RU2644636C1 - Method for prediction of comorbid anxious disorder in patients with recurrent depressive disorder - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention is a method for prediction of comorbid anxious disorder in patients with recurrent depressive disorder, characterized by determination of cortisol and dehydroepiandrosterone sulfate (DHEAS) neurosteroid content in the blood, as well as phagocytal activity of leukocytes, and at cortisol concentrations above 850 nmol/l, ratio of DHEAS/cortisol below 3.5 and phagocytal index below 55%, comorbid anxious disorder is predicted in patients with recurrent depressive disorder.

EFFECT: possibility of prediction of comorbid anxious disorder in patients with recurrent depressive disorder.

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Description

The invention relates to medicine, namely to psychiatry, and can be used to predict comorbid anxiety disorder in recurrent depressive disorder.

This method is based on the assessment of hormonal and immunological factors involved in the pathogenesis of depressive disorders.

A known method of differential rapid diagnosis of anxiety and depressive disorders, based on a neuropsychological study of memory, attention, performing functions with visual and auditory stimuli, followed by their reproduction after 10 minutes (5). A method for predicting anxiety and depressive disorders in patients with myocardial infarction involves a comprehensive biochemical study of the patient’s blood counts and determination of caspase-3 activity, and with a value of norepinephrine 0.77 ± 0.02 μg / L or higher, dopamine 0.51 ± 0.01 μg / L and higher, caspase-3 activity above 1.02 ± 0.041 pmol / min / ml predict the development of anxiety-depressive disorders in the first month of the post-infarction period (4). There is also a method for evaluating the effectiveness of treatment and predicting the risk of recurrence during depressive disorders by assessing the condition of patients on a Beck and Hamilton depression scale in points, conducting a time recognition test in points before treatment, on days 14 and 28 of treatment, characterized in that these days additionally record the individual minute indicator in seconds (3). A method for assessing the severity of the current depressive episode in patients with recurrent depressive disorder is carried out by determining the GSK-3β / β-actin ratio, calculating the total score on the SIGH-SAD scale (6).

An adequate prototype of the proposed invention, allowing to predict comorbid anxiety disorder with recurrent depressive disorder, was not found in the analyzed literature.

The task of the invention is the prediction of comorbid anxiety disorder in patients with recurrent depressive disorder.

The task is achieved by assessing the content of neurohumoral blood parameters: the concentration of the hormone cortisol, the neurosteroid dehydroepiandrosterone sulfate (DHEAS), as well as by determining the phagocytic index in the test system with melanin formaldehyde latex. At a cortisol concentration above 850 nmol / L, a DHEAS / cortisol ratio below 3.5 and a phagocytic index value below 55%, comorbid anxiety disorder is predicted in patients with recurrent depressive disorder.

New in the proposed method are the use of determining the concentrations of cortisol and DHEAS, as well as their ratio, together with the determination of the phagocytic index as biological predictors of comorbid anxiety disorder in case of recurrent depressive disorder, and, as a consequence, the most unfavorable course of depression.

The researchers' close attention to the problem of comorbidity of depressive and anxiety disorders is due to their widespread prevalence in the population. Thus, according to the results of epidemiological studies in the USA (Epidemiologic Catchment Area study), comorbid anxiety disorder is detected in approximately 50% of patients with a diagnosis of "major depression" (20). On the other hand, nearly 60% of patients with anxiety disorders suffer from depression (17). In bipolar depression, anxiety disorders are more common than in unipolar depression (10). It is known that the combination of depressive and anxiety disorders leads to an increase in clinical symptoms, significantly worsens the short-term and long-term prognosis of both disorders, increases the frequency of suicidal attempts and the risk of premature termination of drug therapy by patients, and also worsens the therapeutic response to antidepressant treatment (9; 11; 14) . As a result of the mutual influence of depressive and anxiety disorders during their comorbidity, the clinical characteristics, course and prognosis of the disease, and, accordingly, treatment tactics, change.

Thus, the comorbidity of depressive and anxiety disorders is not only a purely medical, but also a serious socio-economic problem. Issues with regard to patterns, clinical significance, factors in the formation of comorbid relationships between these disorders remain insufficiently studied (12; 21). Therefore, it seems relevant to search for biological markers of the formation of comorbid anxiety disorder in individuals with recurrent depressive disorder.

