Platelet Monoamine Oxidase Activity Research Articles

Is low platelet MAO activity associated with antisocial behavior? evidence from representative samples of longitudinally observed birth cohorts

Lower platelet monoamine oxidase (MAO) activity has been associated with problem behaviors, including criminal behavior, but not all studies agree. We have examined platelet MAO activity and antisocial behavior involving police contact in a longitudinal birth cohort study. The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behavior and Health Study. Platelet MAO activity was measured at ages 15, 18 and 25 radioenzymatically with β-phenylethylamine as the substrate. Police contacts were self-reported in an interview and drug use in a questionnaire filled in during a laboratory visit. In cross-sectional analyses, males with the record of antisocial behavior had lower platelet MAO activity. In longitudinal mixed-effect regression models, this association was found to be independent of smoking. Furthermore, including smoking in the model revealed lower platelet MAO activity also in females with past antisocial behaviour. A further exploratory regression analysis with antisocial behavior at two levels of frequency and consideration of self-reported use of illicit drugs either in a single occasion or repeatedly demonstrated some “dose-dependency” in the relationship of antisocial behavior and platelet MAO activity. Platelet MAO activity was lower in male but not female subjects with basic education level as compared to secondary and higher education, but it was not related to non-verbal intelligence. Neither was platelet MAO activity associated with socio- economic status. In conclusion, antisocial behavior as occurring in general population is associated with low platelet MAO activity that probably reflects low capacity of the serotonergic system.

Association between platelet MAO activity and lifetime drug use in a longitudinal birth cohort study.

Platelet monoamine oxidase (MAO) activity, a marker of central serotonergic capacity, has been associated with a variety of problem behaviours. However, studies on platelet MAO activity and addictive drugs have not consistently linked MAO activity with addiction or reported to predict illicit substance use initiation or frequency. Platelet MAO activity and illicit drug use was examined in a longitudinal birth cohort study. The sample included both birth cohorts (original n = 1238) of the Estonian Children Personality Behaviour and Health Study. Longitudinal association from age 15 to 25years between platelet MAO activity and lifetime drug use was analysed by mixed-effects regression models. Differences at ages 15, 18 and 25 were analysed by t-test. Cox proportional hazard regression analysis was used to assess the association between platelet MAO activity and the age of drug use initiation. Male subjects who reported at least one drug use event had lower platelet MAO activity compared to nonusers, both in cross-sectional and longitudinal analyses. Males with low platelet MAO activity had started to use drugs at a younger age. Moreover, in male subjects who had experimented with illicit drugs only once in lifetime, low platelet MAO activity was also associated with higher risk at a younger age. In females, platelet MAO activity was not associated with drug use. In males, low platelet MAO activity is associated with drug abuse primarily owing to risk-taking at early age.

Platelet MAO activity and COMT Val158Met genotype interaction predicts visual working memory updating efficiency

The exact mechanism how serotonergic and dopaminergic systems relate to one another in working memory (WM) updating is unknown. Platelet monoamine oxidase (MAO) has been used as a marker for central serotonergic capacity, and catechol-O-methyltransferase (COMT) as a marker for central dopaminergic capacity. This study aimed to describe the interaction of platelet MAO activity and COMT Val158Met genotype in visual working memory updating: the ability to replace old information with new within hundreds of milliseconds. Previous studies suggest that platelet MAO activity and COMT Val158Met genotype could have an interaction effect on working memory. However, there are no studies that have directly examined the interaction of these biomarkers in WM updating. We used a 2-back updating task with facial expressions and defined updating efficiency as response times for correct responses. 455 subjects from a population representative sample were included. Mixed models were used for data analysis with an aim to study the interaction of COMT Val158Met genotype (Val/Val, Val/Met and Met/Met) and the level of MAO activity (high vs low). Education, IQ, sex, simple reaction times, and overall updating accuracy were included as covariates. We found that the effect of COMT Val158Met on updating efficiency depends on the level of platelet MAO activity. Low MAO in contrast to high MAO was associated with an increase in updating efficiency in Val/Met but a decrease in Met/Met. The results are discussed in the context of serotonin and dopamine functions in brain regions related to WM. The findings support the view that serotonin modulates dopaminergic activation in updating and contribute to understanding the role of serotonin in PFC, top-down inhibitory signals, and its interactions with dopamine in WM processes.

