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<p>Chronic stress, which disrupts the cerebral and peripheral mechanisms of long-term adaptation, plays a key role in the development of affective disorders. Impaired adaptive mechanisms are apparent as excessive and/or adverse reactions to stressful situations. The aim of the present study was to deepen our understanding of the role of chronic stress in the pathogenesis of depression by carrying out a comparative analysis of psychometric and peripheral biochemical parameters in depressed patients with and without chronic stress in order to identify specific markers of these conditions and potential therapeutic targets. The study included 324 individuals (224 women, 80 men) with unipolar depressive disorder, 187 of whom had experienced chronic stress in the year prior to testing. Patients with depression and concomitant chronic stress were shown to have a specific biochemical and immunological profile reflecting the influence of chronic stress on the cerebral regulation of adaptive mechanisms. In particular, depletion of the adaptive systems (hypothalamic-pituitary-adrenocortical and immune) was apparent as significantly lower levels of free cortisol in saliva and lymphocytes in the blood, while the serum level of active vitamin D, which has neuroprotective, anti-inflammatory, and antioxidant effects, was reduced. The elevated levels of folates detected in patients with chronic stress may reflect disturbances in their metabolism and their interaction with vitamin D metabolism. A mathematical model was created to assess the likelihood of developing depression associated with chronic stress. According to this model, a combination of low levels of free salivary cortisol, blood lymphocytes, and active vitamin D, and high serum vitamin B9 levels may constitute a risk factor for the development of depressive symptoms in conditions of chronic stress. With a cutoff point of 0.75, the sensitivity of the model was 78% and the specificity was 71%. These results not only reflect the neurohumoral and immune mechanisms at the intersection of chronic stress and mood disorders, but may also form the basis for the development of more effective treatments and prevention strategies for depressive states.</p>

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Specific Peripheral Markers of Chronic Stress Load in the Pathogenesis of Depression: a Clinical Study

  • 期刊论文

  • 发表日期：

    2026年2月25日

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  • T. A. Druzhkova,
  • M. Yu. Zhanina,
  • Yu. E. Bryzgalova,
  • S. B. Popova,
  • A. B. Guekht,
  • N. V. Gulyaeva

摘要

Chronic stress, which disrupts the cerebral and peripheral mechanisms of long-term adaptation, plays a key role in the development of affective disorders. Impaired adaptive mechanisms are apparent as excessive and/or adverse reactions to stressful situations. The aim of the present study was to deepen our understanding of the role of chronic stress in the pathogenesis of depression by carrying out a comparative analysis of psychometric and peripheral biochemical parameters in depressed patients with and without chronic stress in order to identify specific markers of these conditions and potential therapeutic targets. The study included 324 individuals (224 women, 80 men) with unipolar depressive disorder, 187 of whom had experienced chronic stress in the year prior to testing. Patients with depression and concomitant chronic stress were shown to have a specific biochemical and immunological profile reflecting the influence of chronic stress on the cerebral regulation of adaptive mechanisms. In particular, depletion of the adaptive systems (hypothalamic-pituitary-adrenocortical and immune) was apparent as significantly lower levels of free cortisol in saliva and lymphocytes in the blood, while the serum level of active vitamin D, which has neuroprotective, anti-inflammatory, and antioxidant effects, was reduced. The elevated levels of folates detected in patients with chronic stress may reflect disturbances in their metabolism and their interaction with vitamin D metabolism. A mathematical model was created to assess the likelihood of developing depression associated with chronic stress. According to this model, a combination of low levels of free salivary cortisol, blood lymphocytes, and active vitamin D, and high serum vitamin B9 levels may constitute a risk factor for the development of depressive symptoms in conditions of chronic stress. With a cutoff point of 0.75, the sensitivity of the model was 78% and the specificity was 71%. These results not only reflect the neurohumoral and immune mechanisms at the intersection of chronic stress and mood disorders, but may also form the basis for the development of more effective treatments and prevention strategies for depressive states.