The diagnostic and prognostic significance of the basic constitutional characteristics of patients with these disorders, as well as the level of social adaptation and the effectiveness of SSRIs in the treatment of this cohort of patients are not fully defined. Modern research suggests that the immune system is actively involved in the pathogenesis of depression (13; 15). In recent years, new information has been obtained on the relationship between the parameters of depression, anxiety and immunity (18; 22). Correlations were found between immunological parameters and clinical parameters: the depth of depression, the effectiveness of therapy (2; 15; 16). Previous data showed that people with depressive disorders are characterized by signs of an inflammatory process. The analysis of immunological parameters showed that the following indicators are most informative: level of CD4 ⁺ lymphocytes, phagocytic index. One of the key mechanisms of depressive and anxiety disorders is neurohumoral regulation, closely associated with neuroplasticity (7). Hormones of the pituitary-adrenal system (in particular, cortisol), neurosteroids (e.g., dihydroepiandrosterone sulfate - DHEAS) and neurotransmitters change dynamically during the pharmacotherapy of affective disorders (8), taking into account biological indicators such as cortisol and DHEAS can also predict the response to antidepressant in patients with comorbid depressive and anxiety disorders (7).

In this regard, the determination of the content of cortisol and dehydroepiandrosterone sulfate in the blood serum and their ratio, as well as the value of the phagocytic index, have prognostic and diagnostic value.

The application of the proposed method allows to improve the quality of medical care for patients with comorbid recurrent depressive disorder and anxiety disorder without additional economic costs, to reduce social consequences due to a more differentiated approach to the treatment of patients with these disorders. The use of this method also helps to increase the compliance of patients and their level of social adaptation. Since the method is simple to implement, it can be widely used in clinical practice.

New features showed in the claimed combination of new properties that are not explicitly derived from the prior art in this field and are not obvious to a specialist. An identical set of features was not found in the patent and medical literature. The proposed method can be used in practical health care to improve the accuracy of diagnosis and the selection of adequate treatment.

Based on the foregoing, the proposed invention should be considered relevant to the conditions of patentability: “Novelty”, “Inventive step”, “Industrial applicability”.

The invention will be clear from the following description.

The proposed criteria (cortisol content, DHEAS and their ratio, phagocytic index) were obtained as a result of a clinical and biological examination of patients with depressive disorders who underwent treatment in the Department of Affective Conditions of Clinics of the Research Institute of Mental Health of the Tomsk National Research Medical Center of the Russian Academy of Sciences.

Using the proposed method, patients (n = 25) were examined who were admitted to the Department of Affective Disorders of the Clinic of the Scientific Research Institute of Mental Health with a verified diagnosis of recurrent depressive disorder comorbid with an anxiety disorder according to ICD-10 criteria. In the study group, women predominated - 80% (n = 20). The average age of patients was 45.5 ± 12.7 years. Depending on the severity of the current depressive episode, the patients in the study sample were as follows: mild depressive episode in 16% of cases (n = 4), moderate depressive episode - 68% (n = 17), severe depressive episode - 16% (n = 4 ) In the spectrum of anxiety disorders, panic disorder was more common - 56% (n = 14), in other cases, generalized anxiety disorder was diagnosed - 28% (n = 7), other mixed anxiety disorders - 8% (n = 2), agoraphobia with panic disorder - 4% (n = 1) and social phobia - 4% (n = 1).

The following psychometric tools are used as standardized tools for assessing the severity of depression and anxiety, the severity of the disease, the level of social adaptation in the examined patients, as well as for objectifying the dynamics of the clinical characteristics of depressive and anxiety disorders during treatment with antidepressants: Beck depression self-assessment scales and Shihan anxiety, Hamilton Depression Scale (HDRS-17), Hamilton Anxiety Scale (HARS), Global Clinical Impression Scale (CGI), Evaluation Scale for Side Effects (UKU) and Social Adaptation Self-Assessment Scale (SASS).

Molecular biological and immunological parameters are compared in patients of 2 groups: with recurrent depressive disorder, comorbid course with anxiety disorders, and recurrent depressive disorder without comorbid anxiety disorder.

The study of hormones in the hypothalamic-pituitary-adrenal system (Table 1) revealed a significantly high level of cortisol concentration in patients with comorbid depressive and anxiety disorders compared with this indicator in the group of patients with depressive disorders (p = 0.049). Patients with comorbid depressive and anxiety disorders are characterized by a lower content of DHEAS compared with a group of patients with recurrent depressive disorder, the differences do not reach the level of statistical significance. The DHEAS / cortisol ratio, which characterizes the anabolic-catabolic balance and the body's resistance to various disorders (1; 8), is significantly reduced in patients with comorbid depressive and anxiety disorders compared with the values in the group of patients with depressive disorders (p = 0.047). Probably, these differences indicate a depletion of the anabolic capabilities of the body, an increase in clinical symptoms and a worsening prognosis of both disorders.

