Personality Change Due to Carcinoid Syndrome?

I was given a paper about a study with a small number of patients, the authors of which concluded that aggression and impulse dyscontrol might be more common in patients with carcinoid syndrome [1]. A psychiatrist examined the patients by using a structured interview. Carcinoids are relatively rare neuroendocrine malignancies that are defined by their tendency to produce and secrete high amounts of serotonin. The serotonin is produced peripherally and cannot pass the blood-brain barrier, so it’s not immediately obvious why this would be connected with aggressive personality changes. However, all of the serotonin produced does cause flushing and diarrhea in the event liver metastases are present.

Serotonin depletion in the periphery may lead to a deficit of serotonin in the brain since tryptophan is a building block of serotonin. However, in the study, plasma tryptophan levels didn’t correlate with impulse control problems. The authors speculate that there may be a relationship between aggression and impulse dyscontrol and excess peripheral serotonin produced by the carcinoid tumor.

By the tryptophan depletion hypothesis, low serotonin in the brain could lead to increased hostility, aggression, and poor impulse control. In fact, low serotonin levels in the cerebrospinal fluid has been linked to aggression in animals, suicide attempts, and certain forms of criminality in humans.

Since there are no medications that patients with carcinoid can tolerate because most of them are serotonergic and cause diarrhea, it might be the case that psychotherapy may be the safest and possibly the most effective form of treatment–which is what psychiatrists typically recommend for most patients who have interpersonal conflict as their main issue.

Well, it’s a small study and anecdotally I can say that the only patient I ever encountered with carcinoid metastatic to the liver was a delightful person with a keenly intelligent and engaging sense of humor. We need more studies before making firm conclusions.

1. Russo, S., J. C. Boon, et al. (2004). “Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation.” Psychosomatic medicine 66(3): 422-425.
OBJECTIVE: Carcinoid tumors can produce excessive amounts of biogenic amines, notably serotonin. We assessed psychiatric symptoms in carcinoid patients and peripheral metabolism of tryptophan, the precursor of serotonin. METHODS: Twenty consecutive patients with carcinoid syndrome underwent a structured psychiatric interview applying DSM-IV (Diagnostical Statistical Manual) criteria. Tumor activity was measured by determination of 24-hour urine excretion of 5-hydroxyindoleacetic acid (5-HIAA) and platelet serotonin levels. Plasma tryptophan levels were measured and compared with sex- and age-matched references. RESULTS: Fifteen patients (75%) fulfilled diagnostic DSM-IV criteria for a disorder of impulse control. Tryptophan plasma levels were lower in patients compared with controls (p =.031) and were correlated negatively with urinary 5-HIAA excretion (p =.001). CONCLUSIONS: Impulse control disorders are prevalent in patients with carcinoid syndrome. The serotonin production by the tumor possibly decreases the tryptophan pool in the cerebrospinal fluid, which is the essential substrate for the production of brain serotonin as a pivotal neurotransmitter.

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Comments

  1. My mother has Carcinoid, and it was not found until it had spread throughout her body, including her liver and spine. I observed definite personality changes in my mother for years before her Carcinoid diagnosis. I had to get psychological counseling for myself to be able to cope with her behaviors. Now when she has outbursts I realize that it’s from the cancer, but it’s still very upsetting.

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    • As medical science proceeds at its usual glacial pace, we can be grateful for the clues that you and others provide that help guide research. Many thanks for your comments.

      Best wishes,

      Jim Amos, MD

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