Video 1: depression_ treatment

 Introduction to depression: people feel: lonely, empty, excessive, tired

 Definition of depression:
- Feeling of severe despondency and dejection (oxford)
- Disorders of mood (don’t disturbances of thought or cognition)
 Symptoms of depression
1. Low mood
2. Loss of interests or pleasure in most activities
3. Fatigue
4. Insomnia or hypersomnia
5. Changes in appetite and/or weight loss
6. Feeling of worthlessness, excessive or inappropriate guilt
7. Psychomotor agitation or retardation
8. Diminished ability to think/concentrate or increased indecision
9. Recurrent thoughts of death, suicidal thoughts, or actual suicide attempts
 Types of depression
- Subthreshold depressive symptoms: <5 symptoms
- Mild depression: >5 symptoms
- Moderate depression: between mild and severe
- Severe depression: most symptoms
 Monoamine theory: is used to explain the cause of depression. It state that
depression is due to the deficiency of monoamine neurotransmitter especially
norepinephrine (NE) and serotonin (5-HT). In the normal synapse, an impulse is sent
to the presynapse and the vesicles release the mono min which is serotonin for here
into the synapse the receptors on the postsynaptic serotonin and transmitter, the
impulse further the serotonin reuptake is carried out after transmission completed the
output is almost the same as the input for a person who suffer from depression the
Mahnomen present in the presynaptic is less than that in normal person hence less
serotonin is released into the synapse and the receptor are not fully occupied.
Therefore the impulse transmittered out is less than that transmitted in. In another
words the output is less than the input the serotonin is then reuptake by presynapse.
 Types of antidepressants
1. Selective serotonin Reuptake Inhibitors (SSRIs)
2. Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs)
3. Atypical Antidepressants
4. Tricyclic Antidepressants (TCAs)
5. Monoamine Oxidase Inhibitors (MAOIs)
 SSRIs/SNRIs
Selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake
inhibitors are similar mechanism of action which is blocking the reuptake of mono
man thus more monoamine stay in the synapse and allow further transmission. The
difference between SSRI and SNRI is SNRI selectively inhibit the reuptake of
Norepinephrine and serotonin.
 Atypical antidepressants
- Different effects on monoamine neurotransmitter
- Example: bupropion is weak dopamine and noren reuptake inhibitor whereas
mirtazapine enhances serotonin and nor every neurotransmission
 Tricyclic antidepressants
- Mechanism of action same as SNRIs
- Block receptor
- Example: drug under this category are climate permanent docks pain
 Monoamine Oxidase Inhibitors
- Before we discuss the mechanism of action of monoamine oxidase inhibitors, we
have to understand the role of monoamine oxidase my oxidatively demon ate and
inactivate any excess neurotransmitters to prevent leaking out of synaptic vesicles.
However this causes lack neurotransmitter in the synapse this can be prevented by
monoamine oxidase inhibitors.
Video 2: serotonin and depression
Serotonin, or 5-hydroxytryptamine, is a neurotransmitter involved in many brain and body
functions and is commonly known as the substance of well-being and happiness.
Serotonin is produced in specialized neurons found mostly in the Raphe nuclei located
along the midline of the brainstem. The axons of these neurons form extensive
serotonergic pathways that reach almost every part of the central nervous system,
including the cerebellum and the spinal cord. This is why it’s not surprising that serotonin
is implicated in a vast array of brain functions, including sleep and wake cycle, appetite,
mood regulation, memory and learning, temperature, control,… among others.
Serotonin is synthesized from the amino acid tryptophan and is stored in small vesicles
within the nerve terminal. When a serotonergic neuron is stimulated, serotonin is
released into the synaptic cleft where it binds to and activates serotonin-receptors on the
postsynaptic neuron. Serotonin action is then TERMINATED via removal of its molecules
from the synaptic space. This is accomplished through a special protein called serotonin-
transporter.
Low levels of serotonin in brain have been associated with depressive disorders and
current treatments for depression aim to increase levels.
The most commonly prescribed medications, called “selective serotonin reuptake
inhibitors”, or SSRIs, act by blocking serotonin reuptake by the transmitting neurons.
This results in elevated levels of serotonin in the synaptic space and its prolonged action
on the receiving neuron. The SSRIs have developed into the drugs of choice because
they produce fewer side effects thanks to their selective action on serotonin alone and no
other neurotransmitters.
Unfortunately, because serotonin is involved in a wide range of brain function, the side
effects remain significant and may progress to a potentially dangerous condition know as
serotonin syndrome. This syndrome is generally caused by a combination of two or more
drugs used to raise the serotonin levels in the brain. If the medications are not
discontinued, the condition may become fatal.
Nonpharmacologic methods of raising brain serotonin have shown promising results in
recent studies. It has been suggested that positive mood induction, either self-induced or
due to psychotherapy, correlates with INCREASED serotonin synthesis in the brain. The
interaction between serotonin synthesis and mood may therefore be 2-way, with
serotonin influencing mood and mood influencing serotonin. Other methods include
exposure to bright light and tryptophan-rich diets. To note, however, that serotonin-rich
food such as bananas would NOT work because serotonin unlike tryptophan, can NOT
cross the blood brain barrier. Finally, although it sounds like a cliché, physical exercise
maybe the most effective and safe way of improving mood. Several studies suggest that
serotonin levels are increased with vigorous physical activity and that these elevated
levels are maintained for several days after the exercise.