When studying the parameters of immunity in a group of patients with comorbid recurrent depressive disorder and anxiety disorders, a significant decrease in the phagocytic activity of leukocytes was established in comparison with patients with recurrent depressive disorder (Table 1).

Recurrent depressive disorder with comorbid anxiety disorder is characterized by changes in the immunological parameters and hormone content of the hypothalamic-pituitary-adrenal system, which can serve as an important diagnostic and prognostic factor in assessing the course of recurrent depressive disorder, comorbid with anxiety disorders.

We give clinical examples as an illustration.

Example 1 (recurrent depressive disorder).

Patient S., b. 1962 Diagnosis: Recurrent depressive disorder, mild depressive episode with somatic symptoms F33.11

Complaints of reduced mood, feelings of anxiety, melancholy, weakness, apathy, loss of pleasure, joy, desire to communicate with people, decreased appetite, sleep disturbance, increased blood pressure to 170/80 mmHg, despite the regular use of antihypertensive drugs.

The heredity is burdened: the patient’s mother was treated at the NIIPZ clinic in connection with depressive disorder. The patient was born in Kazakhstan, the youngest of 3 children. Grew a healthy child, developed in accordance with age. Has a secondary special education, the profession of merchandiser. Currently works as a registrar in a clinic. She was married, the last 12 years in a divorce. From marriage, has 2 adult daughters (27 years and 31 years). He lives with his youngest daughter in the same apartment. In the obstetric history of 11 medical abortions, menopause at 42 years old with autonomic symptoms. From 42 years old, GB suffers. Operations under general anesthesia: at age 45 for appendicitis, at age 50 - removal of the thyroid gland. Regularly takes: lorista 50 / day; concor 5 mg / day .; cardiomagnyl 75 mg / day; eutirox 100 mcg / day For the first time at the age of 20, for no apparent reason, she noted a decrease in mood, apathy, anxiety, sleep disturbance, and she could hardly cope with workloads. I did not go to the doctors, after a year the symptoms decreased on my own. Subsequently, she repeatedly suffered depressive episodes of mild to moderate severity. Turned to psychiatrists, received treatment without effect. The real deterioration during the year, on appeal, was hospitalized at the clinic of the Scientific Research Institute of Mental Health.

Mental status at admission: Outwardly neat. The expression is tired. Sits in a closed position. The conversation is tense. Mimicry is smoothed out, no gestures. The voice is low, with modulations. Answers the questions essentially after a short pause. Complaints of reduced mood, anxiety, longing, loss of appetite, body weight (lost 4 kg), weakness, apathy, loss of pleasure, desire to communicate with people, sleep disturbance. The mood is lowered. There are diurnal mood swings with some improvement in the evening. He understands logical and grammatical constructions correctly. The Krepelin account performs with one error. Deceptions of perception, suicidal thoughts, periods of uplift denies.

The leading syndrome is anxiety-depressive.

Laboratory examination: serum cortisol level - 714.33 nmol / L, DHEAS concentration - 27.72 μmol / L, DHEAS / cortisol ratio - 3.88, PHI - 56%.

Treatment: elitsea 10 mg / day, teralen 5 mg / day, phenazepam 0.5 mg / day, mildronate 10.0 w / w, No. 7, Mexiprim 2.0, v / m, No. 10, physiotherapy, psychotherapeutic complex.

Mental state at discharge: Against the background of treatment, the mood improved, the feeling of anxiety, melancholy were reduced, sleep and appetite were restored, blood pressure stabilized.

Example 2 (recurrent depressive disorder with comorbid anxiety disorder).

Patient Z., born in 1970 Diagnosis: Recurrent depressive disorder, mild depressive episode with somatic symptoms F33.11. Comorbid: Panic Disorder, F41.0

Complaints of reduced mood, anxiety, melancholy, lack of appetite, severe weakness, guilt, heaviness and discomfort in the body, apathy, loss of pleasure, joy from usually pleasant activities, bouts of fear accompanied by a heartbeat, shortness of breath, tinnitus, sweating.

