According to the National Institute of Mental Health (NIMH) more than 16 million Americans suffer from Major Depressive Disorder, representing over 6 percent of the population. Of that 6 percent, the depression rate of females is nearly double that of males. Many people dismiss depression as simply choosing to be in a bad mood or have a negative outlook on life. Due to the stigma around mental illness, this attitude—though unfortunate— is not surprising. However, the statistics alone reveal that depression is a much more real issue than many think. The more scientists research the matter, the more evident it is becoming that depression is a real mental illness just like Schizophrenia or Dementia. The depression so far referred to is more properly called Clinical Depression. People often say they feel depressed when they experience a temporary negative mood. However, clinical depression is much more than simply being upset or having a negative mood; it is an illness that can cause severe dysfunctional effects such as hopelessness, restlessness, agitation, indecision, altered sleep and appetite, fatigue, slower movements, the inability to feel pleasure, a loss of concentration, and all too often, suicide. This paper will deal specifically with clinical depression. Although there are many types of clinical depression—Major Depressive Disorder (MDD), Persistent Depressive Disorder (PDD), Bipolar Disorder, Psychotic Depression, and Postpartum depression (PPD) to name a few—I will not distinguish between them. The goal of this paper is to achieve a better understanding of what is generally happening inside the brain of a clinically depressed person. The research on this matter is far from conclusive. In fact, doctors have far more questions about depression than answers. Nevertheless, significant discoveries have been made regarding the neurological implications of depression which I hope to detail. This matter is of particular interest to me as my sister has struggled for years with depression and has contended that antidepressant drugs have saved her life. What is going on in the brain of a person like my sister? How and why do antidepressants alleviate depression? Why is depression much more common in females than males? These are some of the questions I seek to answer. To begin at a surface level, depression is often claimed to be due to a chemical imbalance in the brain. Scientists have long held that a deficiency of the neurotransmitter serotonin causes depression symptoms. Neurotransmitters aid in the transportation of signals in the brain from one neuron to the next. When patients with depression are given SSRI antidepressants which increase serotonin in the brain, their depression symptoms are often cured. However, it is still uncertain if serotonin actually causes depression. A study done on mice unable to produce any serotonin failed to confirm this theory; the mice lacking serotonin showed no signs of depression. Recent research is, in fact, showing that depression is more complicated than a simple lack of serotonin. Although chemical imbalance plays a role, there are also factors such as nerve cell connections genetics and stress which play a role. One significant discovery is that the brains of depressed people are structurally different than the brains of nondepressed people. In particular the Hippocampus, a part of the brain which controls memory and emotion, is significantly smaller than normal in depressed patients. One recent study showed indicated the hippocampus in individuals suffering from depression was 9 to 13 percent smaller than average. (See Figure 1 to see a comparison of the size of the Hippocampus in depressed brains compared to normal brains.) In other words, depression is not just “all in your head;” rather, it results from actual damage to the Hippocampus. Stress is often cited as a cause of neuron deterioration in the Hippocampus.