before vowels phren-, word-forming element meaning "mind," also, in medical use, "diaphragm, muscle which parts the abdomen from the thorax;" from Greek phrēn, phrenos "the mind, spirit," also "the midriff, diaphragm," also (in plural, phrenes) "the parts around the heart, the breast," and hence "wits, sense, sanity, mind" on the notion of the breast or heart as the seat of thoughts and passions.

The word is of uncertain origin; Watkins has it under a proposed PIE root ‌‌*gwhren- "to think." Beekes finds the connection with phrassein "to fence or hedge in" "semantically attractive," but there are phonetic difficulties, and he finds "quite feasible" a relationship with phrazomai "to think, consider" (later phrazein; see phrase (n.)), itself an isolated word.

the later Romans evidently found words beginning in sc-, sp-, st- difficult or unpleasant to pronounce; in Late Latin forms begin to emerge in i- (such as ispatium, ispiritu), and from 5c. this shifted to e-. The development was carried into the Romanic languages, especially Old French, and the French words were modified further after 15c. by natural loss of -s- (the suppression being marked by an acute accent on the e-), while in other cases the word was formally corrected back to the Latin spelling (for example spécial). Hence French état for Old French estat for Latin status, etc. It also affected Romanic borrowings from Germanic (such as espy, eschew).

A different e- is a reduced form of Latin ex- before consonants (see ex-), and the e- in enough is an unfelt survival of an Old English alternative form of ge-.