One reason why the cast of this book might be a touch on the Lonesome side might be simply that they have secrets. They believe that their pasts are too incriminating to share with others, and in some cases that is literally the case. Throughout the book, the reader gets to know characters, and then when they have been in the story awhile, more information about them is revealed. That helps to point the reader to an ironic idea, that everyone is probably hiding something.
For the beginning of this thematic interpretation, look at the conversation Gus has with the prostitute in the opening sequences. He wants to pay her for her secrets, specifically asking her to recount the tale of her becoming a prostitute. But, even though Gus could pay her for sex, even though he could literally have paid to use her body as a sexual object, she refuses to let him buy her secrets.
Contrast that with the mid-novel revelation that Jack has murdered someone before. Ben Johnson lived in Arkansas when Jack took his life, and there is a brother hoping to hunt Jack down. This means the secret is alive and dynamic, because Jack needs for people to never find out who he really is and what his past contains, because that might help the brother track him down for vengeance. Therefore, the book suggests that secrecy is of the utmost importance to people who have done horrific things, but that makes them isolated, because no one really knows anything about the "real" them.
