Motivation is indispensable for Achievement. It is associated with Success, Intelligence, Happiness.Depression and Anxiety deplete Humoral Neurotransmitters.

What differs Depression from Sadness.

The DSM defines Sadness as an average period of two weeks characterized by low-mood as result of transient disappointment.

Although the symptoms are equal to Depression, it is not treated pathologically.
It is thought that occasional Sadness empowers us towards inevitable life sorrows, an antidote to Depression, ironically.

Low-mood over two weeks is classified as Clinical Depression.
An overly simplistic model to me.

Is Neurotransmission compromised in Sadness?

Debatable dilemma if we see Sadness medically, either referred to as ‘Adjustment Disorder’ or ‘Situational Depression’.
Some Mental Health Professionals consider the condition as the precursor of Clinical Depression, henceforth starting patients on antidepressants.
Others support Counseling beforehand, both preventative measures.

The controversy is that antidepressants take at least 3/4 weeks to work, therefore they are not worth the effort for temporary Sadness.
Nonetheless, low-mood can deplete neurotransmitters for Compensation.
On the other hand, Clinical Depression is a post-synaptic disease.

It would look like Compensation occurs at pre-synaptic level, excluding Receptors’ activity. Given the assumption, SSRIs will downplay their performance.
The question is whether dormant neurotransmitters are pre-synaptically effective.

It is established that Sadness increases the amount of necessary neurotransmitters, in so doing, depriving neurons.
Insufficient neurotransmitters would prevent the ‘sending-receiving-reuptake s pattern,’ aka Neurotransmission.

Put it bluntly, neurotransmitters are disabled in the absence of intercellular connectivity.
SSRIs don’t enhance neurotransmitters production, they enhance neurotransmission.
In essence, they don’t help with depleted neurons.

It is paramount to understand where humoral neurotransmitters- Serotonin, Dopamine, Adrenaline- originate from.

Their hormonal nature leads to Adrenal Glands.

Adrenal glands release either deficient or excessive neurotransmitters in response to stress and lack of sleep.

It is unclear if antidepressants target the Endocrine System.
Adrenal glands are part of the Endocrine System however, the Brain produces its own Serotonin in the Brainstem, Dopamine in the Substantia Nigra, Adrenaline in the Medulla Oblongata.

The neurotransmitters produced in the Adrenal Glands don’t cross the Blood-Brain-Barrier.
Their interaction is not known.

Dopamine is the predominant cerebral neurotransmitter, with Serotonin and Adrenaline accounting for as little as 5%.
95% of Serotonin is synthesized in the gut, whereas Adrenaline would act as Neurohormone in the brain, kind of dopamine precursor. The large amount is synthesized in the Adrenal Glands and spread throughout the body by means of Circulation in the function of Modulator.
Brainstem Serotonin exerts Mood Stabilization through the Spinal Cord and Prefrontal Cortex.

The line between Hormones and Neurotransmitters is very thin and poorly defined.

A new branch of Neuroscience named the “Gut-Brain Axis” is being developed.

More research is needed.