Effective treatment of FES patients may lead to achievement of long-term remission, decrease the number of relapses and increase the level of social activity and quality of life.

To study some pathophysiological mechanisms of FES.

The group of patients who were investigated clinically and biochemically consists of 26 persons (11 women and 15 men, average age 28.2 ± 9.5 years) with the first psychotic episode (F20.0; F20.3). Some biochemical parameters, representing the monoaminergic systems, and some biophysical parameters, representing reducing-oxidizing processes, were investigated. These parameters in all patients were estimated following the admission and prior to any treatment.

The severity of the disorder on admission to the clinic according to PANSS score was 75,5 ± 2,2 (i.e., moderately severe). Patients with FES were characterized by a significant increase of platelet momnoamine oxidase activity (by 107%; р < 0,01) and decrease of serum semicarbazide-sensitive amine oxidase activity (by 29%; p < 0,001) in comparison to the controls. Both reactive capability of SH-group (Cys-34 residue) of serum albumin, the main source of thiols of plasma and intersticial fluid, measured in reaction with thiol-specific reagent - dithyonitrobenzoic acide, and kinetic coefficient were decreased in FES patients (by 24%; p = 0,02) in comparison to controls.

These results show that FES patients are characterized by pronounced metabolic disturbances.

Investigate some properties of albumin binding sites in schizophrenic patients.

Properties of serum albumin binding sites were studied using quenching of fluorescence of probe K-35 (N-carboxyphenylimide of dimethylaminonaphthalic acid) with nitrate anion. Serum samples were collected from 24 schizophrenic patients and 24 healthy volunteers.

In the absence of quencher specific probe fluorescence in patients was 1,4 times higher than in controls. Fluorescent quenching constant for probe bound to albumin was 2,5 L/mol in patients versus 4,6 L/mol in volunteers (p< 0,01). Fluorescent fraction assessable to quenching was significantly lower in patients than in volunteers. Fluorescent decay studies on S-60 synchrotron have revealed in patient's albumin the redistribution between long-lived and short-lived molecules of the probe with increase of the latter. There were found decrease of albumin accessible SH-groups in schizophrenic patients as compared with volunteers.

In schizophrenic patients conformational state of albumin binding sites is significantly disturbed that can lead to changes in protein-ligand interaction and to damage of main albumin functions (transport and detoxification) and aggravation of endotoxicosis.

Neurochemical mechanism of TIA action is not clear.

To develop possible mechanism of TIA action in patients with anxious depression (Uzbekov et al., 2006, 2009).

It was found twofold increase of platelet monoamine oxidase (MAO) activity in depressed patients and its significant decrease under TIA action.

Synapse 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.

The 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.

The aim of the study was to investigate the state of parameters characterizing different sites of metabolism and the degree of endogenous intoxication in drug-naïve first episode schizophrenic patients (FES).

Platelet monoamine oxidase (MAO) and serum semicarbazide-sensitive amine oxidase (SSAO) activities, serum concentrations of middle-mass endotoxic molecules (MMEM) and malondialdehyde and parameters of serum albumin functional state (Uzbekov et al., 2006) were measured in 16 FES patients and 15 age-matched healthy volunteers.

Severity of disorder prior the treatment was 73.1±12.5 according to PANSS score. FES patients were characterized by significant increase in MAO activity (by 107 %) and MMEM concentration (by 140 %) and significant decrease in SSAO activity (by 29 %) as compared with controls. Degree of endogenous intoxication in 13 patients was assessed as moderate and severe. Changes of all other parameters were insignificant. Regression analysis has shown significant relationship of 3 parameters - MAO (p< 0,01), SSAO (p< 0,01) and MMEM (p< 0,02) with values of PANNS score. Three methods of extraction of factor analysis have revealed that MAO and SSAO are belonged to factor 1 whereas MMEM and albumin functional parameters - to factor 2.

It is supposed that MAO and SSAO are integral components of schizophrenia pathogenetic mechanisms. Comparing our earlier data on chronic schizophrenic patients with these data we suppose that FES patients are on the stage of the formation of the pathological state of metabolism.Study was partially supported by the ISTC grant 3156.

The aim of the study was to evaluate the response of different monoaminergic systems to psychostimulant treatment in children with mild form of hyperkinetic syndrome (HKS).

