**4. Depression and neurodegenerative diseases**

Depression is considered a neurodegenerative disease, such as Parkinson's disease and Alzheimer's disease. Parkinson's disease with the degeneration of DA neurons of the SNc related to motor function produces motor symptoms, while the degeneration of 5-HT and NA neurons related to mood regulation results in depressed mood and anxiety of patients with depression. In addition, the degeneration of DA neurons of the VTA may be associated with anhedonia in patients with depression. Nonspecific symptoms of depression, such as sleep problems, tiredness, and changes in appetite, may be attributable to the degeneration of 5-HT and NA axons, because loss of these monoamine axons, which are distributed to almost the entire brain, could likely produce a variety of symptoms. A major difference between depression and Parkinson's disease as well as Alzheimer's disease is that the neuropathology of depression is characterized predominantly by the degeneration of axons, while the neurodegenerative changes of Parkinson's disease and Alzheimer's disease include a great loss of the neuron cell somata. The depressive symptoms of patients with depression can occur due to axonal degeneration of monoamine neurons even without soma degeneration, whereas the motor symptoms of Parkinson's disease and cognitive impairment of Alzheimer's disease become evident after the occurrence of soma degeneration. This is well consistent with the fact that depression often precedes symptoms of neurodegenerative diseases, typically including Parkinson's disease and Alzheimer's disease [71, 72]. Thus, depression may be useful as a predictor of the future occurrence of neurodegenerative diseases characterized by cell death. In any case, detection of axonal degeneration before cell death is important for the treatment of Parkinson's disease and Alzheimer's disease. It is noted that DHA supplementation before the onset of dementia results in beneficial outcomes in patients with Alzheimer's disease [55, 73, 74]. Omega-3 supplementation, as a primary intervention, also reduces cognitive decline in patients with mild to moderate Alzheimer's disease [75]. These results suggest that in Alzheimer's disease omega-3 fatty acids reduce mild cognitive impairment by producing axonal regeneration before the occurrence of cell death.
