Psilocybin, a serotonergic psychedelic, shows therapeutic potential for depression and anxiety disorders. In a study using serotonin transporter knockout mice—a model for anxiety and depression—a single dose of psilocybin (1 mg/kg) failed to produce head-twitch or hyperlocomotor responses in knockout animals, unlike wild-type mice. Psilocybin did not alter anxiety- or depressive-like behaviors in either genotype, though a trend toward reduced immobility in the Porsolt swim test appeared in female wild-type mice. Female knockout mice uniquely showed anhedonia-like behavior. The findings indicate that functional serotonin transporters are necessary for psilocybin's acute behavioral effects, with implications for pharmacogenetics in humans.
Mindfulness meditation reduces depression during pregnancy. A meta-analysis of 10 randomized controlled trials with 658 participants found a positive effect (standardized mean difference = −0.786). Mindfulness-based cognitive therapy was the most effective intervention. The best results came from programs lasting less than 4 weeks, applied throughout pregnancy, with expert guidance fewer than 6 times per week for sessions under 60 minutes, plus daily 30-minute homework. High heterogeneity across studies was partly due to different depression measurement tools, notably the Beck Depression Inventory-II. Mindfulness meditation can help prevent and reduce pregnancy depression and may serve as an auxiliary clinical treatment.
Mice lacking the serotonin transporter (5-HTT KO mice) model SSRI-resistant depression, showing no response to the SSRI sertraline in the forced-swim test, unlike wild-type mice. Ketamine, an NMDAR antagonist, produced antidepressant-like effects in both genotypes, suggesting it works independently of 5-HTT function. The KO mice also had reduced locomotor responses to NMDAR antagonists and lower hippocampal GluN2A protein, indicating glutamatergic dysfunction. These results support ketamine's effectiveness in treatment-resistant depression and offer a model to study its mechanisms.