Update on the neurodevelopmental theory of depression: is there any ‘unconscious code’?

Abstract

Depression is currently one of the most common psychiatric disorders and the number of patients receiving antidepressant treatment is increasing every year. Therefore, it is essential to understand the underlying mechanisms that are associated with higher prevalence of depression. The main component leading to the change in functioning, in the form of apathy, anhedonia, lack of motivation and sleep disturbances, is stress. This is the factor that in recent decades—due to the civilization speed, dynamic technological development as well as competitiveness and competition in relationships—significantly affects the psychophysical condition, which results in an increase in the prevalence of civilization diseases, including depression. To understand the mechanism of susceptibility to this disease, one should consider the significant role of the interaction between immune and nervous systems. Their joint development from the moment of conception is a matrix of later predispositions, both associated with the mobilization of the proinflammatory pathways (TNFα, IL-1β, IL-6) and associated with psychological coping with stress. Such an early development period is associated with epigenetic processes that are strongly marked in prenatal development up to 1 year of age and determinate the characteristic phenotype for various forms of pathology, including depression. Regarding the inflammatory hypothesis of depression, interleukin 17 (IL-17), among other proinflammatory cytokines, might play an important role in the development of depressive disorders. It is secreted by Th17 cells, crossed the placental barrier and acts on the brain structures of the fetus by increasing IL-17 receptor levels and affecting the intensity of its signaling in the brain.

A Review of the Global Impact of the COVID-19 Pandemic on Public Mental Health, with a Comparison Between the USA, Australia, and Poland with Taiwan and Thailand

“…The presence of the “cytokine storm” in severe cases of COVID-19 emphasizes the significance of immunological mechanisms in the pathophysiology of this disease [ 31 , 32 ]. Mindful of the inflammation theory of depression [ 33 , 34 ], elevated pro-inflammatory cytokines might be a nexus in the shared pathology of these diseases. Fetal and early childhood exposure to viral infections enhances the risk of developing psychiatric disorders [ 35 , 36 ].…”

Gender Differences in Complete Blood Count and Inflammatory Ratios among Patients with Bipolar Disorder

“…Even if the etiopathogenesis of BD has not been clarified yet, an interaction between genetic and environmental risk factors seems highly plausible. The literature extensively demonstrated that the immune and inflammatory systems may play a crucial role in determining the onset and recurrence of major depressive disorder (MDD) [31,32]. Thus, the hypothesis of neuroinflammatory mechanisms in the etiology of BD has gained growing credibility [33,34].…”

Plasma concentrations of granulocyte colony-stimulating factor (G-CSF) in patients with substance use disorders and comorbid major depressive disorder

“…Previously, it has been reported that the gene expression of IL-17, IL-21, IL-23, and IL-35 was substantially higher in patients with MDD than in controls, which suggests that the expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. Additionally, these cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain and may be markers and new potential therapeutic targets for recurrent depressive disorders 31 , 32 .…”