Diagnosis method for distinguishing the cases of therapeutically resistant reactive depression

FIELD: medicine.

SUBSTANCE: method involves evaluating patient state using Hamilton scale, considering leukocyte formula of general clinical blood analysis to determine leukocyte and monocyte number and determining whole blood infrared spectroscopy absorption spectrum values in infrared analyzer within 30 s in the bandwidth of 3085-2832 cm-1 and 1543-1425 cm-1, respectively. Mean value of depression intensity being equal to 19.0±2.1 points, mean absorption values being equal to 40.5±3.2% and 43.4±2.9% in the bandwidth of 3085-2832 cm-1 and 1543-1425 cm-1, respectively in combination with immunity characteristics like monocytosis>5% and lymphocytosis>25% leukocyte formula of general clinical blood analysis being observed, therapeutically resistant reactive depression cases are to be diagnosed.

EFFECT: high accuracy of diagnosis.

1 tbl

 

The invention relates to medicine, namely to psychiatry and neurology. Depression is one of the most common disorders in psychiatric and somatic practice. More than one-third of patients with depression find resistance to timoanalepticheskoe therapy than due to the need to identify ways that timely and accurate predictions of refractoriness to therapy.

The method improves the accuracy of diagnosis of resistance in reactive depression by determining the biochemical and immunological markers are predictors of refractoriness to antidepressant therapy. During testing identifies persons with pathobiochemical and immunological signs of disorders of the nervous system, which will continue to occur or already manifest at the time of the survey depressive symptoms that are resistant to modern antidepressant psychopharmacological agents. The method provides high accuracy of definition of persons with specified symptoms to clarify the dynamics of the situation in the clinic.

As a prototype of the present invention applicants propose a clinical method for the diagnosis of treatment-resistant depression on the Hamilton depression rating scale [thesis for the academic Art. CMN Pokrovsky became popular Therapy re istotnie depression and metabolic disorders phospholipids (clinical pathobiochemistry aspect). - Tver, 1999. - 25 S.].

Determine the severity of depression on the Hamilton depression rating scale calculates the amount of points. Depression is considered resistant if for two consecutive courses adequate monotherapy pharmacologically different (according to the chemical structure and biochemical effects) antidepressants after 6-8 weeks to acknowledge the absence or lack of clinical effect. During this period, again assessing depression on the Hamilton depression rating scale, and by reducing the number of points less than 50% from baseline classify depression as treatment-resistant. Adequate treatment of reactive depression includes the appointment of a tranquilizer and antidepressant according to clinical indications and characteristics of the spectrum of its psychotropic, neurotropic and somatotropic activity, the use of an appropriate range of doses with growing up with the ineffectiveness of therapy two weeks before maximum or parenteral introduction of and compliance with the terms of course duration of at least 3-4 weeks. This clinical diagnosis method standardizes the group resistant to timoanalepticheskoe therapy of depressed patients, and offers a practical physician procedure and provides continuity in the patient's treatment.

The disadvantages of the prototype, VZG the poison authors, following:

1. The method is subjective, depends largely on the level of specialist training.

2. Cannot identify the intimate neurobiochemical resistance mechanisms of reactive depression therapy.

3. Requires a long time.

In contrast to the above method of the prototype, the proposed new method reveals the average results for a cohort of treatment-resistant patients with reactive depression. Determine the severity of depressive symptoms on the Hamilton depression rating scale (21), which for reactive treatment-resistant depression (TRD) is the average 19,0±score of 2.1. Count leukocyte formula of the General analysis of blood, diagnostically important data monocytosis > 5% and limfozitoza > 25%. Identify indicators absorption (%) infrared spectrum of whole blood in the range 3085-2832 cm-1- 40,5±3.2% and in the range 1543-1425 cm-1- 43,4±2,9%, while the norm is in the range 3085-2832 cm-1- 25,6±0,6%, in the range 1543-1425 cm-1- 29,1±1,1% (table. 1).

The method is as follows. Clinical assessment is carried out in accordance with the ICD-10 criteria for a protracted reactive depression and dysthymia. Determine the severity of depressive symptoms on the Hamilton depression rating scale (21), which sostav the em average 19,0± 2.1 points.

Modern research shows that the immune system by organ-specific immune responses humoral and cell type directly involved in the regulation of nervous systems. In particular, revealed the interactions immunological and clinical parameters in depressive disorders. However it is noted that with the increase in the limitations of mental illness, the role of the immune system in the pathogenesis of depression, and therefore increases the risk of immunodeficiency.

