Links of platelet glutamate and glutathione metabolism with attenuated positive and negative symptoms in depressed patients at clinical high risk for psychosis.

Aim of the study is to reveal clinical and biological correlations in patients with adolescent depression and attenuated psychotic symptoms. Activity of platelet enzymes involved in glutamate-, glutathione- and energy metabolism was evaluated in control group and in the patients, because these systems are suspected as related to pathogenesis of psychosis. Adolescents (78 men, 16-25 years old) hospitalized with the first acute depressive state composed two groups: with prevalence of attenuated psychotic positive or negative symptoms (Gr1 and Gr2, 48 and 30 patients, respectively). Control group comprised 20 mentally healthy men of 19-25 years old. Gr1 differed significantly from Gr2 in scores by the Scale of Prodromal Symptoms (SOPS) for positive symptoms, p < 0.001, for disorganization symptoms, p < 0.003, and for total SOPS score, p < 0.001, before the treatment started. When patients from either Gr1 or Gr2 were compared with the control group, significantly decreased baseline activities of platelet glutamate dehydrogenase (GDH), glutathione reductase (GR) and glutathione S-transferase (GST) were found (p < 0.0001). Different correlations were found between baseline enzymatic activities in Gr1 and Gr2: GDH activity correlated with GR activity in Gr1 (R = 0.37), and with GST activity in Gr2 (R = 0.70). Significant correlations were found only in Gr2 between the delta of scores by SOPS negative symptoms (SOPS-N) under treatment and baseline GDH, GST, and GR activities (R = - 0.36, R = - 0.60, and R = 0.38, respectively). The found correlations of the baseline enzymatic activity levels with the value of the decrease (delta) in SOPS-N scores under the treatment represent interest for the prediction of the pharmacotherapy efficiency.

Activity of energy, glutamate, and glutathione metabolism enzymes in blood cells of elderly patients with depression

Heterogeneity of depression in older adults is a challenge for the development of person-centered treatment. To address this, we studied glutamate and glutathione metabolism enzymes in blood cells in 53 older adult patients with depression and 20 controls. Patients with depression had decreased platelet glutathione-S-transferase and erythrocyte glutathione reductase. The biochemical and clinical data contributed to three clinical clusters that are not linked to the onset of depression or its duration but were related to anxiety, cerebrovascular and cardiovascular comorbidities, including parkinsonian features such as tremor, akathisia, and rigidity. These findings could aid person-centered diagnosis and outcomes and timely successful treatment(s) of depression in older adults. (AU)

Recognition of Emotional and Neutral Visual Scenes in Carriers of the MAOA, COMT, DRD4, and 5HT2A Gene Polymorphisms.

Background: It is known that some genes regulate neurochemical metabolism, and their polymorphisms affect cognitive performance, including the ability to categorize emotionally significant information. Objective: The aim of our study was to analyze the recognition of emotional and neutral visual scenes in carriers of different polymorphic variants of the MAOA, COMT, DRD4, and 5HT2A genes. Design: The study sample consisted of 87 university students (Caucasians, women 63%, average age 20.4±2.6 years). The genotypes of the COMT, 5HT2A, and DRD4 genes were determined by polymerase chain reaction. Agarose gel electrophoresis was used to determine the number of tandem repeats of the MAOA gene. Three hundred sixty (360) photographic images of scenes of different emotional valence (positive, negative, and neutral - 120 images for each category) were used as stimuli. These images were classified by expert assessments. The images were presented in a random sequence. The exposure time was 700 ms. The research participants were asked to determine the emotional valence of each scene. Results: We found that only the COMT gene genotype affected the recognition of emotional and neutral visual scenes. Carriers of the COMT Val/Val genotype, which causes dopamine to stay in the synaptic space for a shorter time, are better in recognizing and demonstrate higher sensitivity to the emotional content of scenes. Carriers of the Val/Met genotype demonstrated the worst ability to differentiate the emotional valence of visual scenes. Conclusion: This study has shown that the length of stay of monoamines in the synaptic space regulated by the COMT gene affects the recognition of emotional visual information.

Emotional Intelligence in Carriers of Different СОМТ, BDNF, DRD2 and HTR2A Genotypes.

Background: Emotional intelligence is the ability to quickly and correctly recognize the emotional expressions of other people and to express and manage one's own emotions. It contributes to the success of a person in activities related to communication and interaction with people. Emotional intelligence has been studied largely in the context of organizational and education psychology, but less is known about the influence of genetics on it. Objective: We aim to study emotional intelligence in carriers of different СОМТ, BDNF, DRD2, and HTR2A genotypes. Design: We used three methods to measure emotional intelligence. Mayer-Salovey-Caruso Emotional Intelligence Test is a set of tasks with forced choice and frequency-based correct responses. We also applied two self-report questionnaires by Lyusin and Hall. We recruited 280 participants who took part in all three measures. We also identified their genotypes of the СОМТ, BDNF, DRD2, and HTR2A genes. Results: Carriers of the Val/Met genotype of the COMT gene, A/A genotype of the HTR2A gene and C/C genotype of the DRD2 gene showed the highest level of emotional intelligence, while no differences were found between carriers of the BDNF genotypes. These data were obtained by using the Mayer-Salovey-Caruso Emotional Intelligence Test. Self-report scores of emotional intelligence did not differ between carriers of different genotypes across all four of the genes in question. Conclusion: Mayer-Salovey-Caruso Emotional Intelligence Test scores were differed for carriers of some genotypes, whereas self-reported emotional intelligence scores did not differ between according to genotype.

Association between categorization of emotionally-charged and neutral visual scenes and parameters of event-related potentials in carriers of different COMT, HTR2A, BDNF gene genotypes.

