The interplay between inflammation, oxidative stress, DNA damage, DNA repair and mitochondrial dysfunction in depression

The Phosphodiesterase Inhibitor Pentoxifylline as a Novel Adjunct to Antidepressants in Major Depressive Disorder Patients: A Proof-of-Concept, Randomized, Double-Blind, Placebo-Controlled Trial

“…One of the most substantial anti-inflammatory cytokines is IL-10, which possesses an inhibitory action on proinflammatory cytokines [12,13]. Furthermore, individuals with MDD show a significantly higher level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage, than controls [14,15].…”

Mitochondrial DNA m.13514G>A heteroplasmy is associated with depressive symptoms in the elderly

“…Our results indicate that the heteroplasmy load identified in the eighth decade of life is associated with elevated depressive symptoms in men but not in women. Mitochondrial dysfunction is a frequent early event in several neurodegenerative illnesses and may be operative in patients with mood disorders and late‐life depression . This mitochondrial dysfunction leads to lower observed levels of high‐energy phosphates in the brain, which have been shown to impair executive function and other cognitive processes in late‐life depression .…”

“…Several psychiatric disorders exhibit substantially high levels of oxidative DNA damage in the brain accompanied with morphological and functional alterations, which may contribute to the pathophysiology of these mental illnesses . Increased oxidative stress in combination with impaired DNA damage repair may in part be responsible for increased DNA damage in depressed patients . Shortened telomere length has been observed in persons with major depression and with depressive symptoms; however, associations with mtDNA copy number have not been conclusive.…”

“…Mitochondrial dysfunction is an especially important characteristic of late‐onset neurodegenerative diseases, mood disorders, and psychiatric disorders . In particular, damage to the mitochondrial electron transport chain has been suggested as an important factor in the pathogenesis of a range of neuropsychiatric disorders, including depression . For example, decreased mitochondrial respiratory rate may play a role in pathophysiology of depression in humans .…”

“…Multiple biological causes may underlie age-related depression including mitochondrial functioning, oxidative damage, dopaminergic neurotransmission, and inflammation. [17][18][19] Mitochondrial dysfunction is an especially important characteristic of late-onset neurodegenerative diseases, 20 mood disorders, 21 and psychiatric disorders. 22 In particular, damage to the mitochondrial electron transport chain has been suggested as an important factor in the pathogenesis of a range of neuropsychiatric disorders, including depression.…”