Bill Hader and Kristen Wiig in "The Skeleton Twins"

Before raising the curtain on his second feature “The Skeleton Twins” at the Egyptian Theatre during the Seattle Film Festival, Craig Johnson recalled how he’d take in all the delightful oddities that the festival had to offer as a student at the University of Washington, specifically Kirby Dick’s documentary “Sick” about sadomasochist Bob Flanagan, in the very seats he could see from the stage. Although Johnson wasn’t making the direct connection between those and the movie he was about to show, “The Skeleton Twins” definitely arrives from a place off the beaten path, a slightly unsettling and deeply amusing dark comedy that finds Kristen Wiig and Bill Hader as Maggie and Milo, a sister and brother reunited after a ten-year cold spell in their relationship when Milo’s suicide attempt fails.

There clearly remains a psychic link between the two since Maggie’s holding a fistful of pills herself when she gets the call about Milo. But everything else is out of sync between the siblings when they reconnect, from Maggie fearing she spoiled the ending to “Marley and Me” for Milo while he recovers in the hospital to when they awkwardly attempt to clink wine glasses over dinner when they get back to the home she shares with Lance (Luke Wilson), an amiable working class type who’s eager to start a family. The cause of their individual discontent becomes obvious as Maggie continues to take birth control without Lance’s knowledge and Milo speaks of hitting a dead end as an actor in Hollywood.

But the root of their discontent with one another is less so since Johnson and co-writer Mark Heyman obscure the reasons behind their break a decade earlier. Vague references to a relationship between Milo and his high school English teacher (Ty Burrell), who still lives in town, and allusions to the siblings’ parents, their New Agey mother (Joanna Gleason) who now lives in Sedona and their father, who committed suicide himself and is mentioned but never seen in flashbacks to their less than fond memories of growing up, are offered as hints.

This may not appear to be the stuff for the comedy one might expect (and eventually receive) from a film starring Wiig and Hader, but in pushing everyone from the actors to the audience out of their comfort zone, Johnson finds a happy medium between subversive laughs and serious introspection, or unhappy as the circumstances here may be. An unwillingness to be pegged down tonally contributes to the general air of mystery the film creates.

There’s a dim, almost fuzzy surreality to the way Reed Morano shoots the family’s hometown in upstate New York in the days leading up to Halloween that has the two stuck as if they were trudging out of molasses, the initial thought that Maggie is further along in life than Milo with a house and a husband can be discarded as soon as you realize, unlike Milo, she still lives amongst many of her high school classmates who she never liked. For his part, Milo can speak eloquently about how he peaked in high school and is quick to size up others and yet struggles to gauge others’ perception of him.

While their characters may not bring the best out of one another, Wiig and Hader do, bringing an unmistakable authenticity to siblings who trade playful teasing and vicious barbs in equal measure. I’ve been impressed before by Wiig’s ability to say so much with so little, but both she and Hader give layered performances that take time to reveal themselves, with each radiating the surprise of learning more about who they really are as the film wears on. Luke Wilson also shines as Lance, the lone bastion of stability in the house, his normality a reliably amusing source of irritation for Maggie and Milo.

But as much as the characters that populate “The Skeleton Twins” strive to be normal, Johnson’s film stands out for avoiding it like the plague, confidently finding its own strange, poignant wavelength that can accommodate an epic rendition of Starship’s “Nothing’s Gonna Stop Us Now” and the quiet contemplation of those who realize they are their own worst enemy and unsure of a way forward. During a scene when Milo wonders aloud what’s so special about “Moby Dick” with his old English teacher, he is told, “Who gives a shit when the writing is that weird and funny and alive?” In that moment, it’s easy to feel the same way about “The Skeleton Twins.”

“The Skeleton Twins” will be distributed later this year by Roadside Attractions.