For the first time, an integrative concept for the diagnosis of cognitive impairment in MDD (algorithm, criteria and tests) was proposed, which combines neuropsychological parameters and changes in biological markers. The idea of the role of cognitive disorders as a structural component of MDD was further developed. It was shown that the influence of cognitive impairment on the severity of the depressive episode and the degree of dysfunction of patients is not inferior to the influence of its key characteristics. For the first time, the features of the dynamics of disorders in different cognitive domains depending on the overall severity of the episode of depression were described. Thus, attention disorders deepen with the increasing severity of a depressive episode; memory impairment increases significantly only in patients with a severe depressive episode; the severity of executive dysfunction is the same at all levels of depressive episode. It was shown for the first time that cognitive impairment in the active phase of MDD is represented by pathogenetically related disorders of working memory, voluntary attention and executive functions, which together with hypothymia, anhedonia, anxiety, and negative cognitive distortions form a single cognitive-emotional syndrome. For the first time, the significance and specificity of cognitive impairments, along with other symptoms of depression, were assessed for various aspects of functioning in the Ukrainian population of patients with MDD. It was established that neurocognitive impairments are the main predictor of decreased work functioning, and along with the key symptoms of a depressive episode determine the level of general and social functioning. The main cognitive syndrome that negatively affects the work, social, family and general functioning of patients with MDD is the deterioration of working memory. The reduction of executive functions makes an additional contribution to the disruption of work functioning. For the first time, the diagnostic significance of elevated serum IGF-1 levels for the separation of patients with active depressive episodes from healthy individuals in both the general population and different age cohorts was investigated. For the first time, the correlations of peripheral hyperexpression of IGF-1 with cognitive dysfunction was shown to be comparable to or predominant in the relationship of this neurotrophin with key clinical manifestations of a depressive episode. The idea of the marker role of serum BDNF levels for the diagnosis of exacerbation of MDD and the severity of cognitive impairment in its clinical structure was further developed. It was found that a significant decrease in the concentration of BDNF serum is a marker of the active phase of MDD, and the normalization of BDNF indicates the effectiveness of treatment. The degree of BDNF reduction is mainly related to the severity and duration of depressive episode, as well as the severity of attention deficit and memory problems. For the first time, the combination of serum BDNF and IGF-1 has been shown to provide a more accurate differentiation of patients with a depressive episode from healthy individuals than BDNF and IGF-1 separately. The idea of the effectiveness of antidepressant therapy on cognitive functions in MDD was further developed. Cognitive and functional impairments in individuals with MDD were significantly improved, along with regression of the overall severity of the depressive episode, with pharmacotherapy with vortioxetine and escitalopram. At the same time, it was obtained that the use of vortioxetine leads to a statistically significant higher increase in cognitive and functional parameters compared with escitalopram. For the first time, it was shown that the positive dynamics of cognitive impairment during treatment in patients with MDD has a key impact on the restoration of overall functioning and is one of the most important factors in the restoration of functioning in the workplace. For the first time, it was demonstrated that both treatments with vortioxetine and escitalopram (for eight weeks) normalize serum IGF-1 and BDNF levels.
