The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) reduces depression-like behavior in mice by suppressing neuroinflammation and neuronal pyroptosis. In experiments with male C57BL/6J mice and PC12 cells, HNK lowered expression of NLRP3, caspase-1, GSDMD, and interleukin-1β at both protein and mRNA levels, lessened neuronal injury, and reduced lactate dehydrogenase release. Transcriptomic analysis identified Vcam1 as a key differentially expressed gene. Overexpressing Vcam1 increased pyroptosis markers, while HNK reduced Vcam1 expression; knocking down Vcam1 had opposite effects. HNK thus attenuates LPS-induced pyroptosis and neuroinflammation partly by downregulating the Vcam1/caspase-1/IL-1β pathway, offering insights for depression treatment.
Adolescents who value self-transcendence (e.g., caring for others) tend to want more socially engaging emotions like empathy and love, while those who value self-enhancement (e.g., personal success) do not show a clear preference for socially disengaging emotions like anger. In one study, teens rated their values and desired emotions; in another, they chose images to view. Teens with stronger self-transcendence values chose more social and neutral images than those with stronger self-enhancement values. The findings support a value-based account of desired emotions in adolescents.
Adolescents in China who prioritized self-transcendence and openness to change values reported less depression and loneliness, while those who prioritized self-enhancement and conservation values reported more depression and loneliness. Four value clusters emerged: self-focus, other-focus, anxiety-free, and undifferentiated. Adolescents in the anxiety-free cluster had the lowest depression and loneliness, whereas those in the other-focus cluster had the highest. Regional differences appeared only for depression: adolescents in Shanghai reported higher depression than those in Qingdao.