Increased Platelet Monoamine Oxidase Activity in Patients on Acute Stage of Ischemic Insult as A Potential Biomarker of a Better Functional Outcome of the Illness

Alteration of biogenic monoamines (serotonin and dopamine) metabolism is one of the pathogenetic mechanisms that affect processes of neuroplasticity during focal brain ischemia [1].

Relapse of drunk driving and association with traffic accidents, alcohol-related problems and biomarkers of impulsivity.

Individual biological predispositions should play a role in risky driving behaviour. Platelet monoamine oxidase (MAO) activity, dopamine transporter gene (DAT1) and neuropeptide S receptor 1 (NPSR1) gene polymorphisms have been identified as markers of impulsivity, alcohol use and excessive risk-taking. We aimed to find out how this knowledge on neurobiology of impulsivity applies to drunk driving and traffic behaviour in general. We have longitudinally examined the behaviour of drunk drivers (n = 203) and controls (n = 211) in traffic, in association with their alcohol-related problems, personality measures and the three biomarkers. We analysed differences between the subjects based on whether they had committed driving while impaired by alcohol (DWI) violation in a 10-year time period after recruitment or not and investigated further, what kind of predictive value do the different biomarkers have in committing DWI and other traffic violations and accidents. The original drunk drivers group had lower platelet MAO activity but further DWI was not significantly associated with this measure. Being a NPSR1 T-allele carrier contributed to the risk of repeatedly committing DWI. DAT1 9R carriers in contrast were involved in more traffic accidents by their own fault (active accidents), compared to 10R homozygotes in the whole sample. All groups with DWI also had significantly more alcohol-related problems and higher scores in maladaptive impulsivity compared to controls without DWI. Established biological markers of alcohol use and impulsivity can be reliably associated with everyday traffic behaviour and help in contributing to the understanding of the need for more personalized prevention activities.

Platelet monoamine oxidase activity and interpersonal violence in male suicide attempters

Low platelet monoamine oxidase B (MAO-B) activity, proxy of low central serotonergic functions, has been shown to correlate with criminal behavior in adolescents that come from an unfavorable psychosocial environment but not in adolescents from good conditions, indicating a link between environment, MAO-B activity and aggressive behavior. The purpose of this study was to examine the association between MAO-B activity and lifetime interpersonal violence in suicide attempters. The study included a total of 28 suicide attempters (18 men and 10 women). Assessments of childhood exposure to and expressed interpersonal violence during childhood and as an adult were carried out with the Karolinska Interpersonal Violence Scale (KIVS). Platelet MAO-B activity was measured with 2-phenylethylamine (b-PEA) as substrate. Broken down by gender, the correlations between platelet MAO-B activity and both exposure scores to interpersonal violence as a child and expressed lifetime interpersonal violence were significant in male suicide attempters (r = −0.61, p = 0.035; r = −0.84, p = 0.0005), but not in women. Our finding of significant associations between interpersonal violence and low MAO-B activity need to be replicated in other cohorts of suicide attempters.

The association of measures of the serotonin system, personality, alcohol use, and smoking with risk-taking traffic behavior in adolescents in a longitudinal study

Studies on the neurobiological basis of risk-taking behavior have most often focused on the serotonin system. The promoter region of the gene encoding the serotonin transporter contains a polymorphic site (5-HTTLPR) that is important for the transcriptional activity, and studies have demonstrated its association with brain activity and behavior. Another molecular mechanism that reflects the capacity of the central serotonin system is the activity of the enzyme monoamine oxidase (MAO) as measured in platelets. The purpose of the present study was to examine how measures of the serotonin system (platelet MAO activity and the 5-HTTLPR polymorphism), personality variables, alcohol use and smoking are associated with risk-taking traffic behavior in schoolchildren through late adolescence. The younger cohort of the longitudinal Estonian Children Personality Behaviour and Health Study (originally n = 583) filled in questionnaires about personality traits, smoking status, alcohol use and traffic behavior at age 15 and 18 years. From venous blood samples, platelet MAO activity was measured radioenzymatically and 5-HTTLPR was genotyped. During late adolescence, subjects with lower platelet MAO activity were more likely to belong to the high-risk traffic behavior group. Male 5-HTTLPRs′-allele carriers were more likely to belong to the high-risk traffic behavior group compared to the l′/l′ homozygotes. Other variables predicting risk group were alcohol use, smoking and Maladaptive impulsivity.The results suggest that lower capacity of the serotoninergic system is associated with more risky traffic behavior during late adolescence, but possibly by different mechanisms in boys and girls.

