Major depressive disorder (MDD) is currently the main cause of disability worldwide, but its pathophysiology remains largely unknown, especially given its high heterogeneity in terms of clinical phenotypes and biological characteristics. Accordingly, its management is still poor. Increasing evidence suggests that oxidative stress, measured on various matrices such as serum, plasma or erythrocytes, has a critical role in MDD. The aim of this narrative review is to identify serum, plasma and erythrocyte biomarkers of oxidative stress in MDD patients according to disease stage and clinical features. Sixty-three articles referenced on PubMed and Embase between 1 January 1991, and 31 December 2022, were included. Modifications to antioxidant enzymes (mainly glutathione peroxidase and superoxide dismutase) in MDD were highlighted. Non-enzymatic antioxidants (mainly uric acid) were decreased in depressed patients compared to healthy controls. These changes were associated with an increase in reactive oxygen species. Therefore, increased oxidative damage products (principally malondialdehyde, protein carbonyl content and 8-hydroxy-2′-deoxyguanosine) were present in MDD patients. Specific modifications could be identified according to disease stages and clinical features. Interestingly, antidepressant treatment corrected these changes. Accordingly, in patients in remission from depression, oxidative stress markers were globally normalized. This narrative review suggests the particular interest of oxidative stress biomarkers for MDD care that may contribute to the heterogeneity of the disease and provide the opportunity to find new therapeutic targets.

For psychotic disorders (i.e. schizophrenia), pharmacotherapy plays a key role in controlling acute and long-term symptoms. To find the optimal individual dose and dosage strategy, specialized tools are used. Three tools have been proven useful to personalize drug treatments: therapeutic drug monitoring (TDM) of drug levels, pharmacogenetic testing (PG), and molecular neuroimaging. In these Guidelines, we provide an in-depth review of pharmacokinetics, pharmacodynamics, and pharmacogenetics for 50 antipsychotics. Over 30 international experts in psychiatry selected studies that have measured drug concentrations in the blood (TDM), gene polymorphisms of enzymes involved in drug metabolism, or receptor/transporter occupancies in the brain (positron emission tomography (PET)). Study results strongly support the use of TDM and the cytochrome P450 (CYP) genotyping and/or phenotyping to guide drug therapies. Evidence-based target ranges are available for titrating drug doses that are often supported by PET findings. All three tools discussed in these Guidelines are essential for drug treatment. TDM goes well beyond typical indications such as unclear compliance and polypharmacy. Despite its enormous potential to optimize treatment effects, minimize side effects and ultimately reduce the global burden of diseases, personalized drug treatment has not yet become the standard of care in psychiatry.

Background: Human dermal fibroblasts (HDF) can be used as a cellular model relatively easily and without genetic engineering. Therefore, HDF represent an interesting tool to study several human diseases including psychiatric disorders. Despite major depressive disorder (MDD) being the second cause of disability in the world, the efficacy of antidepressant drug (AD) treatment is not sufficient and the underlying mechanisms of MDD and the mechanisms of action of AD are poorly understood.Objective: The aim of this review is to highlight the potential of HDF in the study of cellular mechanisms involved in MDD pathophysiology and in the action of AD response.Methods: The first part is a systematic review following PRISMA guidelines on the use of HDF in MDD research. The second part reports the mechanisms and molecules both present in HDF and relevant regarding MDD pathophysiology and AD mechanisms of action.Results: HDFs from MDD patients have been investigated in a relatively small number of works and most of them focused on the adrenergic pathway and metabolism-related gene expression as compared to HDF from healthy controls. The second part listed an important number of papers demonstrating the presence of many molecular processes in HDF, involved in MDD and AD mechanisms of action.Conclusion: The imbalance in the number of papers between the two parts highlights the great and still underused potential of HDF, which stands out as a very promising tool in our understanding of MDD and AD mechanisms of action.

Aim: The antidepressant venlafaxine (VEN) is metabolized by CYP2D6 and CYP2C19. The aim of this study was to assess the relevance of generalizing to daily practice the genotyping of CYP2D6 and CYP2C19 to predict VEN efficacy in depressed patients treated in psychiatric settings. Patients & Methods: This study was nested in a naturalistic cohort, with 206 patients requiring a new antidepressant treatment and genotyped for CYP2D6 *3, *4, *5 del, *6, *2xN, *10, *41 and CYP2C19 *2, *3, *4, *5, *17 alleles. Results: CYP2D6 and CYP2C19 phenotypes were associated neither with the Hamilton depression rating scale score improvement, nor with response and remission. Conclusion: Routine CYP2D6 and CYP2C19 genotyping cannot be recommended to predict VEN efficacy in depressed patients treated in psychiatry settings.