Describe the pathophysiology of depression

Describe the pathophysiology of depression.
Depression is a psychiatric disorder characterized by a persistent feeling of sadness, depressed mood, and loss of interest in various activities, causing significant daily life impairment.
People can generally be sad after an adverse event happened in their lives, such as losing a job or a loved one but will recover from the event. Depression is a persistent feeling of sadness that lasts about two weeks. The feeling of depression must be accompanied by five or more of the most common symptoms of depression: a change in appetite, losing or gaining weight, sleeping too much, insomnia, fatigue, low energy, feeling helpless, inability to focus, or even suicidal ideation.  These symptoms must cause clinically significant distress or impairment in social, occupational, or other important functioning areas. Besides, the individual must not have any history of a manic or hypomanic episode.
Scientists believe that depression is a connective abnormality in the cortico-limbic network. There is an imbalance of connectivity between the prefrontal cortex and one or all of the brain’s limbic regions: hippocampus, amygdala, and hypothalamus. It seems like that under depression, the volume of the hippocampus decreases. There are three neurotransmitters responsible for these neuro-connections between the cortical region and the limbic regions. These neurotransmitters are dopamine, serotonin, and norepinephrine. It is important to note that serotonin is the primary neurotransmitter regulating communication between the prefrontal region and the limbic region. In addition, serotonin also regulates the mood and the level of norepinephrine and dopamine in the brain. It is believed that depletion of these neurotransmitters is the cause of depression. Several other factors can contribute to depression, such as physical health issues, including cancer, a recent loss of limb, certain medications such as cortical steroid, oral contraceptive, family history of depression, environmental factors, and stress. Stress, for example, increases the cortisol level, which may decrease serotonin level. At this time, no unitary mechanism of depressant action has been found. The relationship among serotonin, norepinephrine, dopamine, acetylcholine needs further assessment and study. However, treatment with medication that helps regulate these neurotransmitters has proved empirically successful in treating many patients.
References
McCance, K. L.,