Michael Maes, MD, M.D. Ph.D.

JAD profile

Affiliation(s): 

Chulalongkorn University; Deakin University; Medical University of Plovdiv

Areas of Interest: 

neurocognition, peripheral blood biomarkers, MCI, MBI, dementia, oxidative stress, inflammation, depression, psychosis

Biography & Research: 

SHORT CURRICULUM VITAE Prof. Dr. Michael Maes is a translational neuroscience scientist whose research includes epidemiological and clinical investigations, case-control studies, pharmaceutical trials, as well as rodent and molecular experiments. Dr. Maes is since 2003 a highly cited author (ISI, Thomson Reuters) with a H-index >140 and > 79.000 citations. He is listed in the Webometrics Ranking of World Universities as one of the Top Scientists (2016) and to belong to the 0.01% top of all scientists worldwide (Standardized citation data annotated for scientific field for multiple impact indicators). He is ranked worldwide #1 in ME/CFS, #1 in oxidative stress, #1 in encephalomyelitis, #1 in nitrosative stress, #1 in nitrosation, #1 in tryptophan, #2 in bacterial translocation, #2 in stress, physiological, #3 in inflammation, #2 in neuroimmune, #5 in depression, #5 in fatigue, #4 in psychiatry, #7 in depressive disorder, #7 in melancholia, #7 in affective disorders, #7 in mood disorders, #9 in cytokines (Bibliometric Website Expertscape, September 2022). He published more than 950 scientific papers in peer-reviewed international journals and gave more than 300 invited lectures at different international symposia. His work has been published in peer-reviewed journals, including Molecular Psychiatry, Molecular Neurobiology, Acta Psychiatrica Scandinavica, Psychiatry Research, Biological Psychiatry, Neuropsychobiology, BMC Medicine, Neuroscience & Biobehavioral Reviews, Journal of Affective Disorders, Cells. The work of Dr. Maes covers the supra-multi-disciplinary field of “pathway and drug discovery processes” in neuro-psychiatric disorders. Dr. Maes's research is focused on biomarkers, pathways and molecular networks of psychiatric disorders, such as major depression, chronic fatigue syndrome, bipolar disorder and schizophrenia, and its comorbid disorders including Parkinson’s disorder, multiple sclerosis, lupus erythematosus, stroke, rheumatoid arthritis and Alzheimer’s disease. Dr. Maes discovered that “clinical depression (MDD/MDE)” is a systemic illness characterized by peripheral a) increases in pro-inflammatory cytokine levels (1990) with an acute phase or inflammatory response (1992); b) cell-mediated immune (CMI) activation (1990); c) lowered omega-3 PUFA levels (1996); d) lowered plasma tryptophan, which determines brain serotonin contents, is an inflammatory sequel (1993); e) f) lowered antioxidant defenses against lipid peroxidation as indicated by lowered LCAT and HDL, and increased atherogenicity (1994); g) bacterial translocation and associated autoimmune responses due to increased gut permeability (leaky gut and gut-brain axis: 2007-2022); and h) increased nitrosylation (2006). Dr Maes laboratories also discovered that immune-inflammatory and neuro-oxidative stress pathways determine depressive symptoms in comorbid disorders or conditions including: IFNα-based-immunotherapy (depression is caused by increased synthesis of neurotoxic tryptophan catabolites (2000), end stage chronic kidney disease, multiple sclerosis, cardiovascular disorders (including unstable angina), type 2 diabetes mellitus, rheumatoid arthritis, transfusion-dependent thalassemia, schizophrenia, COVID-19, temporal lobe epilepsy, stroke, and apical peridontitis (2016-2022). Dr. Maes discovered that antidepressants and mood stabilizers normalize the Th-1/Treg ratio and that curcumin acts as an antidepressant. Dr. Maes also developed a new machine-learning-based method to diagnose mood disorders using a new approach, namely Research and Diagnostic Algorithmic Rules (RADAR), indicating that the DSM/ICD diagnoses of MDE/MDD/BD and the RDoC methods are inadequate. RADAR allows one to score early lifetime trauma (ELT), lifetime suicidal ideation and attempts, recurrence of illness (ROI), the phenome of mood disorders, and the overall suicidal behaviors and lifetime trajectory, and to display an idiosyncratic fingerprint profile of the patient in a RADAR graph (2022). Using supervised/unsupervised learning, Dr. Maes showed that the key component of mood disorders is ROI (including suicidal behaviors, mania and depressive episodes) and that the latter is driven by ELT, lowered paraoxonase 1 (PON1) activity and PON1 genotype, deficits in the PON1+HDL complex, lipid peroxidation and sensitization of the immune-inflammatory and growth factor networks. Other ground-breaking discoveries were that a) psychological stressors may cause immune activation, inflammation and Th1 responses in humans (1995-2000); b) Chronic Fatigue Syndrome is a serious medical disorder with activated immune-inflammatory and neuro-oxidative stress pathways, immunosuppression, increased bacterial translocation and autoimmunity (2001-2022); c) perinatal depression and PMS (re-labeled as MCAS or menstrual cycle-associated syndrome) are neuro-immune and neuro-oxidative conditions (1997-2022); d) vulnerability factors such as lowered peptidase activities, anti-cytokines (e.g. CC16), natural protective autoimmune responses (2005-2022) and antioxidant defenses play key roles in mental disorders (1990-2022); and e) acute and Long-COVID are associated with increased depressive, chronic fatigue and physiosomatic symptoms (re-labeled as the physio-affective phenome of COVID-19), which are driven by inflammatory pathways during acute infection and neuroimmunotoxic, NLRP3 inflammasome and neuro-oxidative stress pathways and depleted antioxidant defenses during Long COVID. In 1995, Maes et al. also launched the monocyte-T lymphocyte theory of schizophrenia considering that activated immuno-inflammatory pathways may account for the higher neurodevelopmental pathology linked with gestational infections through the detrimental effects of activated microglia, oxidative and nitrosative stress, cytokine-induced activation of the tryptophan catabolite pathway and consequent modulation of the NMDAR. Recently, Dr. Maes discovered that deficit schizophrenia is a neuro-immune disorder characterized by a) increased neuroimmunotoxicity; b) increased gut bacterial translocation due to breakdown of the paracellular pathway; c) lowered natural innate immunity and antioxidant defenses against inflammation, bacterial infections and oxidative stress (1994-2022). Using Machine Learning (ML), Dr Maes developed a new endophenotype class of schizophrenia (based on Kraepelin’s defect schizophrenia and the newer deficit schizophrenia criteria), namely “major neurocognitive psychosis” which is a qualitative distinct class with specific disorders in the above pathways. These neuroimmunotoxic disorders, deficits in the innate immune system and increased neuro-oxidative stress are associated with specific neurocognitive impairments, which should be conceptualized as a generalized cognitive decline (G-DoDe) (2018-2022). The clinical and translational work of Dr. Maes contributed to the delineation of new drug targets in mood disorders and schizophrenia, thereby opening the way to novel treatments of psychiatric disorders, such as add-on treatments with ω3-PUFAs, antioxidants, curcumin, anti-inflammatory compounds, minocycline, etc.