Diabetes mellitus is a strong molecular etiological upstream event that leads to different pathological problems like Cardio-vascular
disease, nephropathy, neuropathy, retinopathy, hearing loss, and immunological disturbances, the most common of which is
depression. Diabetes and depression relationship is thought to be bidirectional, meaning that depression can lead to diabetes and
diabetes can assist the onset of depression. Depression is one of the most overlooked symptoms in diabetes patients, and it is strongly
related to a decline in quality of life. Several pathological links are discussed in this review, including dysregulation of the hypothalamic
pituitary-adrenal (HPA) axis and neurotransmitter systems, particularly the monoaminergic system, the role of oxidative stress,
neuroinflammation, and cell death, impaired neurogenesis and BDNF synthesis, particularly in the hippocampus and prefrontal cortex, brain areas that regulate emotional behaviour, and finally, epigenetic factors.
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