Biology of depression: What is happening in the brain of a depressed person…
A literal ton of research has been done to show that numerous brain areas show altered activities in depressed patients. This led to the origin of biochemical origin of the disease, as opposed to its psychological or situational origin.
A number of chemicals and neuorchemicals are involved, working both inside and outside the nerve cells and it is a result of these chemical reactions happening constantly that depression creeps in.
1. Brain regions.
Science has tracked the seat of depression to the brain. Many areas in the brain regulates mood. Nerve cell connections, nerve cell growth and functioning of nerve circuits are seem to be altered in depression.
The brain areas that are affected in depression are the amygdala, the thalamus, and the hippocampus
Research shows that the hippocampus (part of limbic system responsible for processing long term memory) is smaller in some depressed people. In one study of 24 depressed women published in The Journal of Neuroscience, investigators found that the hippocampus was 9% to 13% smaller as compared to the age matched controls. The more severe depression a woman had, the smaller the hippocampus was.
Stress, that is supposed to play a critical role in depression, may be a responsible factor here, since experts believe stress can suppress the synthesis of new neurons (nerve cells) in the hippocampus.
The possible connection between reduced production of new neurons in the hippocampus and low moods are supported by the role of antidepressants.
As these medications immediately boost the amount of neurotransmitters in the brain but still people don’t begin to feel better for several weeks or longer.
This is because the mood only improves as the nerves grow and form new connections-this process takes several weeks. This is supported by animal studies that have shown that antidepressants stimulate the branching of nerve cells (neurogenesis), strengthens nerve cell connections, and improve the exchange of information between nerve circuits in the hippocampus.
- Amygdala The amygdala is also a part of the limbic system (area that governs emotions).The amygdala is activated when a person recalls emotionally stimulating memories or intrusive memories. The activity of amygdala is seems to be elevated in depressed patients.
- Thalamus The thalamus is the area of the brain that receives maximum amount of sensory information and it relays it to the appropriate higher brain area. It is involved in behavior, movement, thinking and learning. Some research suggests that depression may result from problems in the thalamus, which helps in linking sensory input to pleasant and unpleasant feelings.
Neurotransmitters are chemical messengers responsible for communication between the nerve cells. Most antidepressants increase the concentration of these chemicals in the spaces (the synapse) between two nerve cells
Brain cells usually produce a certain levels of neurotransmitters that keep senses, learning, thinking, movements, and moods working efficiently. But in some depressed or manic people this complex system goes awry, which can significantly affect mood.
Kinds of neurotransmitters: What follows is the description of neurotransmitters that are believed to play a role in depression:
- Acetylcholine: enhances memory, learning, decision making and recall.
- Serotonin: regulate circadian rhythm and mood and inhibits pain. Lack of serotonin leads to anxiety, obsessions and compulsions. Some depressed people have reduced serotonin levels.
- Norepinephrine: raises blood pressure, determine arousal, energy and reward. It can trigger anxiety and is involved in some types of depression
- Dopamine: influences motivation, interest in life and plays a role in how a person perceives reality. Alteration in dopamine transmission have been linked with psychosis- hallucinations or delusions
- Glutamate: an excitatory neurotransmitter, lack of which is seen in bipolar disorder and schizophrenia.
- Gamma-aminobutyric acid: (GABA) is an amino acid that acts as an inhibitory neurotransmitter, which helps to quell anxiety.
Genes make proteins that control every biological process. But if the genes make wrong protein at the wrong time, they can alter your biology in a way that results in altered mood processing. In a genetically vulnerable person, even a trivial form of stress can push this system off balance.
In 2003, Researchers found that people having a particular variant in a serotonin-transporter gene (5-HTT) were more likely to become depressed. All of us inherits two copies of this gene — one from each parent. The gene comes in “short” i.e. less efficient and “long” i.e. more efficient variant. Combination of short or long versions cannot directly lead to depression. But people getting small version are more vulnerable to depression if they experience stressful life events.
In a study of about 800 young adults conducted for a five-year period, the researchers found that 33% of those with at least one “short” gene became depressed after a series of stressful life events. Whereas, only 17% of those with two “longs” genes developed depression in similar circumstances
In 2008 study published in archives of general psychiatry, researchers studied a protective version of gene CRHR1. In this study, researchers tested DNA of 621 adults who suffered childhood abuse. They found that people having protective version of this gene were having half the symptoms of depression than people without this gene.
Another interesting discovery is the identification of another DNA variant named- G1463A. People having this atypical DNA sequence are more vulnerable to depression than those who don’t.
Perhaps the easiest way to know the influence of genes is to look at families. A person who has a first-degree relative suffering from depression has a in risk of about 1.5% to 3% for developing depression.
Studies have documented the role of altered neuroplasticity in the incidence of depression. A review published in Neuropsychopharmacology (2008) found chronic stress can alter neuroplasticity by convergence of three phenomenons:
- Chronic stress can substantially reduce number of dendrtitic spines ( projection of a nerve cell that is helpful in information transmission, memory storage, motivation and learning).
- Chronic stress can also reduce the length and complexity of cortical dendrites ( implicated in memory ,learning and modulation of sensory associations).
- Chronic stress has been seen to impair neurogenesis.
Studies have shown that many molecular mechanisms of neuroplasticity are induced by anti-depressants-that includes-synaptic plasticity ( changes in dendritic spines in many brain areas, most prominently in hippocampus), increase in level and complexity of dendritic lengths and neurogenesis.
5. Hormones and Endocrine System.
Hormones are the chemical messengers that are produced by endocrine system. The endocrine system is under the control of hypothalamus (switching station of the brain)- that controls circadian, seasonal rhythms, appetite, behavior, temperature, immune functions and blood pressure.
Circadian rhythm or 24-hour body cycle is mainly controlled by hypothalamus, which does so, by determining the amount of light in a day-night cycle. Both brain activity and hormone production are dependent on this rhythm. Altered circadian rhythm can lead to mood disturbances.
Similarly seasonal rhythms are determined by amount of light in a particular season and its alteration is seen in seasonal affective disorder (SAD)
The hypothalamus is also responsible for the production of stress hormones. Numerous studies have documented a positive correlation between increase levels of stress hormones and depression
Other than hypothalamus, endocrine organs such as the thyroid, adrenal glands, ovaries and testes have also been linked with depression.
Low levels of thyroid hormones, produced by thyroid gland in neck, can lead to depressive symptoms. The adrenal glands, located near the kidneys, produce cortisol that controls metabolism, immune function, and the stress response. Over-activity of adrenal glands is usually seen in depressed individuals.
Reduced level of Estrogen produced by ovaries can alter activity of neurotransmitters- serotonin and norepinephrine and can lead to depression. This explains why women are more prone to depression than men.
Testosterone, produced by the testes in males, is also linked to depression. Studies have suggested a decrease in its level after the age of 50. This might be one of the reasons why men after 50 become more susceptible to develop depression.
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