclusions: These findings support further assessment of PAA titers as a potential biomarker for patients with clinical signs and symptoms of schizophrenia.

Endogenous retrovirus type W GAG and ENV antigenaemia in serum of schizophrenic patients

Recent and independent molecular studies have shown an association between Human Endogenous Retroviruses type ''W'' family (HERV-W) and Schizophrenia, mostly by PCR studies, but none has yet addressed specific antigen detection in living patients. HERV-W GAG (Matrix epitope) and ENV (Envelope epitope) proteins were dosed in the serum of patients with Schizophrenia and controls with a dedicated immunoassay set-up with specific monoclonal antibodies to either antigen. In schizophrenic patients, positive antigenaemia for ENV and for GAG was found in nearly 50% of cases. Difference with healthy controms was very significant (p < 0,01). All positive sera for ENV were also positive for GAG. Significant correlation was found between ''ENV'' antigenaemia, a protein causing dysimmune inflammatory effects and C-Reactive Protein levels-CRP, a systemic inflammation biomarker now known to be a hallmark of neurodegenerative forms of Schizophrenia. It is thus quite interesting to observe that, beyond association with systemic inflammation, HERV-W protein detection in blood here associates ENV and GAG antigen with coincident detection by three different monoclonal antibodies targeting distinct epitopes. This raises the question of coincident release of both proteins in the bloodstream or of HERV-W retroviral particles (such as ''Multiple Sclerosis Associated RetroViral'' particles, MSRV) as described by others in Schizophrenia as in Multiple Sclerosis. As viruses such as Influenza, long associated with risk for schizophrenia through perinatal infections have also revealed to activate HERV-W elements in human cells, we may now provide an hypothesis for a pathogenic cascade in association with HERV-W associating the following factors: environment factors long associated with early perinatal risk consisting in certain infectious agents, genetic factors represented by this retroviral endogenous family, the production of its pro-inflammatory ENV protein, and known ''inflammation-mediated'' neurotoxicity. Our present results thus confirm that HERV-W studies have opened a novel avenue of research in a neurodegenerative type of schizophrenia.

Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics

Accumulating evidence showed that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia. Decreased BDNF levels have been found in the serum of schizophrenic patients with mixed results. In the present study, we assessed serum BDNF levels in a large group of 364 schizophrenic patients (157 on clozapine, 89 on risperidone and 118 on typical antipsychotics), compared to 323 healthy control subjects matched for age and gender. The schizophrenia symptomatology was assessed by the Positive and Negative Syndrome Scale (PANSS), and serum BDNF levels were measured by sandwich ELISA. The results showed that BDNF levels were significantly lower in chronic patients with schizophrenia than in healthy control subjects (9.9 ± 2.0 ng/ml vs.11.9 ± 2.3 ng/ml, p < 0.0001). Lower BDNF levels were observed in patients treated with risperidone (9.3 ± 2.3 ng/ml) compared to those with clozapine (10.2 ± 2.0 ng/ml, p < 0.001) and typical antipsychotics (10.0 ± 2.1 ng/ml, p < 0.01). Furthermore, a stepwise multiple regression analysis identified types of antipsychotic drugs (beta = − 0.37, t = − 3.15, p = 0.001) and BDNF levels (beta = − 0.26, t = − 2.51, p = 0.014) as the influencing factor for the positive symptom subscore of PANSS. In addition, there was a sex difference in BDNF levels in patients with schizophrenia (9.7 ± 1.9 ng/ml for males vs.10.4 ± 2.1 ng/ml for female, p < 0.005), but not in normal controls. Our findings indicated decreased BDNF serum levels in chronic patients with schizophrenia, which may be related to clinical phenotypes, including gender, antipsychotic treatment and the severity of psychotic symptoms.

Therapeutic Drug Monitoring of Clozapine and Norclozapine in Human Serum Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

A rapid, sensitive, and specific method was developed and validated using ultra-performance liquid chromatography- tandem mass spectrometry (UPLC-MS-MS) for simultaneous determination of clozapine and its major metabolite norclozapine in human serum. The compounds were extracted from serum by a single step protein precipitation and analyzed using a UPLC-triple-quadrupole detection (TQD) system. Separation of compounds was achieved on a BEH C18 (50 mm x 2.1 mm, 1.7 microm) analytical column using methanol and water (both containing 0.2% ammonium hydroxide) as the mobile phase at a flow rate of 0.40 mL/min. The compounds were ionized in the electrospray ionization ion source of the TQD and were detected in the multiple reaction monitoring (MRM) mode. The MRM transitions m/z 327 --> 270 and m/z 313 --> 192 for clozapine and norclozapine, respectively, were used for the quantification ions. Clozapine transition 327 --> 192 and norclozapine transition 313 --> 270 were used as confirmation ions. Linear calibration curves in human serum were generated over the range of 10-2000 ng/mL for both clozapine and norclozapine with a correlation coefficient (r(2)) > 0.9970. Calibration curves exhibited consistent linearity and reproducibility. Interassay coefficients of variation (CV) (n = 20) were 3.04-4.94% for clozapine and 2.84-6.07% for norclozapine. Intra-assay CVs (n = 6, 20 days) were 0.61-1.26% and 1.62-2.21% for clozapine and norclozapine, respectively. The extraction recoveries were larger than 95% for both clozapine and norclozapine. The method was applied to the quantification of clozapine and norclozapine in the sera of schizophrenic patients, and the data revealed that the concentrations of two compounds varied significantly in the patients treated with clozapine.