In order to identify immunological markers of resistance to depression therapy leukocyte count formula General clinical blood analysis. Material for General clinical blood analysis is capillary whole blood.

Prepared smear is fixed with methyl alcohol for 5 min, and then stained by Romanovsky - Giemsa. Paint standard, incorporates Azur II, water-soluble yellow eosin, methyl alcohol and glycerin. The working solution of the paints is prepared by dilution of 3 drops of finish paint 1.0 ml of distilled water. The duration of the painting 40 minutes. Stained smears examined under a microscope with oil immersion system (eyepiece 10, the lens 90). To count leukocyte use 11-key counter, record the number of each type of leukocytes in percent.

Detected in the cohort of treatment-resistant patients with reactive depression the average performance of monocytosis > 5% indicate tension phagocytic immunity, lymphocytosis > 25% shows the defect cell component of the immune system, which confirms the heterogeneity and multi-level neurobiochemistry of resistance mechanisms of depression to timoanalepticheskoe therapy.

The definition of resistance in depression, the authors carried out by blood tests by infrared spectroscopy method (X) on the hardware-software complex "Icarus" 9/1 (patent No. 2137126 from 10.09.1999, certification No. 5745). The material for the X - integral capillary blood volume of 0.1 ml, measured by the pipette is placed in the original cell and subjected to spectrophotometrically on agriculture "Icarus" 9/1, 9 optical channels with wavelengths of from 3500 to 930 cm-1within 30 seconds the Study was conducted on all 9 channels, however, the most significant were the key figures in the ranges of channels 3085-2832 cm-1and 1543-1425 cm-1. The device records the percentage transmittance of the optical medium, which is a value inversely proportional to the extinction of the solution. Output information is the absorption index (%) infrared spectrum radiation in any given interval of the spectrum in use is e 30 C. The data obtained in the study of blood in the infra-red spectrum analyzer "Icarus" 9/1, obrabatyvat by the standard method and identify the average results for a cohort of treatment-resistant patients with reactive depression. In the ranges X 3085-2832 cm-1and 1543-1425 cm-1identify indicators absorption and calculate the average absorption. Normal averages absorption in the range X 3085-2832 cm-1- 25,6±0,6, in the range 1543 -1425 cm-1- 29,1±1,1. In treatment-resistant depression is the average absorption in the range X 3085-2832 cm-1- 40,5±3,2%, in the range 1543 -1425 cm-1- 43,4±2,9%.

Table 1.

Change indicators infrared spectrum of blood (in %, M±m) and indicators of immunity in patients with reactive treatment-resistant depression.
The boundaries of the spectral region, cm-1Absorption in % $ OKTreatment-resistant reactive depressionComponents, as defined by the IRS in the bloodIndicators of immunity in treatment-resistant reactive depression
3085-283225,6±0,6 40,5±3,2**phospholipids, cholesterol esters, triglyceridesThe content of lymphocytes more than 25% *The content of monocytes more than 5% *
1543-142529,1±1,143,4±2,9**methylene and methyl groups contained in all components of membranes
Note: *-differences from the norm are significant, p <0,05; ** -differences from the norm are significant, p <0,001

