The Chemistry Behind Depression

Researchers have expressed concerns that pharmaceutical companies marketing antidepressant medicine may have misled consumers by oversimplifying or misrepresenting the research into chemistry of depression.

An introduction to depression

Depression is a serious mood disorder affecting over 264 million people globally, often characterised by persistent symptoms of low self-esteem, sadness, loss of interest and hopelessness, affecting many daily lives. There are many different forms of depression, and the causes vary for each individual, making it both difficult to diagnose and treat. The level of complexity and number of chemicals that make up the dynamic system further contribute to the difficulty in treatment. Scientists have suggested that it is the functioning of nerve circuits, nerve cell growth and connections between the neurons in the brain have the paramount effect on depression, yet research and knowledge on the neurological causes of mood disorders is still largely incomplete. In this article I will explore the function and change in levels of neurotransmitters and the neurobiological theories that suggest to their supposed role in depression.

So, what are neurotransmitters?

Neurotransmitters are commonly named the ‘chemical messengers’ of the brain and are used by neurons to communicate across a synapse (the space between two nerve cells). They are produced, packaged and released from the axon of a presynaptic neuron (the neuron transmitting the signal) to a post synaptic cell. As this package of neurotransmitters cross the space between nerve cells, specific receptors on the postsynaptic cells (the neuron that receives the signal) take up these neurotransmitter bundle. For example, a neurotransmitter package of serotonin will be picked up by serotonin molecules. There are certain neurotransmitters that scientists believe to be linked to depression, these include dopamine, norepinephrine, and serotonin.

How do neurotransmitters play a role in depression?

Research suggests that low levels of neurotransmitters, especially those above, play a large role in depression. The neurotransmitter Dopamine creates a happy feeling that is associated with reward from a task, regulating our drive to seek reward and obtain pleasure. Low levels of this Norepinephrine acts as both a neurotransmitter and hormone. It contributes to the ‘fight or flight response’ alongside adrenaline and is believed to be one of the largest contributors to depression when in short supply. In the early 1950s physicians treated a group of patients suffering from hypertension with the drug reserpine and found that in 15% of these patients, severe depression arose, later finding that the drug turned out to deplete monoamines as it reduces the amount of norepinephrine released across the synapse. This treatment therefore suggests that depletion of norepinephrine can cause depression, and this theory is supported by scientist Joseph J. Schildkraut. Schildkraut presented his ‘catecholamine hypothesis of mood disorders’ which became popular in the 1960s, proposing that low levels of catecholamines (monoamine neurotransmitters), especially norepinephrine in certain nerve circuits, cause depression. Further autopsy studies supported this theory, by presenting that those who experienced major depressive disorder had less norepinephrinergic neurons than those who had not. However, depression medications targeting norepinephrine alleviated depression in some people but not others, and some people who are depressed in fact show hyperactivity within norepinephrinergic neurons, proving that catecholamines like norepinephrine cannot be isolated as the only chemical involved in the neurobiological theory of depression. Serotonin is another neurotransmitter, often labelled a ‘happy chemical’ that in low amounts supposedly contributes to causing depression, it controls mood as well as aiding with many other bodily functions such as sexual function and blood clotting. Arthur J. Prange and Jr. Alec Coppen’s hypothesis suggested low levels of this neurotransmitter caused triggered a drop in norepinephrinergic neuron activity, but that norepinephrine levels could be indirectly raised by manipulation of serotonin, and this theory leads the basis of many antidepressant medications. Although all these theories of depression linked to low neurotransmitter levels, scientists are still wary of an entirely sure and as simplistic connection as they don’t have a way to measure accurately and consistently specific neurotransmitters and brain chemicals.

What causes low levels of neurotransmitters?

Researchers are not sure about the cause of low serotonin levels and believe that biologically some may just have more than others. However, life events are believed to contribute to a depletion in neurotransmitters. A 2009 study by Jeffrey M. Miller discovered that those who had experienced abuse in childhood had a lower bind potential of the transporter for serotonin than those who had not experienced abuse, presenting that those who had been abused had reduced serotonin activity. Other experts believe stress can suppress the production of new neurons in the hippocampus, therefore decreasing neurotransmission. Hormonal shifts such as menopause, pregnancy or advancing age can also cause a decrease in serotonin levels. Psychological conditions such as OCD, eating disorders, PTSD, panic disorder and social anxiety are also believed to deplete neurotransmitters especially serotonin.

Medications and how they work to help with depression

Antidepressants immediately boost concentration of neurotransmitters in the brain, and animal studies have presented that antidepressants further increase the growth of branching of nerve cells, showing that the true value in these medications is not individually boosting concentration of neurotransmitters, but of stimulating neurogenesis (generating new neurons) and strengthening nerve cell connections. However, depression medications often take several weeks or longer to make those taking them feel better, so therefore experts questioned why, if the medications immediately boost neurotransmitter concentration, people don’t feel an improvement as soon as the neurotransmitter levels increase. However, some suggest it is the process of growing new nerves and connections between them that takes time therefore causing the delay in effectiveness of medication. Perhaps, depression medications could be specifically developed to promote neurogenesis and thereby give faster results. Yet, just as with the symptoms and causes of depression, one medication does not suit everybody, some even work well in some people but then become less effective and stop working entirely, for reasons scientists have still not discovered.

Although this neurotransmitter theory of depression is supported by much evidence, the connection is still not entirely sure, as scientists are far off providing fully concrete evidence and eliminating other possible theories. Other possible theories that researchers suggest could cause depression are of hormones, inherited traits from genetics and hormone changes.

Verywell Mind. 2021. What Is the Chemistry Behind Depression?. [online] Available at: [Accessed 4 July 2021].

M. Miller, J., 2009. Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder. [online] Available at: [Accessed 4 July 2021].

Harvard Health. 2019. What causes depression? - Harvard Health. [online] Available at: [Accessed 4 July 2021].

Schildkraut JJ. The catecholamine hypothesis of affective disorders: a review of supporting evidence. 1965. J Neuropsychiatry Clin Neurosci. 1995 Fall7(4):524-33 discussion 523-4. doi: 10.1176/jnp.7.4.524. PMID: 8555758.