S20-03 Determination of drug concentrations in serum and dopamine receptor occupancy in brain for optimal antipsychotic drug therapy

Evidence has been given that antipsychotic effects of dopamine receptor antagonists are associated with 60 and 80% striatal dopamine D2 and D3 receptor occupancy. Receptor occupancy correlates well with concentrations of the antipsychotic drugs in serum or plasma, much better than the dose. The latter is consistent with weak correlations between antipsychotic dose and serum concentrations and explained by the high interindividual variabilities in drug metabolism. Using positron emission tomography (PET) for in vivo determination of dopamine receptor occupancy in conjunction with drug concentration measurements “therapeutic windows” could be calculated for the atypical antipsychotic drugs amisulpride, risperidone and ziprasidone. On the other hand, analysis of drug concentrations in serum of schizophrenic patients who were treated with these drugs and who had responded to the medication confirmed the PET derived target levels and with some modifications also those of aripiprazole and clozapine. In vivo characterisation of dopamine receptor occupancy and measurement of blood levels should therefore be part of the clinical trials during the development of new antipsychotic drugs. They provide most relevant information for the later use of therapeutic drug monitoring to optimise the treatment of individual patients.

LIPIDOMIC PROFING OF PERIPHERAL BLOOD IN SCHIZOPHRENIA

Neurotrophic factors regulate neuronal development as well as synaptic plasticity, and their impairment is often implicated as a cause of schizophrenia. Among various neurotrophic molecules, brain-derived neurotrophic factor (BDNF) levels have been found to be increased in the corticolimbic regions of patients’ brains. In the present study, we assessed peripheral BDNF levels in whole blood as well as in the serum of two independent groups of schizophrenic patients (n=34 in each group) and healthy volunteers (n=35 and n=27, respectively). BDNF protein levels in fresh serum and blood of the patients and volunteers were measured using a two-site enzyme immunoassay and correlated with the number and decay of platelets. In addition to the studies of patients and volunteers, neuroleptic effects on BDNF levels were assessed by administering haloperidol to adult rats for 2 weeks or 5 months. The major findings were as follows: BDNF levels were significantly reduced in the serum of schizophrenic patients (P<0.005, Mann–Whitney U-test) but not in their whole blood. Antipsychotic dose did not correlate with serum BDNF levels. Moreover, chronic administration of haloperidol failed to decrease serum BDNF levels in adult rats. Abnormal levels of BDNF are evident not only in the brain of schizophrenic patients, but also in their peripheral blood. The BDNF reduction in serum but not in whole blood suggests a potential deficit in neurotrophic factor release in patients with schizophrenia.

Alteration in serum neural cell adhesion molecule in patients of schizophrenia

The neural cell adhesion molecule (N-CAM) plays important roles in neural migration, synaptogenesis and CNS development. Change of N-CAM fragments in CSF of schizophrenic patients was reported previously, and we aimed to detect difference in circulating N-CAM in the serum of schizophrenic patients and healthy controls. Samples were from 14 chronic schizophrenic patients including 3 drug naïve patients and 11 healthy controls. After removal of albumin and globulin, N-CAM fragments were measured by Western blot technique with monoclonal antibody. N-CAM immunoreactive bands were detected primarily at 180, 140, 120, 75, 68 and 52 kDa. Samples from patients and controls showed similar patterns of bands, but schizophrenic patients showed increases or decreases at some bands intensity compared to healthy controls. The 68 kDa/73-75 kDa bands intensity ratio was substantially elevated in schizophrenic patients (0.262+/-0.14 in patients, 0.065+/-0.04 in controls) especially, the three drug naïve patients had a higher value of this ratio compared to the medicated patients. One drug naïve patient showed a decrease in this ratio after one month of antipsychotic medication. The results suggest elevated membrane turnover and/or abnormalities in the regulation of proteolysis of N-CAM in schizophrenia.