Smoking habits – Associations with personality/behavior, platelet monoamine oxidase activity and plasma thyroid hormone levels

The objective was to outline results from our scientific studies on the associations among childhood behavior, adult personality, and biochemical factors in smoking habits. The studies consisted of: (1) follow-up of young criminals and controls, subdivided into risk for antisocial behavior groups, based on childhood rating levels of a projective test; and adult smoking habit groups; and (2) a large group of young adults examined on the same inventories. Personality in terms of KSP and EPQ-I scale scores, controlled for intelligence, indicated that the high and very high risk groups displayed significantly higher self-rated impulsiveness, anxiety, and nonconformity, as compared to the low risk group. Further, the very high risk group subjects, found to be overrepresented among subjects with heavy smoking habits, displayed lower mean platelet MAO-B activity and higher thyroid hormone levels than the low risk group. Thus, the higher the childhood risk for antisocial behavior, the clearer the adult personality pattern making subjects more disposed for smoking appeared; and the higher smoking habits, the stronger the relationships with biochemical measures. Results are discussed in terms of possible underlying mechanisms influencing personality and smoking habits.

A Biomarker of Risk-Prone Behavioral Phenotype Correlates With Winning in a Game of Skill

Abstract. The predisposition to take risk is a personality trait associated with dangerous or maladaptive behavior. Related to this, biomarkers associated with risk proneness such as low platelet monoamine oxidase (MAO) activity level are typically considered as prognostic for higher likelihood of undesirable behavior in real-life settings. In this study we explored whether this biomarker is also indicative of risk proneness in a game situation where serious real-life adaptations and motivations are absent or minimized and risk is more or less symbolic. We adapted a game of skill where in order to get a high score “risky” actions had to be taken by the players. Scores obtained in the game correlated with the (relatively low) platelet MAO activity. Our results show that (1) the same markers that are informative for real-life behavior and adaptations involving risk and/or sensorimotor skills based performance may be informative also in a game setting, (2) in specific circumstances biomarkers associated with predisposition to risk may be associated with success, and (3) the novel game of skill tested in this context has a potential to be developed to a model of risk-involving behavior allowing quantifiable dependent measures of performance and purposeful manipulation of variables without real adverse effects on health or social relations.

A New Risk Factor for Traumatic Spinal Cord Injury.

Several behavioral factors such as violence, impulsivity, and alcohol-related problems are associated with traumatic spinal cord injury (TSCI). Such factors have been associated with inherently low neuronal serotonergic capacity that in turn is reflected in low activity of monoamine oxidase (MAO) as measured in platelets. The aim of the study was to characterize platelet MAO activity and impulsivity in persons with TSCI. Data were collected from 93 patients with TSCI and compared with 93 age- and gender-matched control subjects. Platelet MAO activity was measured radioenzymatically and expressed as nanomoles of beta-phenylethylamine oxidized per 10 to the tenth power platelets per minute. Facets of impulsivity were self-reported using Barratt Impulsiveness Scale (BIS-11). Most of the patients were men (87%). The mean time from TSCI was 4.3 ± 3.7 years. Twenty-one (24%) patients reported social problems associated with alcohol, and 30 (39%) patients had consumed alcohol before the trauma. Platelet MAO activity was significantly lower among the patients with TSCI (6.4 ± 3.2 vs.10.8 ± 5.2, p < 0.0001). This difference was not affected by consideration of their smoking status. The patients with TSCI had significantly higher BIS-11 impulsivity compared with the controls (62.8 ± 10.0 vs. 55.4 ± 8.6, p = 0.0001). The patients with TSCI have lower platelet MAO activity, and they are more impulsive compared with the healthy controls. Our results indicate that both low platelet MAO activity and high impulsivity are important risk factors for TSCI that can have predictive value and aid in undertaking preventive measures.

