When he was on a visit to Scotland in his young manhood, he met an older distant cousin, Isabella Clark, and was very charmed by her and they married.  At the time that he met her she was extremely healthy. But he brought her home to Kingston to live with his mother and his older unmarried sister.
    Whether it was the climate of Kingston or living with your mother-in-law, to  whom, by the way, he was always very close, because having a weak father, he had a very strong, formative and supportive mother, no one really knows, but Isabella's health started to fail. And I researched that very, very carefully. I found an article by a doctor who is a university professor, who thought that her illness was partly psychosomatic. But in Macdonald's letters, he refers to her, constantly, as having a painful tic....Reading between the lines, I would even venture the idea that she may have had tri-geminal neuralgia, because of the extreme pain that she was always in and the fact that Kingston is a very damp and windy climate. She was much improved in health when he took her every winter down to Virginia or even Philadelphia, which was his custom.  
    In spite of that, they seemed to have a happy marriage. She was an invalid, but doctors at that time tended to prescribe laudanum, which was, in fact, opium. So his wife was addicted to opium, and he openly refers to that in the letters around the birth of his first child, a little boy, who lived for thirteen months and then died of an unknown cause. But he refers to the birth of the child who was tall but skinny, as being in remarkable health in spite of the fact that his mother was addicted. It's right in his letters.