Shmoopers, it ain't called The Heart Is a Lonely Hunter for nothin'. All of our characters are isolated in one way or another, and they have a love-hate relationship with being alone. Of course, it's important to point out that isolation and being alone are by no means the same thing. What's the difference? Well, we get scenes of all our main characters sitting alone and thinking, but that's not always a lonely or bad thing; Mick, for example, likes to sit alone outside a rich person's window, listening to classical music. But isolation? That's a whole other story, and it's definitely not a good thing. These characters are constantly isolated, even when they are surrounded by others. They feel alone inside, mentally, emotionally, spiritually, and that causes all kinds of problems for these lonely hunters.
Jake is totally the most isolated character in the book, both literally and figuratively.
Singer feels most alone when he is surrounded by people, because they can never understand him.