Reduced serum BDNF levels in schizophrenic patients on clozapine or typical antipsychotics

Neurotrophic factors regulate neuronal development and synaptic plasticity, possibly playing a role in the pathophysiology of schizophrenia and other psychiatric disorders. Decreased brain-derived neurotrophic factor (BDNF) levels have been found in brains and in the serum of schizophrenic patients, but results are inconsistent. Also, clozapine may upregulate brain BDNF expression. In the present study, we assessed serum BDNF immunoreactivity in 44 schizophrenic patients (20 on clozapine and 24 on typical antipsychotics) and in 25 healthy volunteers. Serum BDNF levels were measured using an enzyme immunoassay. Healthy controls showed significantly higher levels of BDNF compared to the whole group of schizophrenic patients ( p < 0.001) as well as to the subgroups on typical antipsychotics and clozapine ( p < 0.001). Serum BDNF values for controls were 168.8 ± 26.3 pg/ml, for the clozapine group were 125.4 ± 44.5 pg/ml and for the group on typicals were 101.3 ± 51.6 pg/ml. BDNF values from patients on clozapine were non-significantly higher than values from patients on typical antipsychotics ( p = 0.09). Serum BDNF was strongly and positively correlated with clozapine dose ( r = 0.643; p = 0.002) but not with other demographic characteristics. These results reinforce previous findings of reduced serum BDNF levels in schizophrenic patients and suggest a differential effect of clozapine compared to typical antipsychotics on such levels.

Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients

Neurotrophic factors regulate neuronal development as well as synaptic plasticity, and their impairment is often implicated as a cause of schizophrenia. Among various neurotrophic molecules, brain-derived neurotrophic factor (BDNF) levels have been found to be increased in the corticolimbic regions of patients’ brains. In the present study, we assessed peripheral BDNF levels in whole blood as well as in the serum of two independent groups of schizophrenic patients ( n=34 in each group) and healthy volunteers ( n=35 and n=27, respectively). BDNF protein levels in fresh serum and blood of the patients and volunteers were measured using a two-site enzyme immunoassay and correlated with the number and decay of platelets. In addition to the studies of patients and volunteers, neuroleptic effects on BDNF levels were assessed by administering haloperidol to adult rats for 2 weeks or 5 months. The major findings were as follows: BDNF levels were significantly reduced in the serum of schizophrenic patients ( P<0.005, Mann–Whitney U-test) but not in their whole blood. Antipsychotic dose did not correlate with serum BDNF levels. Moreover, chronic administration of haloperidol failed to decrease serum BDNF levels in adult rats. Abnormal levels of BDNF are evident not only in the brain of schizophrenic patients, but also in their peripheral blood. The BDNF reduction in serum but not in whole blood suggests a potential deficit in neurotrophic factor release in patients with schizophrenia.

Glycoside in schizophrenic patients sera affects behavior of mouse forced swimming.

We found a glycoside in sera of schizophrenic patients. This glycoside increased climbing of mouse forced swimming and the climbing was decreased by dopamine D1 receptor antagonist SCH-23390 with a dose dependent manner. This glycoside had much reactivity of GalNAc alpha1-3GalNAc, but not that of polymannoses nor that of Gal beta1-3GlcNAc alpha1-serine or threonine. This strongly suggests that the glycoside is an isolated O-glycoside, but not N-glycoside nor O-glycoside having core 1 or 2. The present findings suggest that schizophrenic patients have the special glycoside affecting the D1 receptor activity in their serum.

Elevated cellular immune response to human heat-shock protein-60 in schizophrenic patients.

Heat shock protein-60 (HSP60) is implicated in several autoimmune diseases as a triggering antigen. Based on the autoimmune hypothesis of schizophrenia, we examined cellular and humoral responses against HSP60 and a series of its peptide fragments with peripheral blood samples of schizophrenic patients and healthy subjects each of group size between 12 to 32 participants. The average stimulation indices of peripheral blood mononuclear cells (PBMC) to HSP60 were 3.17 ± 0.36 (mean ± SE) for schizophrenic patients and 2.23 ± 0.24 (mean ± SE) for healthy subjects, with a significant difference between the groups (P = 0.0457). In parallel, 38 synthetic peptide fragments of HSP60, each of 18–21 amino acids, were tested for in vitro sensitization of PBMC. With one peptide (p32) the average stimulation index of PBMC from schizophrenic patients was significantly higher than that obtained for PBMC of control subjects (P = 0.0006). Comparing the cellular immune response to p32 between patients who were distinctive responders (n = 10) or non-responders (n = 10) to neuroleptic treatment indicated a similar elevation of cellular response in these groups. Antibodies against HSP60 were screened by dot-blot and ELISA in the sera of the above blood samples. Titers of IgG and IgM against HSP60 were found to be of similar magnitude in schizophrenic patients and in controls. Titers of IgA against HSP60 were somewhat higher in the sera of schizophrenic patients in comparison to sera of control subjects (P = 0.0605).