Potential neurobiological ADHD biomarkers

ObjectivesPathogenetic mechanisms of hyperkinetic syndrome (HKS) or attention deficit hyperactivity disorder (ADHD) are not clear.AimTo elucidate some aspects of monoamine involvement in pathogenesis of disorder and response of monoaminergic systems to psychostimulant medication.MethodsLevels of different monoamines, their metabolites and N-methylnicotinamide (end product of kynurenine pathway) were measured in daily samples of urine from children (7–11 years old) with mild and severe HKS using fluorimetric and chromatographic methods as well as platelet monoamine oxidase (MAO) activity. Thirty children with mild HKS received psychostimulant Sydnocarb 5–15 mg daily for 1–1.5 months (for ethical reasons children with severe HKS were not included in study).ResultsHKS was accompanied by activation of dopaminergic and inhibition of noradrenergic systems. There were found metabolic differences between two forms of HKS. Compared with mild HKS, severe HKS was characterized by significant 2-fold increase of MAO activity and L-dopa, dopamine and adrenaline excretion. After sydnocarb treatment children's clinical status improved along with decrease of excretion of homovanillic, vanillylmandelic and 5-hydroxyindoleacetic acids and increase of N-methylnicotinamide.ConclusionsResults indicate that dopaminergic and noradrenergic systems play important role in pathogenesis of HKS. Clinical improvement of HKS children was accompanied by significant increase of N-methylnicotinamide excretion. It is proposed that increased urine excretion of kynurenine metabolite–N-methylnicotinamide and N-methylnicotinamide/5-hydroxyindoleacetic acid ratio can serve as potential biomarkers for evaluation of efficacy of psychostimulant medication. We hypothesize that kynurenine system plays significant role in pathogenesis of HKS/ADHD.Disclosure of interestThe authors have not supplied their declaration of competing interest.

NEUROBIOLOGICAL BASES OF ALCOHOL ADDICTION.

Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter amines, i.e. serotonin, adrenaline, noradrenaline and dopamine. Thus, this enzyme is the key factor for maintaining cytoplasmic concentration of various neurotransmitters and for regulation of the neurotransmitting synaptic activity. Taken this MAO function into consideration, MAO is the enzyme included in the etiology and pathogenesis of various neuropsychiatric and neurological disorders. The finding of the decreased platelet MAO activity in various psychiatric disorders has brought us to the assumption that this enzyme may be a constitutional/genetic indicator (trait marker) or an indicator of disease condition (state marker) in biologic psychiatry. There are only a few studies of alcohol addiction researching the connections of the MAO coding gene polymorphism and alcoholism; however, these studies are primarily related to the variable number of tandem repeats (VTNR) polymorphism in the regulatory gene region for MAO-A, considered to influence the transcription activity/functionality of the enzyme.

Biochemical Bases of Monoamine and Hormonal Interactions in Pathogenesis of Anxious Depression: a Hypothesis.

Biochemical bases of interaction between monoaminergic systems and cortisol as one of the main component of hypothalamic-pituitary-adrenal axis in pathogenesis of anxious depression are investigated poorly. Elucidate some biochemical aspects of interaction of monoaminergic systems and cortisol in pathogenetic mechanisms of anxious depression. Patient's state (61 patients) according to ICD-10 criteria was defined as a depressive episode as an independent disease (F32.1) and in the structure of recurrent depressive disorder (F33.1). The anxiety in the structure of the depression was the main indication to inclusion in the investigation. According to Hamilton rating scale for depression and Hamilton rating scale for anxiety the total points were 21.83 and 18.00, respectively, that corresponded to severe depressive disorder and severe anxiety. 43 of 61 patients were investigated biochemically. There were revealed significant increase of platelet monoamine oxidase activity and cortisol level. It means that patients with anxious depression are characterized by profound disturbances of monoamine metabolism and hormonal status that are the reflection of disturbed homeostasis as a whole. There are revealed tight interaction between monoamines and cortisol. We hypothesize about biochemical mechanisms of disturbed balance between serotonergic and noradrenergic systems and cortisol in anxious depression.

