The Neurobiology of Depression, by Tamsin Embleton

There is still much to discover about the neurobiology of depression, but thanks to advancements in neuroscience, we now know that depression involves various brain regions, circuits, systems, processes, and neurochemicals.Brain scans revealed changes to the volume size and activity of several brain structures (in depressed brains when compared to non-depressed people), including those involved in detecting and responding to threat, learning and memory, sexual arousal, consciousness, emotional regulation. 

Differences in the cortical structures of depressed brains.

Brain AreaRole Change
HippocampusLearning and memory, behavioural and emotional responses, sexual arousal, and your sense of smell.Decreased volume One study found that found women who were depressed had between 9-13% reduction in grey matter in the hippocampus compared to women who were not depressed. 
Bilateral Caudate NucleusThis area helps you control bodily movement. It gets you motivated, helps you manage emotions and romantic interaction, and the systems involved in reward, learning and memory. Decreased volume A reduced volume in this area may correspond to the inhibited movement often seen in depressed people.
The ThalamusRegulates consciousness, and alertness. It also relays signals from the senses and the bodyDecreased volume
AmygdalaThreat response, defining and regulating emotions, judging safety/danger, attachment, early memory, emotional experience and implicit memory. The amygdala responds very quickly, meaning that your body can respond to a perceived threat before you’ve had a chance to evaluate whether a situation is truly threatening. 
Damage to the amygdala can result in impaired decision making, memory loss, and hypervigilance.
Decreased volume and increased activity. Depressed brains are thought to be more reactive to stress and fear, because of increased activity in the amygdala. When the amygdala is hyperactive, it can lead to aggression, violence, fear and anxiety (all of which can be symptoms of depression).
When the amygdala is underactive (or when activity is dampened down by alcohol or medication), you feel mellow. 
Anterior Cingulate CortexEmpathy, emotion, impulsive control and decision makingDecreased volume
Pituitary glandRegulates growth, blood pressure and is involved in reproductionLarger volume

Neurochemicals and depression

One of the first neurochemicals to discuss in relation to depression is neurotransmitter called serotonin. Serotonin helps you regulate your moods, helps you think clearly and is involved with reward, learning, memory, managing sleep-wake cycles, and digestion. Some studies found that less serotonin was available in the brains of depressed people (1). Researchers also discovered that changes to the genes that transport serotonin makes you much more vulnerable to the impact of early life stress (2) (which then increases the likelihood of depression developing in later life).

One widely used class of antidepressant medication is selective serotonin reuptake inhibitors (SSRIs), and selective serotonin-norepinephrine reuptake inhibitors (SNRIs). SSRIs and SNRIs increase serotonin availability, though it takes several weeks and it doesn’t work for everybody. 

Dopamine is a neurotransmitter involved in many body and brain functions like learning, motivation, sleeping, attention, pain management, heart, kidney and blood function, lactation, movement, and mood management. It also influences how you experience pleasure. Too much or too little dopamine can have serious consequences (3). It now seems that depression may involve a reduction in dopamine transmission and availability causing low motivation and rewarding feelings, low mood, difficulty concentrating, and a lack of desire (4). This might help to explain why for some people antidepressants that focus on serotonin uptake don’t have the desired effects. You can learn more about medication for Depression later on in this chapter.

Before we look further into clinical depression and treatment options, let’s take a look at who is most at risk, and how depression develops.


  1. This was due to a reduction in the activity of serotoninergic neurons, and a reduction in serotonin binding sites that make serotonin available.
  2. You can read more about adverse experiences in Chapter 3. 
  3. For example, people who are schizophrenic have excessive levels of dopamine in particular areas of the brain which causes hallucinations and delusions. Those who have Parkinson’s disease have too little dopamine (due to a degenerative neuron interfering with dopamine production), which causes physical symptoms like poor balance, tremors, stiffness, poor coordination, and slower movement.
  4. Sadeaunu, R.V. & Nemeroff, C.B., 2012. Etiology of Depression: Genetic and Environmental Factors. Psychiatric Clinics. Available at: [Accessed September 28, 2021].