The neuroprogressive nature of major depressive disorder: pathways to disease evolution and resistance, and therapeutic implications

• Published in: Molecular psychiatry Vol. 18; no. 5; pp. 595 - 606
• Main Authors: Moylan, S, Maes, M, Wray, N R, Berk, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2013; Nature Publishing Group
• Subjects: 631/378/340; 692/420; 692/699/476/1414; 692/700/565; Adult and adolescent clinical studies; Animals; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain - metabolism; Brain - pathology; Brain - physiopathology; Brain research; Care and treatment; Depression; Depressive Disorder, Major - complications; Depressive Disorder, Major - pathology; Depressive Disorder, Major - therapy; Disease Progression; Disease resistance; Encephalitis - etiology; Epigenetics; Humans; Hypothalamus; Illnesses; Inflammation; Major depressive disorder; Medical imaging; Medical research; Medical sciences; Medical treatment; Medicine; Medicine & Public Health; Mental depression; Mental health; Methods; Mitochondria; Molecular modelling; Mood disorders; Neurogenesis; Neuroimaging; Neuropsychology; Neurosciences; Neurotransmitter Agents - metabolism; Neurotrophic factors; original-article; Oxidative stress; Oxidative Stress - physiology; Oxidoreductases - metabolism; Patients; Pharmacotherapy; Physiological aspects; Pituitary; Prevention; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychotherapy; Australia; nitrosative stress; cytokines; depression; inflammation; neuroprogression; oxidative stress; Mood disorder; Oxidative stress; Treatment; Cytokine; Depression; Evolution; Inflammation
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/mp.2012.33

In some patients with major depressive disorder (MDD), individual illness characteristics appear consistent with those of a neuroprogressive illness. Features of neuroprogression include poorer symptomatic, treatment and functional outcomes in patients with earlier disease onset and increased number and length of depressive episodes. In such patients, longer and more frequent depressive episodes appear to increase vulnerability for further episodes, precipitating an accelerating and progressive illness course leading to functional decline. Evidence from clinical, biochemical and neuroimaging studies appear to support this model and are informing novel therapeutic approaches. This paper reviews current knowledge of the neuroprogressive processes that may occur in MDD, including structural brain consequences and potential molecular mechanisms including the role of neurotransmitter systems, inflammatory, oxidative and nitrosative stress pathways, neurotrophins and regulation of neurogenesis, cortisol and the hypothalamic–pituitary–adrenal axis modulation, mitochondrial dysfunction and epigenetic and dietary influences. Evidence-based novel treatments informed by this knowledge are discussed.