Major depressive disorder (MDD) has a widespread heterogeneity as per the psychiatric nosology, and traditional symptom-based diagnosis frameworks do not offer many clues regarding tailored therapy techniques. The recent development of multi-omics and data-driven solutions has now provided evidence for pathophysiologically different subtypes of MDD, moving the field toward precision psychiatry. The systematic review aggregates multimodal studies that combing neuroimaging, genomics, transcriptomics, epigenomics, metabolomics, and proteomics to define MDD subtypes. There are two to four candidate clusters that have been formed across these heterogeneous modalities, and each has a neurobiological and clinical profile. Cognitive subtypes are characterized by executive failure and loss of prefrontal and temporal gray matter. Neuroimaging-derived subtypes show specific patterns of functional connectivity that may predict response to selective serotonin reuptake inhibitors (SSRIs) or repetitive transcranial magnetic stimulation (rTMS) in preliminary studies. There are immune-metabolic subtypes characterized by increased inflammatory cytokines and dysregulation of metabolic pathways. Molecular subtypes appear to be differentiated by cellular mechanisms such as mitophagy and pyroptosis. Taken together, these results indicate that multi-omics integration, in addition to explaining the molecular architecture of MDD, also characterizes patient subgroups with pathophysiological mechanisms, dimensions of symptoms, and disease treatment. The growing body of literature demonstrates that there is a shift in psychiatry toward a more mechanistic approach and that biomarker-based diagnostics and personalized treatment regimens are urgently needed to improve clinical outcomes in depressive diseases.
E. Amjad, B. Sokouti· OBM Neurobiology· 0 citations
The pathology of PD is characterized by progressive degeneration of dopaminergic neurons, although the full regulatory network involved in this process is not yet fully established. The present research employed a multi-omic systems biology design, integrating transcriptomic, functional, epigenetic, and microRNA analyses to develop a mechanistic model of neurodegeneration in the substantia nigra. We have determined six differentially expressed genes, such as tyrosine hydroxylase (TH), solute carrier family 18 member 2 (SLC18A2/VMAT2), and engrailed 1 (EN1), that are of critical interest in the disruption of the dopaminergic synapse and the inability to load vesicular neurotransmitters (fold enrichment: 2164.22). Notably, we have identified a candidate dual regulatory axis underlying the silencing of these neuroprotective genes. In this mechanism, repressive histone marks (H3K27me3 and H3K9me3) are concurrent, and post-transcriptional repression via specific microRNAs, in particular, hsa-miR-431-3p (EN1) and mmu-miR-362-5p (SLC18A2), is involved. The combined model thus finds a mutual dysregulation of epigenetics and microRNA as the main cause of gene silencing. Besides, the Traditional Chinese Medicine (TCM) components were analyzed to identify compounds that can interact with the core targets (TH and SLC18A2), thereby providing translational potential. The results identify candidate TCM compounds predicted to interact with core targets (TH and SLC18A2), providing hypothesis-generating leads for multi-target interventions that may modulate the repressive epigenetic landscape, suppress regulatory microRNAs, and engage dopaminergic pathways. Predicted interactions require experimental validation to distinguish beneficial modulation from potential inhibition. This would seek to reverse severe neuronal activity and halt the advancement of Parkinson's disease. These findings illustrate a neuro-nutrigenomic application in which dietary-derived and herbal compounds may modulate gene expression and epigenetic marks in Parkinson’s disease.