The levels of N-methylnicotinamide (end product of kynurenine pathway of tryptophan metabolism), 5-hydroxyindoleacetic (product of serotonin pathway of tryptophan metabolism), homovanillic and vanillylmandelic acids were measured in daily (3 days) urine samples of children (30 patients, 7-11 years old) with mild HKS with normal intellect or borderline mental insufficience. Biochemical measurements were performed before and 3 weeks after sydnocarb medication (5-15 mg sydnocarb daily). (Sydnocarb is a psychostimulant introduced into the clinical practice in the Soviet Union in the 70th of XX century).

After 3 weeks of sydnocarb therapy there were found the improvement of children's clinical status in both groups. It was followed by a significant decrease in the excretion of homovanillic (by 45 %), vanillylmandelic (by 35 %) and 5-hydroxyindoleacetic (by 50 %) acids but by a significant increase in N-methylnicotinamide excretion (by 30%).

Psychostimulant medication has revealed the involvement of kynurenine and serotonin in HKS pathogenetic mechanisms. There were found a reciprocal relationship between serotonergic and kynurenine systems. It is proposed the kynurenine hypothesis of pathogenesis of HKS. It is characterized by the decreased activity of kynurenine system in HKS children. Clinical improvement of HKS children under psychostimulant medication is connected with activation of kynurenine system along with the decrease of serotonergic activity.

The knowledge of pathophysiology of first psychotic episode is still fragmentary.

To investigate some biochemical and biophysical parameters in first-episode, drug-naive schizophrenic (FES) patients.

26 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.

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.

From 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).

The knowledge of pathophysiology of first psychotic episode is still fragmentary.

To investigate some biochemical and biophysical parameters in first-episode, drug-naive schizophrenic (FES) patients.

26 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

Results 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.

From 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).

Conformational changes of human serum albumin (HSA) can disturb its main functions.

To reveal serum albumin disturbances using the high-tech approaches in first episode schizophrenia.

First-episode drug-naïve schizophrenic (FES) patients were investigated. There were employed laser time resolved subnanosecond fluorescence spectroscopy (LTRSFS) using specific albumin fluorescent probe and high resolution nuclear magnetic resonance (NMR) 1H spectroscopy.

There were revealed 3 binding sites in albumin molecule with fluorescent decay time of 1, 3 and 9 nanoseconds (A1, A3 and A9 sites, respectively) in healthy volunteers using LTRSFS approach. There was found significant decrease of fluorescent decay time of probe bound to albumin A3 site of FES patients as compared with controls. It points out on the conformational changes in HSA molecule in FES patients. NMR 1H spectra of blood serum and its albumin fraction of healthy donors and FES patients were studied. There were shown clear differences in NMR 1H spectra between these two groups that points out to the conformational changes of albumin molecule in FES patients and disturbances in albumin transport functions. The reaction ability of thiol groups of albumin molecules in FES patients was significantly lower in comparison with healthy persons. It also points out on disturbances of antioxidant albumin properties in FES patients.

High-tech approaches can be useful for the development of new biomarkers for diagnostic and predicting methods and methods for the evaluation of the efficacy of different types of therapy of mental disorders.

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.

Pathogenetic mechanisms of hyperkinetic syndrome (HKS) or attention deficit hyperactivity disorder (ADHD) are not clear.

To elucidate some aspects of monoamine involvement in pathogenesis of disorder and response of monoaminergic systems to psychostimulant medication.

Levels 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).

HKS 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.

Results 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.

The authors have not supplied their declaration of competing interest.

The last years it is became clear that disturbances in molecular processes in pathological conditions can be connected with conformational changes in protein structure.

Investigation of blood albumin conformation in patients with melancholic depression.

There were investigated 19 patients with melancholic depression (12 women and 7 men) and 25 health volunteers. Patient's state according to ICD-10 criteria was defined as a depressive episode in the frame of bipolar depressive disorder (type 2) (F32) and in the structure of recurrent depressive disorder (F33). Subnanosecond laser time resolved fluorescence spectroscopy (SLTRFS) (subnanosecond diapason) with K-35 fluorescent probe was used for the investigation of albumin conformation.

There were revealed 3 binding sites in albumin molecule with fluorescent decay time of 1, 3 and 9 nanoseconds (A1, A3 and A9 sites, respectively) in healthy volunteers using SLTRFS approach. There were found significant differences between albumin binding sites of volunteers and patients with melancholic depression, respectively, А1–117 ± 7 и 142 ± 10; А3–358 ± 14 и 420 ± 26; А9–371 ± 16 и 433 ± 29.

These findings point out that melancholic depression is followed by conformational changes of albumin molecule that can affect its functional properties. We can hypothesized that albumin binding properties can serve as a biomarker of the efficacy of psychopharmacotherapy.

