Major depressive disorder is a mood disorder characterized by depressive symptoms that last
longer than 2 weeks. Though the exact cause is unknown, depression can be influenced by
genetic and environmental factors. Stressful life events, such as giving birth or experiencing
emotional trauma, can also impact the development of depression. Recent research has tied
depression to decreased activity of the prefrontal cortex. The prefrontal cortex controls attention,
memory, mood, and personality.
Symptoms of depression can include difficulty making decisions, feeling hopeless and sad, and
feeling guilt or self-negativity.
It takes 2 to 4 weeks for tricyclic antidepressants to reach a therapeutic blood level
Acetylcholine is involved in regulating neural circuits associated with mood and emotion,
particularly in brain regions such as the hippocampus and prefrontal cortex. Changes in
acetylcholine levels or receptor function in these areas may impact mood regulation and
contribute to depressive symptoms.
Acetylcholine's impact on muscle contraction is not related to its impact on mood. Acetylcholine
binds to postsynaptic (not presynaptic) neuron receptors. Acetylcholine acts on two main types
of receptors: muscarinic receptors and nicotinic receptors.
Serotonin
Synthesis and Release: Serotonin is synthesized in the neurons from the amino acid tryptophan.
Once synthesized, serotonin is stored in vesicles within the nerve terminals.
Release and Reuptake: When a nerve impulse reaches the end of a neuron, serotonin is released
into the synapse (the gap between neurons). After release, some of the serotonin binds to
receptors on the postsynaptic neuron, transmitting the signal. The remaining serotonin is taken
back up into the presynaptic neuron through a process called reuptake, where it can be recycled.
Receptors: Serotonin binds to specific receptors on the postsynaptic neuron. There are various
subtypes of serotonin receptors (e.g., 5-HT1, 5-HT2), and their activation can have different
effects on mood, emotion, and other physiological functions.
Norepinephrine
Synthesis and Release: Norepinephrine is synthesized from the amino acid tyrosine. Like
serotonin, it is stored in vesicles in the nerve terminals.
Release and Reuptake: Upon a nerve impulse, norepinephrine is released into the synapse. It
then binds to receptors on the postsynaptic neuron. The unbound norepinephrine is also subject
to reuptake into the presynaptic neuron for recycling.
,Receptors: Norepinephrine primarily acts on adrenergic receptors, of which there are alpha and
beta subtypes. The activation of these receptors can have various effects on mood, alertness, and
other physiological responses.
Dopamine
Dopamine is another important neurotransmitter in the brain, and it plays a crucial role in various
physiological processes, including mood regulation, motivation, reward, and motor control.
While dopamine is not as directly linked to depression as serotonin and norepinephrine, it still
plays a role in our understanding of mood disorders.
Synthesis and Release: Dopamine is synthesized from the amino acid tyrosine, and its
synthesis takes place within the neurons. Once synthesized, dopamine is stored in
vesicles in the nerve terminals.
Release and Reuptake: When a nerve impulse reaches the end of a neuron, dopamine is
released into the synapse. Dopamine binds to receptors on the postsynaptic neuron,
transmitting the signal. Unbound dopamine can be taken back up into the presynaptic
neuron through reuptake for recycling.
Receptors: Dopamine acts on several types of receptors, classified into D1-like
(including D1 and D5) and D2-like (including D2, D3, and D4) receptors. The activation
of these receptors can have different effects on mood, motivation, and other physiological
functions.
Acetylcholine
Acetylcholine is a neurotransmitter that plays a crucial role in various physiological
functions, including muscle contraction, memory, and the regulation of the autonomic
nervous system. While acetylcholine is not as prominently studied in the context of
depression as serotonin, norepinephrine, and dopamine, it does play a role in balancing the
other chemical messengers.
Synthesis and Release: Acetylcholine is synthesized in nerve terminals from choline and
acetyl coenzyme A. After synthesis, acetylcholine is stored in vesicles within the nerve
terminals.
Release and Reuptake: When a nerve impulse reaches the end of a cholinergic neuron,
acetylcholine is released into the synapse (also known as the cholinergic synapse).
Acetylcholine binds to receptors on the postsynaptic neuron, leading to various
physiological responses. Acetylcholine that remains in the synapse can be broken down
by the enzyme acetylcholinesterase, and the resulting products are taken back up into the
presynaptic neuron for recycling.
, Receptors: Acetylcholine acts on two main types of receptors: muscarinic receptors and
nicotinic receptors. Muscarinic receptors are G protein-coupled receptors, while nicotinic
receptors are ligand-gated ion channels. Both types of receptors are widely distributed
throughout the body and brain.
It is suggested that a deficiency in serotonin transmission contributes to the
development of depressive symptoms, including obsessions and compulsions.
Norepinephrine also plays a role in mood regulation, and alterations in its levels
or function have been implicated in depression, increasing anxiety, and
disrupting attention.
Some antidepressant medications, such as norepinephrine reuptake inhibitors
(NRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), target both
serotonin and norepinephrine systems.
While dopamine's involvement in depression is not as straightforward as
serotonin and norepinephrine, research suggests that dysregulation of the
dopamine system may contribute to depressive symptoms by altering
attention, motivation, and pleasure.
Some studies propose that an imbalance between dopamine and other
neurotransmitters, like serotonin, might play a role in the pathophysiology of
depression.
Changes in the function of specific dopamine receptors, especially D2
receptors, have been implicated in depression.
Acetylcholine is involved in regulating neural circuits associated with mood
and emotion, particularly in brain regions such as the hippocampus and
prefrontal cortex.
Changes in acetylcholine levels or receptor function in these areas may impact
mood regulation and contribute to depressive symptoms.
Genetic risk factors for developing MDD include the following:
female gender (more common in females than males)
age (at risk of stress during middle age)
close family members with MDD
Environmental risk factors for developing MDD include the following:
death of a close friend or relative
abuse (sexual, physical, psychological)
sleep deprivation
poor nutrition
poor health (cardiovascular, obesity)
poor coping mechanisms or skills
Clinical manifestations of MDD include the following: