The present invention relates to a method for identifying a TMEFF2 modulator, comprising (a) contacting a cell which expresses TMEFF2 with a candidate compound to be tested; (b) measuring whether said compound to be tested decreases or increases the level of a constituent of the cAMP signalling pathway, preferably the CRH signalling pathway, in said cell when compared to a corresponding cell which does not express TMEFF2; (b′) optionally determining whether said compound is capable of reduncing the binding between Activin and TMEFF2; and (c) identifying said modulator compound. Furthermore, a method for identifying a TMEFF2 modulator comprising determining whether said TMEFF2 modulator is capable of reducing the binding between Activin and TMEFF2 is contemplated. It also relates to uses and methods applying a TMEFF2 agonist for the treatment of Cushing's Syndromes and a TMEFF2 modulator for the treatment of affective disorders. Furthermore, methods of diagnosing affective disorders or Cushing's Syndromes are provided.