In the fifth season finale, the character retired from his monster-hunting lifestyle after the apparent death of his brother Sam (Jared PadeleckI) and settled down with girlfriend Lisa (Cindy Sampson) and her son.
The showrunner told TV Squad that the new season was "an opportunity to tell a lot of story about Dean. If you've been in a relationship of any length, it has stakes, to the point where you're living with someone and you're raising their child with them."
She added that Dean would be reluctant to rejoin his brother after he returns in mysterious circumstances.
"There's real affection [between Dean and Lisa], so you don't just pack up your s**t and go," she explained. "It's a conversation for them both to have."
Gamble also confirmed that Dean would not be driving his beloved Chevrolet Impala in the beginning of the season.
"It's under a tarp, and when he needs something from the trunk, he just lifts up the edge," she said. "The Impala represents everything to Dean. It represents his childhood, and more to the point, it represents hunting and it represents Sam. He's not a hunter anymore and his brother is dead, so it's under a tarp and he's living a different life."
Supernatural will return to The CW on September 24.