Heredity is psychopathologically burdened: the daughter has an eating disorder since adolescence. Born in a complete family, the eldest of 2 children. Grew a healthy child. Received secondary medical education. She worked as a midwife for 20 years, and currently works as a nurse. Married, relationship with spouse is complicated. From marriage has an adult daughter. Since 28 years old he suffers from hypertension, in recent years he regularly takes lisinopril 5 mg / day, bisoprolol 5 mg / day. At 41, she underwent surgery under general anesthesia - removal of the uterus in connection with myoma.

For the first time in 43 years, against the background of a traumatic situation (daughter’s disease), depressive symptoms developed: mood decreased, apathy, a sense of hopelessness, anxiety appeared. To alleviate the condition, she began to resort to alcohol. Depressive symptoms reduced after 3-4 weeks on their own, but the patient continued to drink alcohol (drank 2 times a week for a bottle of beer, then daily 0.5 l, sometimes 1 liter of beer). After 2 years, the patient stopped alcoholization. Since the spring of 2015 (45 years old), the condition gradually began to worsen: mood and appetite decreased, sleep disturbed, lost a sense of joy, pleasure, there was no desire to communicate with people. There was a fear of the presence of cancer. In search of cancer, she was comprehensively examined. In July 2015, for the first time at night, a panic attack developed with a strong heartbeat, shortness of breath, tinnitus, sweating, a feeling of heat in the whole body, and a fear of dying. Subsequently and until now, seizures worry about 2-3 times a week. Depressive symptoms increased: appetite disappeared, weight began to decrease (for 8 months she lost 23 kg), she limited her social circle, her attention became distracted, and it became more difficult to cope with duties at work. A month ago, she began to take grandaxin 100 mg / day on her own, without effect. On appeal, she was hospitalized in the 3rd department of the Scientific Research Institute of Mental Health.

Mental status at admission: Outwardly neat. Sits in a closed position. During the conversation, the pose rarely changes. Gesticulation is absent. Tense. Mimicry is smoothed, mainly expresses fatigue, anxiety. The voice is not loud, slightly modulated. Complaints of reduced mood, anxiety, longing, apathy, loss of appetite, severe weakness, guilt, heaviness and discomfort in the body, dizziness, bouts of fear, sleep disturbance. Reports that she has lost her sense of pleasure, joy and desire to communicate with people. Subjectively, the mood evaluates to "2". About 2-3 times a week, anxiety attacks worry, accompanied by a strong heartbeat, shortness of breath, tinnitus, sweating, a sensation of heat throughout the body. During an attack, he is afraid of losing consciousness or dying. The duration of attacks is 5-10 minutes. He notes difficulties in concentrating, inability to clear thinking, slowing down thinking. In this regard, it has become more difficult to cope with duties at work. Periods of uplifting with an increase in overall energy throughout life, deceptions of perception, denies suicidal thoughts.

The leading syndrome is anxious and depressive.

Laboratory examination: serum cortisol level - 956.96 nmol / L, DHEAS concentration - 3.40 μmol / L, DHEAS / cortisol ratio - 0.35, PHI - 44%.

In this case, the concentration of cortisol is higher than 850 nmol / L, the ratio of DHEAS / cortisol is lower than 3.5 and the phagocytic index value is lower than 55% confirm the presence of comorbid anxiety disorder.

Treatment: paxil 20 mg / day, ketylept 50 mg / day, intravenous iv (cap) 10 mg, lisinopril 5 mg / day, bisoprolol 5 mg / day.

Mental state at discharge: Against the background of treatment, the feeling of anxiety, panic attacks, irritability, mood improved, became more active, the desire to communicate with people returned, night sleep, appetite were restored.

Proposed as an invention, the method was tested in 25 patients. The method is simple to implement and based on the determination of the concentration of cortisol and dehydroepiandrosterone sulfate and their ratio, as well as the determination of the phagocytic index, it is possible to predict comorbid anxiety disorder in patients with recurrent depressive disorder and to purposefully carry out rehabilitation psychotherapeutic and pharmacological measures.

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Claims (1)

A method for predicting comorbid anxiety disorder in patients with recurrent depressive disorder, characterized in that the blood of patients determines the content of the hormone cortisol and the neurosteroid dehydroepiandrosterone sulfate (DHEAS), as well as the phagocytic activity of leukocytes, and at a concentration of cortisol above 850 nmol / l, the value of the ratio DHE cortisol below 3.5 and a phagocytic index value below 55% predict comorbid anxiety disorder in patients with recurrent depressive disorder.