Depression is the most commonly diagnosed mental illness, yet antidepressants are either effective only after prolonged treatment or remain largely ineffective. Mazella et al. identified a naturally occurring peptide, spadin, as a fast-acting antidepressant that interacts with, and blocks the activity of, a mood-regulating potassium channel, TREK-1. Mice lacking TREK-1 are resistant to depression and exhibit behavior similar to mice treated with antidepressants. Spadin-treated mice displayed a similar resistance to depression as TREK-1-deficient mice within only four days, as opposed to the several weeks necessary to respond to conventional therapies. Short-term spadin treatment induced classical antidepressant markers including increased CREB expression and neurogenesis. Unlike current depression medication, spadin’s rapid onset of action makes it a strong candidate to develop novel and more successful antidepressant medication.

Mazella
J
,
Pétrault
O
,
Lucas
G
,
Deval
E
,
Béraud-Dufour
S
,
Gandin
C
,
El-Yacoubi
M
,
Widmann
C
,
Guyon
A
,
Chevet
E
, et al. 
(
2010
).
Spadin, a sortilin-derived peptide, targeting rodent TREK-1 channels: a new concept in the antidepressant drug design
.
PLoS Biol
.
8
,
e1000355
.