Relationships between Platelet MAO-B Activity and Personality Styles in Acute and Weight-Recovered Young Patients with Anorexia Nervosa

Previous studies have shown relationships between personality styles and markers of serotonergic functioning, but data on patients with anorexia nervosa (AN) are scarce. The personality styles and disorder inventory was administered to 47 acute patients with anorexia nervosa (acAN), 27 weight-recovered patients (recAN) and 72 healthy controls (HC) aged between 14 and 21 years. Platelet monoamine oxidase (MAO-B) activity was assayed with [14C]-β-phenylethylamine as substrate. AcAN had significant elevated scores on 9 of the 14 personality style subscales when compared to HC, whereas recAN were largely normal. Platelet MAO-B activity and "ambitious/narcissistic" scores correlated negatively in acAN. In recAN we found positive correlations between MAO-B and personality subscores. The inverse relationship between a cluster B personality style and MAO-B activity in acAN is in accordance with studies in other patient populations. In contrast, positive associations between problematic personality styles and MAO-B activity in recAN combined with the overall decreased MAO-B activity in this group adds to the existing evidence suggesting a general dysfunction of the serotonergic system as a trait marker for AN.

Change in platelet monoamine oxidase activity in the acutest period of ischemic stroke is associated with the degree of neurological recovery

We studied monoamine oxidase activity (MAO) in platelets of patients in the acute period of ischemic stroke. Neurological deficit was evaluated by the data of clinical examinations and scales. In 80% patients MAO activity was considerably increased on 3-5 day after stroke. We found a correlation between increased MAO activity on 3-5 day after ischemic stroke and regression of neurological deficit on day 21 after ischemic stroke. The increase in MAO activity during the acute period of ischemic stroke is presumably a compensatory response aimed at stabilization of tissue homeostasis.

Psychobiology of borderline personality traits related to subtypes of eating disorders: A study of platelet MAO activity

Increased and decreased levers of platelet monoamine oxidase (MAO) activity have been reported in patients with eating disorders, indicating abnormalities of the serotonin turnover. However, whether these findings are related to eating disorders or are rather reflecting the pathophysiology of borderline personality traits in these patients is still unknown. Platelet MAO activity and comorbid personality disorders were investigated in 72 patients with different subtypes of eating disorders (ED) and in a group of 28 healthy controls. ED patients comprised the following subtypes: 25 anorexia nervosa (AN) restrictive, 14 AN binge eating–purging (AN b-p), 3 anorexia nervosa not otherwise specified (AN NOS) and 30 bulimia nervosa (BN). Personality disorders and traits were assessed with the Structured Interview for Personality Disorders (SCID-II), the Zanarini Rating Scale for Borderline Personality Disorder, and the Barrat Impulsiveness Scale. Platelet MAO activity was significantly lower in ED patients with comorbid borderline personality disorder (BPD) than in ED without Borderline personality disorder (BDP). Platelet MAO activity was significantly and inversely correlated with the number and severity of BPD clinical features. In the subsample of patients with binge eating–purging symptoms (AN b-p, AN NOS and BN), platelet MAO activity was significantly lower in binge–purge patients with comorbid BPD than in binge–purge patients without BPD. The whole group of eating disorders had a significantly reduced lever of platelet MAO activity compared with the control group. The results suggest that low platelet MAO activity might characterize eating disorders with comorbid borderline personality traits, reflecting greater serotonin dysfunction in these patients. The role of decreased platelet MAO as an endophenotype with specific clinical manifestations should be explored in future studies.

Activation of monoamine oxidase as a compensatory response during ischemic insult

We measured the activity of monoamine oxidase (MAO) in platelets taken from 25 patients in the acute period of ischemic hemispheric insult. The neurological deficit of the patients on arrival and discharge from the hospital was evaluated using the data from clinical examinations and tests. In 64% of the patients with ischemic insult, we found a considerable increase in the activity of platelet MAO on the 3rd–5th day of the insult, as compared to the control group (P < 0.001). We found a correlation between the increase in MAO activity on the 3rd–5th day after ischemic insult and a decrease in neurological deficit on the 21st day after the insult. The increase in the MAO activity during the acute period of ischemic insult is, presumably, one of compensatory responses that develop during insult.

