Betrayal
The main theme confronted by the novel is the redemption of family relationships after serious betrayals. For instance, Dianna, the mother, is locked into an affair behind her husband's back. The twins each sabotage each other in their own ways. Noah hides Jude's work from their mother, and Jude throws his art school application away.
Guilt and shame
Guilt and shame are explored thoroughly in the novel. For instance, Noah is shamed by his mother for his attraction to boys, and he feels guilt for his mother's death. Jude's shame about sex (her mother died the same night Jude lost her virginity) is also paired with guilt for their mother's death, so much that Jude can't focus enough each day to pass her classes.
Redemption
In betrayal, shame, regret, or guilt, the novel is very clear about the path forward. It's not the despair of Noah's drunken suicide attempt, but rather, suffering should lead to deeper confessions of honesty and love that make the way for true hope. This happens at the end when the couples each admit their affections, and when the twins reconcile their years of regrets.