Brain Serotonin, Carbohydrate‐Craving, Obesity and Depression

Serotonin-releasing brain neurons are unique in that the amount of neurotransmitter they release is normally controlled by food intake: Carbohydrate consumption--acting via insulin secretion and the "plasma tryptophan ratio"--increases serotonin release; protein intake lacks this effect. This ability of neurons to couple neuronal signaling properties to food consumption is a link in the feedback mechanism that normally keeps carbohydrate and protein intakes more or less constant. However, serotonin release is also involved in such functions as sleep onset, pain sensitivity, blood pressure regulation, and control of the mood. Hence many patients learn to overeat carbohydrates (particularly snack foods, like potato chips or pastries, which are rich in carbohydrates and fats) to make themselves feel better. This tendency to use certain foods as though they were drugs is a frequent cause of weight gain, and can also be seen in patients who become fat when exposed to stress, or in women with premenstrual syndrome, or in patients with "winter depression," or in people who are attempting to give up smoking. (Nicotine, like dietary carbohydrates, increases brain serotonin secretion; nicotine withdrawal has the opposite effect.) It also occurs in patients with normal-weight bulimia. Dexfenfluramine constitutes a highly effective treatment for such patients. In addition to producing its general satiety-promoting effect, it specifically reduces their overconsumption of carbohydrate-rich (or carbohydrate-and fat-rich) foods.