Understanding the level of Serotonin and Dopamine in a depressed person’s brain

Let us look at the state and level of two neurochemicals called serotonin and dopamine in a depressed person’s brain.

A small background and context:

• Neurotransmitters/Neurochemicals are chemicals that allow neurons (brain cells) to communicate with each other.
• Some cells use specific neurotransmitters/neurochemicals for communication.
• There are over 60 neurotransmitters^[1] across the whole brain in various regions.
• Serotonin and Dopamine are 2 famous neurotransmitters. Medication for depression addresses the ‘level’ of these neurotransmitters.

We are here to understand what dopamine/serotonin levels mean. Because there is a lot of awareness, people talk about levels as it is the easiest (albeit misleading) way to conceptualize it. What does it mean to have low dopamine or high serotonin in the brain?

Is depression caused by low serotonin or dopamine?

This question is a common one and it isn’t very useful. I’ll explain why.

The reason I want to discuss the role of serotonin and dopamine in depression and not the cause is that depression is complex, the brain and mind is complex, and us being alive in an environment complicates things even more. To the point that determining a cause is extremely hard – hundreds of factors that include trauma, neurochemicals, lifestyle, genetics, etc. affect each other. Some combination of the specifics in these factors is associated with depression.

Let’s return to dopamine and serotonin. Before I write about dopamine and serotonin levels in depression, I’d like to lay down a foundation. People use the word level. But what does dopamine level actually mean with respect to neurons?

What is the ‘level’ of serotonin and dopamine?

1. The brain isn’t a chemical soup where neurons and neurochemicals flow like blood.
2. When we speak of the level of a neurochemical/neurotransmitter, there are different aspects of ‘level’ to consider. I’ll leave out the actual electrical aspects of the neural signal because that’ll lead to digression.
   1. Reuptake – When a neuron sends a signal from one cell to the other, a neurotransmitter is involved. A neuron has a synapse which acts as the communication portal. A neurotransmitter, which is present inside vesicles just before the synapse, causes the communication. In that process, the neurotransmitter (NT) will be reabsorbed by the synapse and thus change its availability in the synapse. This is one type of level. Medicines such as SSRIs (selective serotonin reuptake inhibitors) inhibit the re-uptake. This affects the ‘level’ of the NT.
   2. Metabolism – Now NTs are created inside the cell body and transported to the synapse. Sometimes the metabolism can be unfavorable and not enough is synthesized for proper functioning. So, the level of the NT is affected at its supply.

We’ve now looked at 2 important aspects of the level of neurotransmitters in the brain – availability and supply. I’d like to stay away from the word deficiency because it doesn’t account for the mechanisms involved in the apparent amount of NT there is for functioning. The mechanism is important.

Now let us move to serotonin and dopamine in depressed people.

Serotonin and depression

A large body of evidence coming from humans and mouse models of depression show that serotonin’s metabolite is reduced. That means its production is hampered. This is where SSRIs are helpful because reuptake of serotonin is inhibited and the apparent availability in the synapse is increased in spite of a poor supply of it (production).

Dopamine and depression

Dopamine is unfortunately infamous. What we know is that dopamine is involved in all sorts of functioning in healthy and depressed patients. There is evidence that homovanillic acid, a dopamine metabolite, leads to poor production of dopamine for neural pathways that release dopamine at the synapse. Medication that promotes dopaminergic activity in the brain has antidepressant effects. But because dopamine is associated with attention, stimulation, reward perception, surprise, etc. (basically everything) it is hard to call it a cause.

Understanding the interaction of behaviors and neurotransmitters

The thing is, neurotransmitters work within their means at their usual neural pathways but they work in tandem with the brain, behavior, and thought. Neurochemicals, behavior, and thoughts are in positive and negative feedback loops.

A particular behavior may cause a change in the apparent level of the NT, or a change in a particular NT will make a particular behavior or tendency more likely. It is hard to understand what happens first.

A reduction in activity of neurons which use dopamine or serotonin for communication can affect the behavior of a depressed person (or any person). The opposite is true as well. Learning new behaviors can affect the activity of those neural networks too.

When it comes to treatment, the important point is that one affects the other – Behavior/thought AND the neurotransmitter. If you are interested in how learning affects neurons, you might find this short post interesting.

Can one say that depression is caused by deficiency of serotonin or dopamine?

Maybe in a simplistic world, that would be correct. But the truth is complex. We do know that their level is lesser with respect to supply or synaptic availability. That is why re-uptake inhibitors can change the apparent level. This is a more useful way of saying the same thing – depression is associated with both a deficiency of serotonin and dopamine.

Sources:
Dopamine and depression^[3]

Involvement of Serotonin and Dopamine in the Mechanism of… : Journal of Clinical Psychopharmacology^[4]

A New Strategy for Antidepressant Prescription^[5]

Sources