Major Depressive Disorder is a primary type and the most dominant type of depression. If you suffer from MDD, it is possible that other members of your family have the disease too. The reason is that the predisposition to have the disease is programmed in the genes. It is a familial disease—that is, it runs in the family. If you are predisposed to have the disease and at the same time are exposed to severe stresses of life, such as financial woes, marital and work-related problems, then very likely you will suffer from it.

Main Causes of Depression

Role of genes and serotonin
The cells in your brain are called neurons and they communicate to each other through chemical substances medically known as neurotransmitters, which move and travel in between them. One of these neurotransmitters is serotonin, which serves as the pivotal substance to which all the manifestations of MDD are attributed to. It was initially thought that when your serotonin level was low that you manifest MDD. However, in some instances, that observation did not happen. It took place only when the individual concerned happened to have a positive family history of MDD. In another saying, it is not enough that your serotonin level needs to be low so that MDD could take place. In addition, you must have the predisposition or genetic make-up to experience it. Thus, genes and serotonin level are probably involved in causing MDD, showing at a certain point that multiple factors are involved.

Your genes could predispose you to manifest MDD in several ways. Genes could influence the production and destruction of neurotransmitters and their receptors. Hence, they could increase or decrease the level of your serotonin. Receptors, on the other hand, are structures of your neurons which receive the serotonin; they serve as the landing pad of your serotonin molecules which will, in turn, act on other structures. Without the receptors, the serotonin has nothing to land on and it can’t do its functions. The genes could also influence the nature and competence of these receptors.

Your genes could also determine the type of your neurons and the type of their connections to other neurons, which, in turn, could affect the speed of neuronal signals traveling in and in between your neurons. This neuronal speed needs to be at par with what is normal so that you could respond properly to environmental stressors, such as pressure from work and from family affairs. If the speed is not within the required range, you could manifest MDD upon exposure to an environmental stress.

Your genes could also determine the type of your neurons and the type of their connections to other neurons, which, in turn, could affect the speed of neuronal signals traveling in and in between your neurons. This neuronal speed needs to be at par with what is normal so that you could respond properly to environmental stressors, such as pressure from work and from family affairs. If the speed is not within the required range, you could manifest MDD upon exposure to an environmental stress.

Specifically, the neuronal speed is primarily handled by the so-called serotonin transporter, whose nature is determined and influenced by the nature of your genes. Depending on the nature of your genes, the production and synthesis of your serotonin transporter could be slowed down. If the said transporter is low in number, even if your serotonin level is high, you could not immediately react to a stressor because your serotonin has nothing to ride on. Consequently, it cannot reach its destination.

Role of norepinephrine
There is a particular set of MDD symptoms called the positive effect. Clinical symptoms belonging to this group are a loss of pleasure, loss of interest, fatigue, and loss of energy. It was observed that this set of symptoms improves if the level of norepinephrine in your brain is normal. When it is reduced, the symptoms of positive affect manifest or start to come out. Thus there is an indication that norepinephrine is another neurotransmitter which is involved in the causation of MDD.

The proposition that norepinephrine affects another set of symptoms in MDD was bolstered when it was observed that the drug used for increasing the level of serotonin, otherwise known as the selective serotonin reuptake inhibitor, does not improve the symptoms of positive affect, whereas a drug which is known to increase the level of norepinephrine improves the said set of symptoms.

Role of dopamine
The third neurotransmitter that could be involved in the causation of MDD is dopamine. Results of scientific research tend to show that diminished dopaminergic neurotransmission could cause MDD. This reduction in transmission could be due to either diminished release of dopamine from the presynaptic neuron or there is impairment in the intracellular transduction of signals. In some occasions, where dopamine-related disturbances are involved, giving antidepressants may relieve your symptoms. However, in others, there are still symptoms that remain and persist. That is, not all of your symptoms could be alleviated by the drugs. This means that the present drugs being used in clinical practice do not directly enhance the dopamine transmission, thus failing to relieve some of your symptoms of MDD, such as impaired motivation, concentration, and pleasure. In some studies, including some post-mortem investigations, it was found out that the levels of dopamine metabolites in both the cerebrospinal fluid and the brain regions that mediate mood were low, indicating that indeed dopamine plays a great role in modulating your mood.

Other factors that could very likely trigger you to have MDD are hormonal imbalance, alcohol or drug abuse, medical conditions like cancer and hypothyroidism, and medications like steroids.