FC13-09 - Antidepressant tianeptine (TIA) action is based on the acceleration of serotonin turnover in the synapse: a hypothesis

IntroductionNeurochemical mechanism of TIA action is not clear.AimTo develop possible mechanism of TIA action in patients with anxious depression (Uzbekov et al., 2006, 2009).ResultsIt was found twofold increase of platelet monoamine oxidase (MAO) activity in depressed patients and its significant decrease under TIA action.DiscussionSynapse is considered as a complex biological system (nerve ending + astrocytes). It is supposed that at normal conditions about 75% of serotonin released in synaptic cleft undergoes functional inactivation by its reuptake in presynaptic ending. The remaining serotonin is taken up by astroglia and is undergone its irreversible (chemical) inactivation under MAO action.According to our hypothesis TIA enhancing serotonin reuptake decreases serotonin level in synaptic cleft. Simultaneously in patients-responders we have established the decrease (inhibition) of MAO activity that promotes increase of serotonin concentration in synaptic cleft. It has been shown that TIA activates serotonin release from presynaptic ending (Labrid et al., 1992). Thus TIA enhances not only serotonin reuptake but simultaneously activates its surge from the ending into synaptic cleft. We conclude that under TIA action serotonin turnover rate in the synapse is increased that promotes increase in the unit of time serotonin concentration on postsynaptic receptors; this process is accompanied by decrease of MAO activity.ConclusionThe first time in the literature we propose the hypothesis about neurochemical mechanism of TIA action. Proposed mechanism mainly refers to the first acute phase of TIA action directed on the normalization of serotonergic neurotransmission.

S45-03 - Biochemical and biophysical aspects of the pathophysiology of first episode of schizophrenia

IntroductionThe knowledge of pathophysiology of first psychotic episode is still fragmentary.AimTo investigate some biochemical and biophysical parameters in first-episode, drug-naive schizophrenic (FES) patients.Methods26 FES patients (ICD-10; F 20.0 and F 20.3) and 15 age-and gender-match volunteers were investigated. Clinical severity of FES patients were assessed by PANSS scale. Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, middle-mass endotoxic molecules (MMEM) and malondialdehyde (MDA) levels were measured using respective methods. Steady-state and subnanosecond fluorescent spectroscopy were used for the investigation of albumin conformational changesResults Severity of disorder prior the treatment was 75.5 ± 2.2 (PANSS score). FES patients were characterized by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of albumin conformational and functional parameters (“effective” albumin concentration and“reserve” of albumin binding) estimated by steady-state fluorescent spectroscopy were insignificant. Factor analysis revealed that MAO and SSAO are more tightly connected with pathogenetic mechanisms of FES then MMEM, MDA and albumin functional parameters. Significant conformational changes of albumin of FES patients were detected using pulse fluorescent spectroscopy with subnanosecond resolution. Results are compared with the data received in chronic schizophrenic patients.ConclusionFrom pathophysiological point of view FES is the initial step in development of pathologically disturbed biochemical status characteristic to chronic schizophrenia.The study was supported by grant # 3156 from International Science and Technology Center (ISTC).

P03-348 - Biochemical and biophysical aspects of the pathophysiology of first episode of schizophrenia

IntroductionThe knowledge of pathophysiology of first psychotic episode is still fragmentary.AimTo investigate some biochemical and biophysical parameters in first-episode, drug-naive schizophrenic (FES) patients.Methods26 FES patients (ICD-10; F 20.0 and F 20.3) and 15 age-and gender-match volunteers were investigated. Clinical severity of FES patients were assessed by PANSS scale. Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, middle-mass endotoxic molecules (MMEM) and malondialdehyde (MDA) levels were measured using respective methods. Steady-state and subnanosecond fluorescent spectroscopy were used for the investigation of albumin conformational changes.ResultsSeverity of disorder prior the treatment was 75.5 ± 2.2 (PANSS score). FES patients were characterized by significant increase in MAO activity (99%) and MMEM concentration (124%) and significant decrease in SSAO activity (26%) as compared with controls. Changes of albumin conformational and functional parameters (“effective” albumin concentration and “reserve” of albumin binding) estimated by steady-state fluorescent spectroscopy were insignificant. Factor analysis revealed that MAO and SSAO are more tightly connected with pathogenetic mechanisms of FES then MMEM, MDA and albumin functional parameters. Significant conformational changes of albumin of FES patients were detected using pulse fluorescent spectroscopy with subnanosecond resolution. Results are compared with the data received in chronic schizophrenic patients.ConclusionFrom pathophysiological point of view FES is the initial step in development of pathologically disturbed biochemical status characteristic to chronic schizophrenia. The study was supported by grant # 3156 from International Science and Technology Center (ISTC).