Neurochemical correlation between major depressive disorder and neurodegenerative diseases

Major depressive disorder (MDD) is one of the most prevalent and life-threatening forms of mental illnesses affecting elderly people and has been associated with poor cognitive function. Recent evidence suggests a strong relationship between MDD and neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), Amyotrophic Lateral Sclerosis (ALS), as well as natural processes of aging. Changes in the neuroplasticity, morphology, and neurotransmission in the brain are seem to be associated to both, MDD and neurodegenerative diseases. In addition, there is evidence that psychological stress and MDD are associated with molecular and cellular signs of accelerated aging. This review will highlight the relationship between MDD, the aging process, and neurodegenerative diseases, emphasizing the neurochemical processes involved.

Major depressive disorder (MDD) and Neurodegenerative Diseases pathophysiologic interactions. Patients with MDD have a susceptibility to acquiring Huntington's disease, Alzheimer's Disease (AD), Amyotrophic Lateral Sclerosis (ALS), and Parkinson's Disease (PD); in patients with neurodegenerative diseases there is a higher prevalence of MDD. Elderly individuals with MDD have altered monoamine levels, Hypothalamic-Pituitary-Adrenal (HPA) axis dysfunctions, decreased brain neurotrophic-derived factor (BDNF) levels, morphologic alterations in the brain, and neuroinflammation. MDD and HD both present with changes in the serotoninergic system, primarily serotonin (5-HT) and the 5-HT1A receptor; in addition, brain morphologic changes and decreased neurogenesis are found. AD and MDD share alterations in proteins involved with neural plasticity, such as BDNF and glycogen synthase kinase-3β (GSK-3β). Alterations in amyloid β are also common. Zinc levels, brain morphology changes and neuroinflammation are also shared between AD and MDD. Monoamine alterations are demonstrated in both ALS and MDD. PD and MDD also share altered monoamines, in addition to glutamate and BDNF level changes.Figure optionsDownload high-quality image (103 K)Download as PowerPoint slide