Adjustment disorder (AD) is one of the most common mental disorders. Considering the social and economic situation in Ukraine at present, almost 50% of the population has symptoms of mental health disorders, and this number tends to increase 1. Personally significant stressful life events, even short-term, affect both the mental and physical health of the individual. Individual risk factors are particularly important for the development of the AD, including the experience of significant stress in childhood, problems with mental health in the past, and challenging life circumstances.

The most significant combination of factors is the presence of provoking agents (individually substantial types of stressful life events) combined with an individual response (stress vulnerability) and constant personal difficulties in combination with other aversive social and psychosocial factors of vulnerability (low self-esteem, self-blame, pessimism) 2,3. It should be noted that the fuzzy separation between different manifestations of the AD and normal adaptive responses is difficult to diagnose 3,4 Therefore, the diagnosis and treatment of adjustment disorder is extremely relevant.

The ICD-10 indicates that a predisposition or individual vulnerability plays the more significant role in the onset of the AD than in other disorders of the same cluster (F43). This association implies a kind of "stress-vulnerability syndrome" that usually declines social or professional functioning, even if it doesn’t correspond to the diagnostic group.

In the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-5) 5, the chapter "Trauma and Stress Disorder Disorders" combines anxiety disorders preceded by an anxiety or traumatic event and clearly identifies the criteria for a traumatic event. Special attention is paid to sexual violence. Adaptive disorders are redefined as an array of stress response syndromes that occur after contact with an alarm event.

According to DSM-5 criteria, for AD diagnosis emotional or behavioral symptoms should develop within three months after identifiable stress had taken place (A). Symptoms or behavior are clinically significant, as evidenced by one or both of the following (B):

A stress-related disorder does not meet the criteria of another mental disorder and is not simply an aggravation of a pre-existing mental disorder (C). Symptoms do not represent a normal bereavement (D). After the termination of the stressor (or its consequences), the symptoms persist for no more than 6 additional months (D) 5, 6.

Symptoms may include: a feeling of sadness, hopelessness or lack of enjoyment with the things you used; frequent crying; feeling of anxiety, nervousness, stress; problems with sleep; lack of appetite, concentration of attention; a sense of congestion; difficulties in daily activities; a sense of lack of social support; avoidance of important things (such as work or paying bills); suicidal thoughts or behavior. The persistent or chronic AD can last more than 6 months, especially if the stressor continues, for example, in case of unemployment. Many publications note that AD is most often (up to 37%) observed in primary health care facilities and outpatient psychiatric practice 7,8. The AD has high co-morbidity with depression, anxiety, mixed anxiety-depressive states, behavioral disorders, substance abuse.

AD occurs when the need for adaptation exceeds the ability of a person to maintain a psychological or physiological balance. Adaptation at the physiological level is associated with the activity of monoamine neurotransmitters, hormones (e.g., glucocorticoids) and other neuromodulators that affect several areas of the brain and various organ systems 16. Excessively high or low levels of glucocorticoids lead to neuronal atrophy, especially in the hippocampus, amygdala and prefrontal cortex (PFC), negatively affecting the grey matter volume in this regions. The disturbance in the PFC activation causes a deficit in the prefrontal cortical function and anomalies in the metabolism of mesocortical dopamine (DA), which leads to hyperactivation of the amygdala, hippocampus, and locus coeruleus. Such changes can provoke hypothalamic–pituitary–adrenal axis hyperactivation, disrupt the metabolism of serotonin, enkephalins, glutamate, etc., and promote the development of mental and behavioral disorders 17. At the same time, a decrease in the effect of PFC on subcortical reactions potentiates the development of new stress reactions, affects the specific behavior of the individual, including sleep, impulsivity or isolation, autonomic responses, movements and sensitivity to pain. Any of these symptoms may be due to an uncontrolled or excessive reaction to stress. For example, loss of control over suicidal impulses may be associated with a decrease in the availability of serotonin and an increase in serotonin-2A receptor activity 18. Serum levels of protein carbonyl groups and nitrosylated proteins, which are biological markers of oxidative stress, have been studied 19. Biomarkers have been identified, suggesting the direct role of oxidative stress in regulatory disorders.

At the same time, pathogenetically approaches to AD therapy are not fully understood 16, 20. The studies on AD treatment have revealed an excessive use of different classes of antidepressants without taking into account the concept of time-limited AD 16,20. A retrospective analysis aimed at evaluating the effectiveness of antidepressants in patients with AD did not show any difference in the clinical response to any particular antidepressant. The primary statistical difference consisted in the frequency of responses when patients diagnosed with AD were twice as likely to respond to standard antidepressant treatment (approximately 70% of cases) than patients diagnosed with depression. It was found that all antidepressant are equally effective and more efficient than other agents in the treatment of AD, while drugs combinations can increase the risk of possible side effects 21. The presence of suicidal risk in patients with a this diagnosis requires the choice of the safest treatment.

Modern pathogenetically oriented therapy of AD should be targeted on neurotransmitter causes and use systemic therapeutic approach, taking into account, first of all, the safety of the drugs. In this aspect, in our opinion, the use of new classes of regulatory medications looks promising. Regulatory peptides have a wide spectrum of biological activity, which is of great importance in coordination of body functions, because of neuroendocrine, immunological, cellular and molecular interactions 23. Regulatory peptides are related to the endogenous body compounds that bind the basic biochemical systems of the body and mediate the reactivity of the organism to various external factors. Exposure to negative environmental factors can increase the effects of regulatory peptides 24. The advantage of peptide preparations is the extremely low probability of toxicity when administered even in large doses, since the products of their metabolism are natural amino acids that perform mainly homeostatic functions, which significantly reduces the likelihood of side effects. Selank (synthesized analogue of the endogenous regulator of immunity – taftcin) is one of the promising regulatory peptides in the AD treatment. Since it has an original mechanism of neurospecific action on the central nervous system, it affects the exchange of monoamines in the emotiogenic structures of the brain (hypothalamus, limbic system) and the activity of brain enzymes tyrosine and tryptophan hydroxylase 25. Anxiolytic and antidepressant action of “Selank” is associated with regulation at the genome level of the synthesis and metabolism of norepinephrine, serotonin, and enkephalins in the emotional zones of the brain. “Selank” stabilizes the processes of excitation and inhibition in the brain and increases the stability of neurons of the cerebral cortex to functional loads of high intensity 26. Thus, the complex action of the regulatory peptide, including neurometabolic, anxiolytic, psycho-stimulating effects, reducing asthenic symptoms and normalizing mental activity 27, allows it to be used in the therapy of AD.

The authors have no conflicts of interest to declare.