Despite the fact that the factors associated with major depressive disorder (MDD) and neurobiological processes that cause this pathology have been studied in detail, there is still a component of this disorder that remains hidden and serves as a subject of interest to specialists.
This component is associated with genetics and changes in molecules; studies conducted in the field of neurobiology and, in particular, psychiatric diseases, were usually aimed at finding possible genetic sources that are responsible for the development and course of major depressive disorder.
In this article, we will shed some light on the genetic aspects of the origin and development of MDD, as well as on new ways of research, both by methods and in the field of biology, which are currently being conducted, and can help us understand this disease.
Etiology of Major Depressive Disorder
Although the main cause of major depressive disorder has not been clarified one hundred percent, experts consider it a combination of three factors: genetic, physiological and psychosocial.
Regarding genetic causes, various studies agree that there is a link between heredity and depression in the genesis of depressive episodes. The number of emotional disorders in relatives of patients is much higher than in healthy people, which is especially pronounced for severe disorders.
So, if someone suffers from severe depression, the probability that their child or sibling will also get this disease is 25%. The percentage probability increases significantly in the case of homozygous twins, including cases when they were separated at birth.
Depression can also be caused by physiological reasons. It has been established that major depressive disorder originates with an imbalance of certain brain substances, including serotonin, dopamine and norepinephrine.
Some external circumstances that potentially served as a stress factor can also be considered factors of provoking depressive states. These psychosocial reasons usually reflected the whole set of situations causing this disorder.
Neurochemical Basis of Depression
Various hypotheses have been proposed regarding the biochemical and neurophysiological basis for major depressive disorder, although there is still insufficient research in this area. Of all the hypotheses, scientists are most inclined to the monoamine energy hypothesis.
According to this hypothesis, the causes of depressive symptoms are changes in the levels of neurotransmitters. To be precise, it has been established that an imbalance occurs between three monoamines – serotonin, dopamine and norepinephrine.
First, it is necessary to understand that neurotransmitters are biomolecules that provide information transfer between neurons through synapses. It is from them that neurotransmitters are released, filling the synaptic space and reaching the membrane of a neighboring neuron.
Currently, more than 50 substances are known to act as neurotransmitters. Of these, the three mentioned above, according to the monoamine energy hypothesis, are probably responsible for depression in humans.
Genetic Component of Depressive Disorder
By analogy with most pathologies affecting us all, major depressive disorder belongs to a group of diseases defined as genetically complex.
Moreover, both environmental and genetic factors play a decisive role in the origin of this disease. In this regard, various studies conducted in recent years have been aimed at establishing the genetic component of depression.
Transmission of this disease is usually explained by the threshold of susceptibility model, according to which it is assumed that a variable coefficient of susceptibility for the development of pathology is distributed among the population with a constant level, so only some people who have crossed this threshold show a disorder.
Family studies show the first approximation of hereditary components that are taken into account in depression. Such studies make it possible to calculate the risk of illness in family members; for example, the tendency to depression is higher in relatives of people suffering from the disease than in the general population.
In turn, the adoption studies have given rates of depression incidence much higher than expected for the general population. These studies were based on children at high risk of MDD who were brought up in families that did not have ancestors with depression. The results were a demonstration of the genetic risk factors for the MDD disease.
At the same time, studies on twins did not allow to accurately and convincingly establish the components associated with hereditary issues, and some of them showed contradictory results or low values of heredity.
Other studies were conducted to study the genetics of mental illnesses, such as link analysis; still, in the absence of a model of heredity according to Mendel’s laws for such diseases, the results were more or less insufficient.
In 2018, the genetic link analysis was conducted (Wray et al., 2018), based on the study of 135,458 cases and 344,901 controls, in which 44 regions of the genome associated with depression were detected, which helped to clarify our knowledge about the biological and genetic basis of this disease. Along with the other two large communication studies, 80 regions of our genome have been described and replicated that may contribute to the development of depression.
Factors related to MDD
Major depressive disorder is the fourth cause of disability worldwide, and despite manifestations also in children and adolescents, usually the majority of those suffering from depression are 30 years of age and older.
Among the factors associated with the development of this disease, there are anxiety disorders, low self-esteem, external events of a stressful nature and emotional instability, as well as others.
Scientific achievements in the field of genetics, epigenetics and neurobiology have made it possible to understand that many physiological changes present in major depressive disorder contain an important hereditary component. Still, additional and more in-depth studies are required, which will help to determine the hereditary factor of the disease most clearly.