Background: This study aimed to discover the association between parameters of event-related potentials (ERPs) and categorization of images of visual scenes, both emotionally-charged and neutral, in carriers of different genotypes of the COMT, HTR2A, BDNF genes. Methods: Electroencephalogram (EEG) and ERPs were recorded at 128 leads, with two ear referents. Images of different visual scenes were presented to the study participants sequentially on a monitor screen. The participants' task was to examine these images and indicate what emotions (negative, neutral or positive) they elicit. Comparison of event-related potentials was carried out using unpaired Student t-test in EEGLAB toolbox. Results: COMT. A stronger reaction, as reflected in the amplitude of the ERPs, in participants with the recessive homozygous Met/Met genotype was observed on latency around 200 ms to the stimuli, assessed as positive. Carriers of dominant homozygous Val/Val genotype had higher amplitude of 200 ms peak when assessed scene images as either neutral or negative in comparison to other genotypes. Participant with the Val/Met heterozygous genotype had higher amplitude of ERP that Met/Met group on same latency when assessed stimuli as negative. HTR2A . Significant increase in negativity in the parietal-occipital regions revealed in the range of 350-420 ms in participants with the recessive homozygous A/A genotype when choosing any type of assessment, compared to carriers of the heterozygous genotype A/G and the dominant homozygous G/G genotype. BDNF. Participants with Val/Val genotype categorized the visual images more thoroughly, as reflected in greater activation of the parietal-occipital zones and higher amplitude on ERP peak on 190 ms (negative assessment) and 160 ms (neutral assessment) then Val/Met carriers. Conclusions: The COMT, HTR2A, BDNF gene different genotypes are associated with the process of categorizing emotionally charged and neutral visual scenes, and this relationship is reflected in the ERP parameters.

Platelet glutamate dehydrogenase activity and efficacy of antipsychotic therapy in patients with schizophrenia.

BACKGROUND: Evaluation of possible relationship between platelet glutamate dehydrogenase (GDH) activity and mental state of schizophrenia patients after antipsychotic pharmacotherapy. METHODS: Patients (n = 50) with chronic paranoid schizophrenia (F20.0) initially in acute psychotic state were examined before and after a treatment course with antipsychotics. When assessing the patients' states using PANSS, the "responder" category was attributed to those patients who had not less than 30% reduction in the score for the corresponding PANSS "subscale". The control group (n = 48) was ageand gender-matched with the patient group. Platelet glutamate dehydrogenase (GDH) activity was measured in patients twice, before and after the treatment course, and once in controls. RESULTS: Significantly reduced GDH activity was found in patients compared with controls. The patient group was divided into two subgroups according to median GDH activity at baseline: above and below the median GDH, subgroup 1 and subgroup 2, respectively. GDH activity significantly increased from its level at baseline after antipsychotic treatment in subgroup 2. Distribution of non responders / responders to antipsychotic treatment (by PANSS scores) was significantly uneven among subgroups 1 and 2. In subgroup 1, GDH activity levels significantly correlated with PANSS scores after the treatment course. CONCLUSIONS: Baseline platelet GDH activity might serve as a predictor of antipsychotic therapy efficacy in schizophrenia patients.

Empathy, but not mimicry restriction, influences the recognition of change in emotional facial expressions.

The current study addressed the hypothesis that empathy and the restriction of facial muscles of observers can influence recognition of emotional facial expressions. A sample of 74 participants recognized the subjective onset of emotional facial expressions (anger, disgust, fear, happiness, sadness, surprise, and neutral) in a series of morphed face photographs showing a gradual change (frame by frame) from one expression to another. The high-empathy (as measured by the Empathy Quotient) participants recognized emotional facial expressions at earlier photographs from the series than did low-empathy ones, but there was no difference in the exploration time. Restriction of facial muscles of observers (with plasters and a stick in mouth) did not influence the responses. We discuss these findings in the context of the embodied simulation theory and previous data on empathy.

Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia.

Basing primarily on the facts of altered levels of glutamate neurotransmitter, its receptors and transporters in schizophrenic brain, the "glutamatergic hypothesis" of schizophrenia has been broadened into the field of brain glutamate metabolism. Significantly changed levels of glutamine synthetase (GS) and glutamate dehydrogenase (GDH), the key enzymes involved in glutamine-glutamate cycling between neurons and glia, have been found in the prefrontal cortex (area 10) of patients with schizophrenia compared to controls (P<.01). The data were obtained by enzymatic activity determinations as well as immunoreactivity level evaluations for GS, glutamine synthetase-like protein (GSLP), and three GDH isoenzymes in brain extracts by immunoblotting using specific polyclonal and monoclonal antibodies. Inverse changes in amounts of proteins of GS and GSLP, as well as elevation in amounts of GDH isoenzymes have been observed in schizophrenia. The presented results provide evidence for the impairment of glutamate metabolism and, in turn, abnormalities in functioning of the glutamate-glutamine cycle in the frontal cortex of patients with schizophrenia.

Diversity of glutamate dehydrogenase in human brain.

Three forms of glutamate dehydrogenase (GDH, EC 1.4.1.3) are purified from human brain tissue. Two of them, named GDH I (consisting of 58+/-1-kDa subunit) and GDH II (consisting of 56+/-1 -kDa subunit), are readily solubilized and the third one, GDH III (consisting of 56+/-1-kDa subunit), is a membrane-associated (particulate bound) isoform. Kinetic constants were determined for GDH III. These GDH forms were found to differ in hydrophobicity as indicated by different affinity to Phenyl-Sepharose. All three GDH forms showed microheterogeneity on two-dimensional (2-D) gel electrophoresis. Specific polyclonal antibodies, which enable to determine the levels of immunoreactivities of all the GDH forms in human brain extracts by enzyme-chemiluminescent amplified (ECL)-Western immunoblotting, were obtained.