HYPOTHESIS

The depression postulates that neuronal plasticity is a key factor in the development of
depression and in the clinical response to antidepressants. Brain-derived neurotrophic factor (BDNF) is
an important protein in this process. The serum level was found to be consistently lower in depressed
patients compared to healthy controls. In short open-label antidepressant treatment trials the levels
were found to be higher post-treatment than pre-treatment. Longitudinal analysis of a large naturalistic
cohort study revealed that it was more likely that serum levels were lower as a result of depression than
that they represented an etiological factor for the illness.

Antidepressant medications have been found to increase the flow of monoamine

neurotransmitters. These kinds of neurotransmitters are responsible for the treatment of this mood
disorder. This theory has become a famous theory as mentioned before but particularly, in West Europe
and USA after fighting off some studies about biometrics. The monoamine theory of depression has
expanded on the pathophysiological assumptions about the actions of antidepressant medications.
These monoamine neurotransmitters include adaptive changes in receptors and can explain that gradual
clinical response is present after the antidepressant intervention.

Monoamine oxidase A (MAO-A) is an enzyme which grows monoamines and may be

hyperactive in depressed people. The monoamine of depression came from the discovery that the lack
of monoamine neurotransmitters can trigger depression. This kind of therapy is a famous
neurophysiological theory that explains this kind of mood disorder. This also comes from the benefits of
serotonin that is used in antidepressant medications. The monoamine oxidase inhibitors (MAOI) are
agonists of dopamine, norepinephrine, epinephrine, and serotonin.
Due to these kinds of neurotransmitters, antidepressants can affect dominant symptoms of depression.
For instance, people with this kind of mood disorder who has irritable mood should be more at an
advantage when they take SSRIs or norepinephrine reuptake inhibitors.
People with depression who have the loss of energy being dominant can take norepinephrine and
dopamine enhancing medications.

Depression is caused by the underactivity in the brain of monoamines, such as dopamine,

serotonin, and norepinephrine. It is a biological theory stating that depression is caused by the
underactivity in the brain of monoamine, such as dopamine, serotonin, and norepinephrine. In the
1950's the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants were accidentally
discovered to be effective in the treatment of depression. These findings and other supporting evidence
led Joseph Schildkraut to publish his paper called "The Catecholamine Hypothesis of Affective Disorders"
in 1965. Schildkraut associated low levels of neurotransmitters with depression. Research into other
mental impairments such as schizophrenia also found that too little activity of certain neurotransmitters
were con nected to these disorders.
 Depression is a mental disorder characterised by clinical symptoms including low mood,
rumination, functional impairment, retardation, and somatic syndromes such as sleep disturbances and
loss of appetite. Antidepressants were serendipitously discovered in the 1950s, when Iproniazid, a drug
originally prescribed as a treatment for tuberculosis, was shown to induce increased vitality and desire
for social activity in patients (López-Muñoz & Alamo, 2009).

It had been previously observed that Iproniazid was capable of inhibiting monoamine-oxidase (MAO), a
family of enzymes the oxidation of monoamines such as serotonin and noradrenaline. The connection
scientists made between an improved mood in patients with tuberculosis and higher levels of
monoamines in their brains led to further research into MAO inhibitors (MAOIs) as a treatment for
depression and what is now known as the monoamine hypothesis – which poses that depression is
caused by a deficiency in serotonin and noradrenaline in the brain.

According to this, it is possible to restore normal function in depressed patients by increasing the levels
of monoamines at the synaptic level. This theory has been ubiquitous for the past fifty and has been said
to have inaugurated the modern psychopharmacological era in psychiatry (Healy,1997). Over the course
of these years Iproniazid gave way to other agents which are more effectively inhibiting MAO (Jacobsen,
1986). These monoamine reuptake inhibitors (MRI) prevent the removal of monoamines from the
synaptic area, thus increasing the overall concentration of monoamines in the brain .

Then, in addition to these mixed outcomes, studies at the biological level show that synaptic
concentrations of serotonin and noradrenaline are in fact not lower than normal in all individuals
suffering from depression, nor do these individuals have fewer monoamine receptors in their brain,
challenging the validity of the monoamine hypothesis. The central role of monoamine levels in the onset
of depression is further challenged by the delay between increase in monoamine levels in the brain and
clinical improvement.