A Fatal Connection

By Samantha Wong

“I met my wife when I was seventeen. I didn’t want to tell her about my schizophrenia. At the time, she liked another guy who had no issues and I didn’t want to ruin my chances. I hid the disease for a long time after we married. I would always find explanations for my strange behavior. I’d make up stories to explain my violent outbursts at work. But it got to be too much. By the time I admitted my disease, it was too late. She got a restraining order a year ago. I had an outburst and I hit her. She has forgiven me for the sake of our children, but they don’t live with me anymore. I’m on five strong medications now. I still have some difficulty controlling the pace of my thoughts. Some thoughts will begin before others end. It’s like my mind is divided. It can be tough to keep both feet in reality. But I don’t want any more problems. I’ve detached myself from everyone. I don’t speak at work. I spend my time alone. It’s my only way to live a normal life.”

The above Humans of New York post illustrates the realities of the rare and very debilitative disorder schizophrenia. Affecting 0.5 to 1% of the global population, schizophrenia is multifactorial neuropsychiatric disorder in which one is affected by three classes of symptoms: positive, negative, and cognitive. Positive symptoms, or things “added” that aren’t normal, include hallucinations, delusions, and agitated movements. Negative symptoms, or things “subtracted” that are normal, include flat affect, reduced or disorganized speech, and difficulty initiating and sustaining behaviors. Cognitive symptoms or deficits include poor decision-making, decreased working memory function, and difficulty focusing or paying attention. Those with a severe mental illness like schizophrenia have mortality rates 2–3 times higher than the general population, which equates to a loss of 10–20 years of life per person.

The man in the excerpt above states that he takes five different medications now. Most likely, those medications are a combination of antipsychotics, the common prescribed treatment of schizophrenia symptoms. Antipsychotics are also known to treat other disorders such as autism, dementia, and delirium. They were first developed in the 1950s and are, today, known as first-generation antipsychotics. A couple examples are Chorpromazine and Haloperidol. However, these first-generation antipsychotics were soon found to have numerous adverse side effects, like hypotension, weight gain, sexual dysfunction, sedation, and extrapyramidal effects (movement problems). Thus, second-generation antipsychotics began to be developed, aimed at reducing the majority of these problems. While they succeeded for the most part in ridding the user of sedative and extrapyramidal effects, they did not prevent the inevitable and accompanying weight gain in the patient. Thus follows a linkage between two disorders, one psychiatric and one metabolic, that is far more common than we realize.

Diabetes mellitus affects approximately 12% of those who have a severe mental illness like schizophrenia. For these people, diabetes is associated with higher rates of microvascular and macrovascular complications (so, affecting the cardiovascular system), and acute metabolic dysregulation and death. The problem is that we know the facts, but we don’t know the cause. Like schizophrenia, the link between diabetes and schizophrenia is multifactorial; there are most likely many underlying factors contributing to the dangerous linkage. Just like we don’t know the true cause of schizophrenia, we don’t know the true cause of this link, making it difficult to find a cure. We can only treat the symptoms in the meantime.

Concerns have been raised about the adverse metabolic effects of the antipsychotics, attributing them to the cause. There are two important themes that seem to be undeniable across many different research papers: 1) antipsychotic treatment is associated with a higher prevalence of diabetes than with no treatment, and 2) treatment with a second-generation antipsychotic is associated with a small increase in risk of developing diabetes as compared to treatment with a first-generation antipsychotic.

Antipsychotics might increase risk of developing diabetes directly — by increasing insulin resistance or reducing insulin secretion — or indirectly by increasing body weight. Again, the increase in body weight is an inevitable effect of taking the medications. Studies have been done to show that those who did not take the treatment before and had a steady baseline weight showed marked increases in weight within 4 months of treatment. However, while it may be tempting to attribute the link between schizophrenia and diabetes to this weight gain, it should be noted that there are patients with schizophrenia who develop diabetes who did NOT show an increase in weight gain. The drugs have many effects on many different receptors, not just insulin receptors. Also, we can’t exactly blame the antipsychotics alone for the cause of diabetes, because other risk factors like obesity, poor diet, physical inactivity, and family history all come into play. For instance, patients with schizophrenia, with their poorer decision-making skills, will be less likely to exercise and more likely to live a sedentary lifestyle and eat unhealthy foods.

This particular dilemma is sure to be a head-scratcher. Further studies are being done to examine this linkage, but one thing seems to be sure (forgive my lack of a better phrase): when the world screws you over, it screws you over hard.

Citations

Holt, Richard I. G. & Mitchell, Alex J. (2015). Diabetes mellitus and severe mental illness: mechanisms and clinical implications. Nat. Rev. Endocrinol. 11, 79–89.