The default mode network (DMN) is a set of brain regions active during rest and self-referential thought. This review of studies up to August 2016 examined how DMN functional connectivity varies in healthy people by age, sex, cognitive function, and analysis method. DMN connectivity follows an inverse U-shape across the lifespan: strongest in adulthood, lowest in children and the elderly. Cognitive function positively correlates with DMN connectivity. Females show stronger intranetwork connectivity than males. Effects of analysis type were inconclusive. A voxel-wise meta-analysis for age confirmed an immature network in children versus adults and a stronger network in adults versus the elderly. Defining normal variation may help identify DMN changes in pathology.
A systematic review by the Canadian Network for Mood and Anxiety Treatments evaluated evidence for racemic ketamine in treatment-resistant depression. Single intravenous infusions have Level 1 evidence for efficacy in adults, while multiple or maintenance infusions have only Level 3 evidence. Adverse events include dissociative symptoms and hypertension. Non-IV formulations have Level 3 or 4 evidence. Single-dose IV racemic ketamine is a third-line recommendation; repeated use requires careful case-by-case risk-benefit assessment. Oral and other formulations should be limited to specialists with ketamine expertise at tertiary centers due to limited evidence and risk of misuse.
Serotonergic psychedelics are being reconsidered as potential treatments for major depressive disorder. A Canadian task force systematically reviewed clinical trials from 1990 to 2021 and found that only psilocybin and ayahuasca have been tested in contemporary studies. Two pilot studies of single-dose ayahuasca for treatment-resistant depression showed preliminary positive effects (Level 3 evidence). Small randomized controlled trials of psilocybin combined with psychotherapy for major depressive disorder showed superiority to waitlist controls and comparable efficacy and safety to escitalopram with supportive psychotherapy, with additional trials showing efficacy in cancer-related depression (Level 3 evidence).