Stress is known to have a significant impact on mental health. While gender differences can be found in stress response and mental disorders, there are limited studies on the neuronal mechanisms of gender differences in mental health. Here, we discuss gender and cortisol in depression as presented by recent clinical studies, as well as gender differences in the role of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in stress-associated mental disorders. When examining clinical studies drawn from PubMed/MEDLINE (National Library of Medicine) and EMBASE, salivary cortisol generally showed no gender correlation. However, young males were reported to show heightened cortisol reactivity compared to females of similar age in depression. Pubertal hormones, age, early life stressors, and types of bio-samples for cortisol measurement affected the recorded cortisol levels. The role of GRs and MRs in the HPA axis could be different between males and females during depression, with increased HPA activity and upregulated MR expression in male mice, while the inverse happened in female mice. The functional heterogeneity and imbalance of GRs and MRs in the brain may explain gender differences in mental disorders. This knowledge and understanding will support the development of gender-specific diagnostic markers involving GRs and MRs in depression.

Major depressive disorder (MDD) patients commonly encounter multiple types of functional disabilities, such as social, physical, and role functioning. MDD is related to an accreted risk of brain atrophy, aging-associated brain diseases, and mortality. Based on recently available studies, there are correlations between notable biological brain aging and MDD in adulthood. Despite several clinical and epidemiological studies that associate MDD with aging phenotypes, the underlying mechanisms in the brain remain unknown. The key areas in the study of biological brain aging in MDD are structural brain aging, impairment in functional connectivity, and the impact on cognitive function and age-related disorders. Various measurements have been used to determine the severity of brain aging, such as the brain age gap estimate (BrainAGE) or brain-predicted age difference (BrainPAD). This review summarized the current results of brain imaging data on the similarities between the manifestation of brain structural changes and the age-associated processes in MDD. This review also provided recent evidence of BrainPAD or BrainAGE scores in MDD, brain structural abnormalities, and functional connectivity, which are commonly observed between MDD and age-associated processes. It serves as a basis of current reference for future research on the potential areas of investigation for diagnostic, preventive, and potentially therapeutic purposes for brain aging in MDD.

Introduction: Treatment‐resistant depression (TRD) is a condition in which patients suffering from depression no longer respond to common methods of treatment, such as anti‐depressant medication. Neurosurgical procedures such as ablative surgery, deep brain stimulation, and vagus nerve stimulation have been used in efforts to overcome TRD.Objectives: This review aims to provide an overview of the side effects of neurosurgery performed in clinical studies related to depression.Methods: A literature search was conducted through PubMed, MEDLINE, EMBASE, Ovid, and ClinicalTrials.gov databases.Results: This review selected 10 studies for ablative surgery, 12 for deep brain stimulation, and 10 for vagus nerve stimulation, analyzing their side effect profiles of neurosurgery for TRD. The major side effects of each type of neurosurgery were identified, such as incontinence and confusion for ablative surgery, headaches and increased suicide ideation for deep brain stimulation, and voice hoarseness and dyspnea for vagus nerve stimulation.Conclusion: The review discusses the merits and demerits of neurosurgery as a treatment option for TRD. It also suggests new insights into decreasing the burden of these neurosurgical side effects so that they can be a viable, high‐efficacy treatment method for TRD.