Diagnosis of reactive treatment-resistant depression using X blood of patients based on the detection of high performance infra-red radiation absorption on the channels where the tested chemical bond characteristic of phospholipids and virtually all components of biological membranes (3085-2832 cm-1and 1543-1425 cm-1) [Kesler I. Methods of infrared spectroscopy in chemical analysis. - M.: Mir. - 1964. - 257 C.]. Significant improvements absorption of IR radiation blood of patients in these ranges indicates the increase in the concentration of sphingomyelin, phosphatidylserine and other phospholipid fractions in the blood. Detected with X increasing the concentration of sphingomyelin and other fractions of phospholipids in the blood of patients with reactive resistant depression is associated with severe damage cleto is different membranes. The fact that when mental illness changes the content of phospholipids in the blood, it has been proved in several studies [Morkovkina V.M., Cartelised A.V. Patagonia schizophrenia. - M.: Medicine - 1988. - 255 S.]. It is known that phospholipids are the major structural and functional component of biological membranes, are directly involved in the processes of the transmembrane transfer of all metabolites involved in the processes of excitability of the cell, their energy metabolism, protein biosynthesis, and also act as second messengers. In addition, they act as antioxidants, preventing excessive degree of free oxidation of biologically active substances, as well as proektiruemij pathological effects of peroxides on vital structures of the body. The importance of these points are particularly obvious, as is proved by the intensification of the processes of lipid peroxidation (LPO) in different Genesis of mental illness. It was found that chronic emotional stress, underlying depressive suffering, leads to a state of metabolic intracellular hypoxia due to the predominance of the processes of glycolysis over oxidative phosphorylation, i.e. anaerobism on tissue respiration. Under these conditions, impaired utilization of glucose (glycogen), h is about in turn leads to blocking the formation of amerosport of sphingosine - ceramide. Thus due to the activation of specific transferring enzyme produces increased amounts CM (part of which is spent on increasing the synthesis of the FE and FS), which is gipolipidemiceski source of energy depot in the conditions of intracellular hypoxia. You should also take into account the interconversion of phosphatidylethanolamine and phosphatidylserine by decarboxylation reactions of the latter. This reaction proceeds predominantly in the mitochondrial membranes, which confirms the data exclusively about the importance of aminecontaining phospholipids in the processes of oxidative phosphorylation [Racer E. Bioenergetic mechanisms: new perspectives /Ed. Skulachev V.P.), 1979. - 217 C.]. Thus, detected using infrared spectroscopy, the change in optical density of the blood of patients with treatment-resistant reactive depression in the optical spacing characteristic of phospholipids and other components of biological membranes, associated with the characteristic depression of hypoxic processes and as a consequence pronounced changes in biomembranes. Due to the above identified significant improvements absorption of infrared radiation by the blood of patients in the specified ranges, showing the typical resistant Dept is ASCII increasing the concentration of SFM, FAA and FS in the blood, can be used to diagnose reactive treatment-resistant depression.

Study included 75 patients with reactive depression, 40 women and 35 men from 22 to 50 years, average age 35±3.6 years. The results timoanalepticheskoe therapy patients were divided into responders (36 patients), found a positive trend, and the responders (39 patients), have significant positive shifts in the process of therapy is not marked. Clinical studies met the ICD-10 criteria, supplemented by depression scale M Hamilton (21 issues). The control was a group of 50 healthy individuals of comparable age and sex. Laboratory studies included a leukocyte count of clinical blood analysis, combined with an average absorption (%) infrared spectrum of whole blood in the range 3085-2832 cm-1and in the range 1543-1425 cm-1.

The advantages of this method for the diagnosis of treatment-resistant reactive depression:

1. The proposed method allows to assess the dynamics of paired species metabolism in organ, tissue, cellular and subcellular levels.

2. When used in the clinic will discover pathobiochemical and immunological markers of treatment resistance reactive depr the hurt.

3. The use of the claimed method will allow you to control biochemical and immunological levels of the patient's condition, objectivesare clinical assessment of monitoring the effectiveness of treatment.

4. The diagnostic method is easy to use, suitable for use in the clinical setting.

CLINICAL EXAMPLE. Patient N., 43 years. Case history No. 615. Diagnosis: Dysthymia. The disease is associated with long objectively insoluble stressful situation. Clinically detects signs of a depressive episode moderate degree. The severity of depression scale M Hamilton is 21.5 points. Clinical blood analysis revealed lymphocytosis - 27% and monocytosis - 6%. A blood sample was investigated X in the range 3085-2832 cm-1the rate of absorption of 42.8%, in the range 1543-1425 cm-1absorption - of 45.7%. On the basis of the obtained data revealed treatment-resistant reactive depression.

Method for the diagnosis of treatment-resistant reactive depression, including the assessment of the condition of the patient on the Hamilton depression rating scale, characterized in that reveal the presence of monocytosis and limfozitoza, within 30 to determine the performance of infrared absorption spectroscopy of blood in the infra-red spectrum analyzer in the range 3085-2832 cm-1and 1543-1425 cm-1R is schityvat average absorption and with the average severity of depression 19,0±score of 2.1, the value of the average absorption 40,5±3,2% and 43.4±2.9% in the ranges 3085-2832 cm-1and 1543-1425 cm-1accordingly, in combination with indicators of immunity in the form of monocytosis >5% and limfozitoza >25% in the leukocyte formula common blood diagnosed with treatment-resistant reactive depression.



 

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