The authors have not supplied their declaration of competing interest.

Pharmacodynamics of serotonergic antidepressants differently influencing on serotonin reuptake receptors is poorly investigated.

To compare biochemical profiles at patients with anxious depression under treatment with tianeptine–serotonin reuptake enhancer and sertraline–selective serotonin reuptake inhibitor.

Platelet monoamine oxidase (MAO) and serum amine oxidase (AO) activities, level of middle mass endotoxic molecules (MMEM) and serum albumin functional properties – effective albumin concentration (EAC) and reserve of albumin binding (RAB) were investigated at 43 patients with anxious depression (F 32.1 and F 33.1). Clinical severity of illness was assessed using Hamilton Depression (21 items) and Hamilton Anxiety Scales. All patients were divided in two groups: group I (21 person) received tianeptine (37, 5 mg/day), group II – sertraline (50 mg/day).

It was established that patients with anxious depression were characterized by significant increase in MAO activity (by 95%) and the level of MMEM (by 86%) and significant decrease in AO activity (by 28%) and EAC and RAB parameters by 43 and 38%, respectively, in comparison with healthy volunteers. Under tianeptine and sertraline treatment, there were revealed contrary directed changes of all investigated parameters.

Results of study show that both tianeptine and sertraline are equally effective in treatment of anxious depression. Present biochemical investigation, however, suggest that underlying biochemical changes are more complete following tianeptine treatment.

The authors have not supplied their declaration of competing interest.

Discovery of biomarkers for evaluation of efficacy of psychopharmacotherapy is important task.

To study parameters characteristic for albumin binding sited in melancholic depression (MD) using fluorescent laser spectroscopy in range of 30–50 picoseconds.

22 patients with MD (dep) (F33.1 and 2) were investigated in dynamics of antidepressant therapy (venlafaxine: 75–150 mg/daily) for 30 days. Control group (con) consists of 54 volunteers. Decay of fluorescence amplitude (A) of fluorescent probe K-35 from serum albumin was measured using laser. Earlier, we revealed 3 binding sites in albumin with amplitudes A1, A2 and A3 with decay time of 1, 3 and 9 nanoseconds, respectively.

There was revealed significant decrease of amplitude A1dep, normalized on mean value of A1 for controls (A1dep/A1con), for patients with MD after treatment with venlafaxine. In this case, A1depvalues decreased and were equal to A1 values of controls (P < 0.01): A1dep/A1con before treatment–1.23 and after 30 days of therapy–0.97 relative units; for controls this value was–1.00 relative units. The same type of normalization was observed for amplitudes A2 and A3 of melancholic patients. There were revealed significant changes of A3/A1 ratio that points out on conformational changes of serum albumin molecule in dynamics of venlafaxine therapy.

We have registered unidirectional changes in albumin molecule in patients with MD. Investigated parameters can serve as potential biomarkers for evaluation of efficacy of psychopharmacotherapy.

The authors have not supplied their declaration of competing interest.

Relevance of current investigation is conditioned by the high prevalence of depression in population and tendency of increased rate of relapses.

To study efficacy of selective serotonin-noradrenalin reuptake inhibitor–milnacipran in treatment of depressive disorders.

There were investigated 22 patients. Patient's state was defined as depressive episode (F32.1) and recurrent depressive disorder (F33.1). Mean age–33 years, duration of disease–from 2 weeks to 18 years, duration of current depressive episode–5.3 months. Mean point according to HAM-D scale before treatment was 24.0. Patients were investigated in dynamics of antidepressant therapy (milnacipran–50–150 mg/daily) for 4–5 weeks.

Efficacy of treatment with milnacipran was 82% (18 responders, 4 nonresponders). In responder's group decrease of depressive symptoms was started after 1 week of treatment and practical reduction of all these symptoms was observed after 4–5 weeks of therapy (points of HAM-D scale–0.81). Patients of this group receive milnacipran as supportive therapy at least for 3 months after signing out of clinic. During 1 year after signing out of clinic, there were no signs of aggravation of patient's state. 2 patients independently discontinue to take the medicine; there were aggravation of state and they were hospitalized in psychiatric clinic.

Milnacipran is effective in treatment of depressive disorders, ensured effective reduction of depressive symptoms. Its therapeutic effect is realized rather quickly. Milnacipran can be recommended as antidepressant of choice for prophylaxis of depressive disorders.

The authors have not supplied their declaration of competing interest.