The main subcortical limbic brain regions implicated in depression are the amygdala, hippocampus, and the dorsomedial thalamus. Both structural and functional abnormalities in these areas have been found in depression.
Research by the National Institutes of Health shows that you lose gray matter volume (GMV) when you suffer from depression. This loss is caused by parts of your brain shrinking due to the hormone cortisol impeding the growth of your brain cells. The more serious depression a person suffers, the more GMV they lose.
Changes in brain chemistry, especially disruptions in neurotransmitters like serotonin, that play an important role in regulating many bodily functions, including mood, sleep, and appetite, are thought to play a particularly important role in depression.
The brain's limbic system, comprised of the hippocampus, amygdala, hypothalamus and thalamus, is responsible for the majority of emotional processing. Individuals with an anxiety disorder may have heightened activity in these areas.
With regard to depression, neuroimaging studies in humans show that in response to viewing sad faces, the amygdala of depressed people is extremely active when compared to the amygdala of non-depressed people, yet when viewing happy faces, amygdala activity is not distinguishable between the two groups.
Volume reduction of the prefrontal cortex may result from the disruption and atrophy of neurons and glia in depression, as observed in the hippocampus [21, 22]. Energy and glutathione metabolic pathways in the prefrontal cortex were shown to be significant biological pathways in depressive rats [58].
The study, which gathered evidence from 361 peer-reviewed scientific studies, found no link between depression and serotonin levels in the blood.
A PET scan can compare brain activity during periods of depression (left) with normal brain activity (right).
Since the frontal lobe governs memory, emotion, judgment, executive functions, and behavior, a lesion of this lobe is the most common cause of depression or other mood disorders [12]. A lesion of the dominant frontal lobe is more likely to cause these disorders.
The majority of changes and damage to the brain caused by untreated depression are not believed to be permanent, but more research is still needed. When depression is effectively treated, most people commonly experience an improvement in symptoms, and their brains return to typical function and structure.
While it is true that low levels of neurotransmitters like serotonin or norepinephrine can play a role in depression for some people, this is only one piece of a much larger puzzle. In fact, the chemical imbalance theory has not been proven as the main cause of depression in over 50 years of research.
Recent studies suggest that the increased level of stress associated with depression may raise levels of glucocorticoid. This steroid can have harmful effects on the nervous system, damaging a region of the brain called the hippocampus that is crucial to creating long-term memories.
There's no single cause of depression. It can occur for a variety of reasons and it has many different triggers. For some people, an upsetting or stressful life event, such as bereavement, divorce, illness, redundancy and job or money worries, can be the cause. Different causes can often combine to trigger depression.
When comparing a depressed brain versus a normal brain, scientists have found some subtle but important differences including grey matter abnormalities, brain shrinkage, and a more active amygdala in depressed brains.
The monoamine-deficiency theory posits that the underlying pathophysiological basis of depression is a depletion of the neurotransmitters serotonin, norepinephrine or dopamine in the central nervous system. Serotonin is the most extensively studied neurotransmitter in depression.
Loss of volume of the part of the Brain
Results of several MRI scan studies have demonstrated people with depression had a hippocampus volume that was up to 10% lower than people without depression.
Damage to the amygdala can cause a variety of symptoms, most often emotional and behavioral. Individuals may experience irritability, confusion, and a variety of strong emotions. Symptoms of amygdala damage can be complex and may require a combination of treatments.
Acquired amygdala damage reliably impairs fear conditioning, and behavioural, physiological and (in humans and perhaps other species, subjective) responses to threats [6–9].
However, researchers believe that an imbalance of these neurotransmitters is a major factor in the development of depression. A dopamine imbalance can cause depression symptoms, such as apathy and feelings of hopelessness, while a serotonin imbalance can affect the processing of emotions.
Certain drugs and substances such as caffeine, alcohol, nicotine, NutraSweet, antidepressants, and some cholesterol-lowering medications deplete serotonin and other neurotransmitter levels.
Low dopamine levels are linked with certain health conditions like Parkinson's disease or depression. It may also make you more susceptible to taking risks or developing addictions.