Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.

We investigated the associations of rs4680 COMT, rs6280 DRD3, and rs7322347 5HT2A with youth-onset schizophrenia in the Russian population in a case–control study, and the role of the genotype in the severity of clinical features. The association between rs7322347 and schizophrenia (p = 0.0001) is described for the first time. Furthermore, we found a link with rs6280 and rs4680 in females (p = 0.001 and p = 0.02 respectively) and with rs7322347 in males (p = 0.002). Clinical symptoms were assessed on three scales: the Clinician-Rated Dimensions of Psychosis Symptom Severity scale, Positive and Negative Syndrome Scale, and Frontal Assessment Battery. Gender differences in clinical features are of particular interest. In our study we found gender differences in the severity of clinical features—higher scores for delusions (Positive and Negative Syndrome Scale and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition) in males and higher scores for depression, delusions, somatic concern, motor retardation, poor attention were found in females.

Aim Schizophrenia manifests differently in women and men. This disease starts at a young age, leads to disability at working age. The aim of our work was to study sex differences, association between social factors and different parameters of the clinical picture and the course of the disease. Methods This study was performed using population of Russian patients (men: 345, women: 310). Patients were examined using DSM‐V, Bush‐Francis catatonia rating scale (BFCRS), Positive and Negative Syndrome Scale (PANSS), 4‐Items Negative Symptoms Assessment (NSA‐4) and Frontal Assessment Battery (FAB). Results Sex differences were mainly shown through negative symptoms, which were more severe in male patients. Men were shown to experience a decrease in social functioning and earlier age of onset. A positive family history further influenced negative symptoms and age of onset. When comparing scores before and after inpatient treatment (4 weeks), sex differences were not so pronounced. Female patients and patients with high levels of education, no conflictual relationship with family and active labour activity showed a later age of onset of the prodromal events and manifestation age. The decrease in the number of social contacts correlated with lower age of disability. The association between social factors and the severity of psychotic symptoms was shown across DSM‐V, PANSS, NSA‐4 and FAB, but not for BFCRS. Social factors were associated with negative symptoms of schizophrenia, but not with positive. Conclusion For successful treatment of patients with schizophrenia, the discussed factors must be considered and schizophrenia treatment methods should be primarily aimed at improving social functioning.

We investigated the associations of DRD3 rs6280, HTR1A rs6295, BDNF rs6265, SCL6A4 rs16965628, and 5HT2A rs7322347 with schizophrenia in a case–control study, and associations of these genetic variants with several clinical features. We also investigated markers of inflammatory response (C-reactive protein, IL-2, IL-6, IL-10), the activity of leukocytic elastase (LE) and α1-proteinase inhibitor (a1-PI), antibodies to S100B and myelin basic protein (MBP) in schizophrenia. Clinical symptoms were assessed on three scales: Positive and Negative Syndrome Scale, The Bush – Francis Catatonia Rating Scale and Frontal Assessment Battery. All SNPs were typed using predesigned TaqMan SNP genotyping assays. The biomarkers related to the immune system were routinely tested using ELISA kits. The association with schizophrenia was found for DRD3 rs6280 (p = 0.05) and HTR2A rs7322347 (p = 0.0013). We found differences between groups by parameters of LE and a1-PI and LE/a1-PI (p &lt; 0.001). And IL-6 was evaluated in the schizophrenia group (p &lt; 0.001). We showed that patients with the TT allele (BDNF rs6265) had more severe impairments in frontal lobe function. a1-PI can serve as a marker for assessing the severity of frontal lobe damage in patients with frontal dementia. We found some biological parameters reflecting the severity of frontal dysfunction in schizophrenia.

Objectives:The PANSS is utilized in clinical trials for assessment of psychopathology. In order to determine the status of a patient, comparisons within a general population are necessary. If several groups of patients are to be compared, gender, age, co-morbid diagnoses, and other factors affecting clinical status are not identically distributed.Aims:1) Phase 1: To establish the initial psychometric properties of the PANSS-Ru. 2) Phase 2: To establish normed-reference data for the PANSS-Ru.Methods:Phase 1: 40 patients with schizophrenia and other psychotic disorders. Phase 2: 375 individuals (n = 250 patients; n = 125 controls). Responses were assessed for internal consistency, stability, reliability, discriminative validity, and construct validity. Fifth percentile norms are presented as step functions. Data were compared to US norms.Results:40 subjects enrolled for Phase 1. Alpha coefficient of 0.88 verified good internal consistency. Test-retest comparisons verified time stability (r = 0.67 to 0.92). Correlation between subscale and the total scores ranged from 0.76 to 0.86, compared to > 0.83 for US norm studies. Internal consistencies were α > 0.745. Mean subscale/ total score were equivalent to US population norms within 13%. However, there was a difference of > 5 norm-based points for mean general psychopathology subscale. Norms had a sensitivity of 85% and specificity of 89%.Conclusions:Preliminary results show that different dimensions of symptom presentations in the Russian population may help to improve symptom-specific treatments, and will also provide comparison data for a Russian population. Further normative studies are warranted in other populations.