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.

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.

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.

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.