Mood disorders

“One swallow does not make a summer, neither does one fine day; similarly one day or brief time of happiness does not make a person entirely happy” Aristotle

Important note: the purpose of the following article is to introduce and explain some concepts related to depression. It should NOT be treated as a diagnosis nor a treatment plan. In case you think you might be affected by depression, immediately contact your doctor!

Image credit: Ewa Klejman

Mood disorders, which are classified as a mental illness called depression, have now become the leading disease of civilization. There are as many reasons for depression as there are people who suffer from it. It is usually associated with feelings of sadness, loss, or anger that interfere with daily activities. Despite the frequency with which it occurs, depression remains a disease shrouded in many mysteries and is often difficult to diagnose. Here, we will try to explain this mental condition by exploring the chemistry inside our brain, which causes it.

What is depression? How to diagnose it?

Probably, due to the COVID-19 pandemic, lockdowns, social distance, and stress, the most common mental problem is depression [1]. What is this mental state? The word depression is very commonly associated with sadness, feeling horrible, and devastated, but this disease is much more complicated than many think. There are not relatively non-specific symptoms of depression, making it common to remain undiagnosed and untreated. What factors are responsible for making some people more prone to depression and others the opposite? You may find it strange, but they can contribute to its development, such as factors like chronic stress or various life situations, the appearance of which impacts the endocrine system, which produces hormones (substances that regulate different processes in our body), see Figure 1. They belong to such life situations as family history and early childhood trauma. Even a slight disturbance of the latter causes the organism to be unbalanced for a very long time. It may seem impossible, but many people have genetic predispositions to develop depression [2, 3].

Figure 1. The reasons behind depression. Image credit: Ewa Klejman

Depression can have many symptoms. Unfortunately,  we can still distinguish the most common ones, including sleep disturbance, lack of appetite, decreased sense of pleasure, loss of interest in other people and surroundings, or even more severe symptoms like psychomotor disturbance, depressed mood, or even suicidal thoughts [4]. It is often taboo, but depression requires professional medical treatment and diagnosis, just like any other disease. However, let us remember that each case is different, and there is no simple solution to this problem. To find a solution to them, we must look deep into the human soul and brain.

How does the brain signal depression to us?

Figure 2. The structure of the nervous cells (neuron), and the communication between two neurons (synapses). Image credit: Ewa Klejman

The human brain is made up of nerve cells, so called neurons. They are connected in a colossal network containing many connections, so-called synapses, see Figure 2. Each synapse communicates with the other by releasing tiny information-carrying particles (neurotransmitters) due to an electrical impulse. When depression occurs, it is a sign that this communication is failing [5].

In order to understand depression, we have to talk a bit about the type of neurotransmitters and how they affect our brain. The three most common neurotransmitters are associated with depression: dopamine, serotonin, and norepinephrine [6].

The first one, dopamine, is responsible for pleasure, memory, and, most importantly, part of the reward system. Once we do something, our brain considers a completed task, it releases dopamine, and we feel good. Therefore our motivation to continue doing things is increased. We get a reward in a way. When dopamine is depleted, our brain is deprived of sources of happiness and motivation, thus resulting in the symptoms related to the reduction of feeling of pleasure and lack of motivation [7].

The task of the second neurotransmitter – serotonin, is to stabilize your mood, induce feelings of satisfaction, and help with sleeping and eating processes. Lack of serotonin results in various sleeping and eating disorders; since it is one of the substances responsible for maintaining balance within our body. Its decrease also causes anxiety and impulsive behaviors [8].

The last one, norepinephrine (also called noradrenaline), acts as the focus and stress neurotransmitter. It plays an essential part in memory and stress processes, regulates emotions and energy levels. A decreased amount of norepinephrine causes memory problems, loss of concentration, and lack of motivation [9].

Believe it or not, but a long-term deficiency of these neurotransmitters causes depression. There are many types of depression, and there is a slightly different reason behind each of them. Let’s talk about the most common ones. Here, we will focus on the most common ones.

The wealth of the world of depression

Sadness is an integral part of human existence. Normally, this feeling is short-lived, but it can sometimes turn into a serious depressive disorder. An example is Major Depressive Disorder (MDD) also called clinical depression has a long list of symptoms, including loss of interest, depressive mood, and some physiological ones such as sleeping problems, loss of appetite, and lack of energy. Additionally, it can involve suicidal thoughts, which may lead to suicide [10]. Let’s consider in which part of our brain it arises. The three main structures:  hippocampus, prefrontal cortex, and amygdala play an important role in the development of this disease, see Figure 3.

The role of the hippocampus besides cognition, memory, and navigation is regulating the production of stress hormone – cortisol. You have probably heard that long-lasting stress is unhealthy at least once in your life, but have you ever wondered why? The answer is very simple. When we are exposed to stress for too long, we are constantly affected by high doses of cortisol. The neuron production slows down and the neurons located in the hippocampus start to shrink. The same thing happens to the prefrontal cortex. Prefrontal cortex is a structure  responsible for emotion regulation and decision making.

The last part, the amygdala, is responsible for generating the response to certain emotions. People affected by MDD have larger and more active amygdala. This can lead to increased release of hormones, which later affects our mood and the way we feel [11-15].

Figure 3. The placement of the hippocampus, prefrontal cortex, and amygdala in the human brain. Image credit: Ewa Klejman

Another form of depression is Persistent depressive disorder (PDD) also called dysthymia. It is a continuous and long-lasting form of depression.  It has similar symptoms as MDD. However, these feelings last for years and can significantly affect life and relationships with other people. Because of its long duration, people experiencing it may often refer to their disease as being “part of them” [16].

Depressive states can be related to the seasons and their changes. For example, Seasonal Affective Disorder (SAD) occurs during the fall-winter period. It happens because days become shorter, and the natural body rhythm is disturbed. The serotonin and melatonin release is changed. Lack of light results in producing too much melatonin (sleep hormone) and decreasing the production of serotonin. Thus, melatonin fluctuations are common in various types of depression. Serotonin deficiency causes depression symptoms to occur. The symptoms of SAD are similar to those present in MDD [17].

An extreme case of depression is  Bipolar Disorder (BD), formerly called manic depression. People who suffer from it experience episodes of mania and depression. As you probably know, the mania episode is the opposite of a depressive episode. People become hyperactive, have high self-esteem, and unrealistic ideas. The symptoms during depression episodes are very similar to those in MDD. Despite having similar depression symptoms, how different is the chemistry behind BD than in MDD?

The cause of Bipolar Disorder remains a mystery. However, there are a few concepts discussing it. The first one is related to the chemical imbalance in the brain. It states that BD is a result of improper work of neurotransmitters such as serotonin, dopamine, and noradrenaline. The second theory is related to genetics, and it states that the tendency to fall ill is higher in the families that already have a person affected by BD. The last one suggests that people may have bipolar disorder due to environmental factors. However, BD can also be triggered by the combination of all of these factors [18-19].

Summary

Depression is a complex disease, and each person has a different course of it. Sometimes it is easy to treat, and sometimes it is not. The list of reasons causing depression is as long as the list of its symptoms. Inadequate levels of neurotransmitters like dopamine, serotonin, and norepinephrine causes depression, while the neurons cannot regulate the electrical impulse efficiently, preventing appropriate transmission of information. In treating depression, as with any illness, the most important thing is to contact your doctor, in this case, a psychiatrist or psychologist.

This article is a joint work of Ewa Klejman (Faculty of Chemistry, University of Warsaw), and Agnieszka Pregowska (Institute of Fundamental Technological Research, Polish Academy of Sciences) as a part of the Science Embassy project. Image Credit: Ewa Klejman.