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As a consequence of the biochemical reactions in which homocysteine is involved, deficiencies of vitamin B 6, folic acid (vitamin B 9), and vitamin B 12 can lead to high homocysteine levels. [2] Other possible causes of hyperhomocysteinemia include genetics, excessive methionine intake, and other diseases.
For example, when glutamate receptors such as the NMDA receptor or AMPA receptor encounter excessive levels of the excitatory neurotransmitter, glutamate, significant neuronal damage might ensue. Excess glutamate allows high levels of calcium ions (Ca 2+) to enter the cell.
Based on the monoamine hypothesis of depression, which asserts that decreased concentrations of monoamine neurotransmitters leads to depressive symptoms, the following relations were determined: "Norepinephrine may be related to alertness and energy as well as anxiety, attention, and interest in life; [lack of] serotonin to anxiety, obsessions ...
Glutamate receptors and impaired regulation (in particular, those resulting in excessive glutamate levels) are also one cause of excitotoxicity (described above), which itself has been implicated or associated with a number of specific neurodegenerative conditions where neural cell death or degradation within the brain occurs over time. [42] [46]
Glutamate is the most abundant excitatory neurotransmitter in the vertebrate nervous system. [60] Increased glutamate excitatory activity during withdrawal may lead to sensitization or kindling of the CNS, possibly leading to worsening cognition and symptomatology and making each subsequent withdrawal period worse.
Despite its longstanding prominence in pharmaceutical advertising, the idea that low serotonin levels cause depression is not supported by scientific evidence. [ 12 ] [ 13 ] [ 14 ] One interpretation is that depression manifests due to an imbalance of neurotransmitters in the brain, resulting in feelings of worthlessness and despair.
[162] [163] This network is involved in high level cognitive functions such as maintaining and using information in working memory, problem solving, and decision making. [ 161 ] [ 164 ] Deficiencies in this network are common in most major psychiatric and neurological disorders, including depression.
Excessive glutamate release is a known major cause of neuronal cell death. Glutamate causes neurotoxicity due to excitotoxicity and oxidative glutamate toxicity. Evidence from animal studies suggests that some people may be more genetically sensitive to the neurotoxic and brain damage associated with binge drinking regimes.