An immune gate of depression – Early neuroimmune development in the formation of the underlying depressive disorder

Abstract

The prevalence of depression worldwide is increasing from year to year and constitutes a serious medical, economic and social problem. Currently, despite multifactorial risk factors and pathways contributing to depression development, a significant aspect is attributed to the inflammatory process. Cytokines are considered a factor activating the kynurenine pathway, which leads to the exhaustion of tryptophan in the tryptophan catabolite (TRYCAT) pathway. This results in the activation of potentially neuroprogressive processes and also affects the metabolism of many neurotransmitters.

The immune system plays a coordinating role in mediating inflammatory process. Beginning from foetal life, dendritic cells have the ability to react to bacterial and viral antigens, stimulating T lymphocytes in a similar way to adult cells. Cytotoxicity in the prenatal period shapes the predisposition to the development of depression in adult life. Allostasis, i.e. the ability to maintain the body’s balance in the face of environmental adversity through changes in its behaviour or physiology, allows the organism to survive but its consequences may be unfavourable if it lasts too long.

As a result, Th lymphocytes, in particular T helper 17 cells, which play a central role in the immunity of the whole body, contribute to the development of both autoimmune diseases and psychiatric disorders including depression, as well as have an impact on the differentiation of T CD4+ cells into Th17 cells in the later development of the child’s organism, which confirms the importance of the foetal period for the progression of depressive disorders.

Introduction

Depressive disorders are regarded as some of the main causes of disability globally. The World Health Organization (WHO) estimates that 350 million people around the world demonstrate symptoms of depression – they represent nearly 4.3% of the global burden of all diseases [1]. The risk of developing major depression during the entire lifetime is estimated at 8–12% [2]. The manifestation of symptoms is closely related to the risk of deterioration in patients’ functioning, increased disability, reduced quality of life and a negative impact on coexisting somatic diseases [3,4]. Depression limits the ability to work and is linked with an increased risk of premature death. The risk of suicide is substantially increased amongst the depressed population [5].

Therefore, depressive disorders represent an important personal, medical, social and economic problem. Besides the suffering of the affected person, depression has an adverse effect on the patient’s family relationships. The disease weakens the ability to perform everyday activities and affects relations with children. Hence the interest in the aetiology of depression and looking for new operative mechanistic aspects has stimulated the search for treatment options involving these particular elements. The inflammatory process present in depression has been studied for a number of decades and it is now clear that the immune system has a significant influence on the genesis and course of the disease [6]. Therefore, inflammation seems to be an area where potential new options of treating depression, especially drug-resistant depression, can be sought.

This article provides a review of available literature, which focuses on the neurodevelopmental nature of depressive disorders. In our opinion, effective functioning of the immune system is important. It is a system that coordinates the development of other systems, especially the nervous system, and in many aspects is convergent in terms of possible modifications and developmental periods. The publication focuses on showing this relationship through the description of co-development as the key to the development of immune system mobilization for pro-inflammatory preparedness. It presents the impact of stress and cytotoxic factors on immune activation – transformation of CD4 cells into various phenotypes leading to neuroprotective and neurotoxic effects. Research on the phenomenon of intergenerational transmission confirms the possibility of epigenetic inheritance of trauma, which in our opinion is related to the functioning of the immune system. In the summary of the publication we present proposals for treatment in drug-resistant depression accompanied by pro-inflammatory mobilization through the introduction of biological drugs that could potentialize the treatment process.