Nutrient Imbalances in Depressive Disorders Possible Brain Mechanismsa

Abstract

We examined the utility of d-fenfluramine, a serotonin-releasing drug previously shown to diminish carbohydrate craving and weight gain in obese people, in treating patients with seasonal affective disorder (SAD), a variant of depression that occurs each fall and winter and is usually associated with hyperphagia and carbohydrate craving. Eighteen patients participated in a double-blind, placebo-controlled study in 1986-1987, each receiving, in random order, d-fenfluramine (15 mg p.o. twice daily) or a placebo for four weeks, separated by a two-week washout period. Symptoms of SAD were assessed before and after each treatment period using clinical interviews by a psychiatrist, and the Hamilton Depression Rating Scale (HDS) with a special SAD addendum (ADD). Subjects were also weighed. Patients' depression scores (mean +/- SEM) were identical before treatment with drug (20.9 +/- 1.3, HDS: 13.3 +/- 0.8 ADD) or placebo (21.4 +/- 1.2, HDS; 13.2 +/- 0.6 ADD). During placebo treatment, HDS scores declined by 22.6% (p less than 0.02) and ADD scores by 9% (p greater than 0.2). During d-fenfluramine treatment, HDS scores fell by 71% (p less than 0.0001) and ADD scores by 73% (p less than 0.0001). Thirteen of the subjects (72%) demonstrated complete reversal of their abnormal test scores on d-fenfluramine. In two others, test scores fell to normal levels with both the drug and its placebo; one subject responded only to placebo; and two failed to show therapeutic responses to either drug or placebo treatment. The group as a whole lost weight (1.2 kg) on d-fenfluramine (p less than 0.033) but not on placebo. A subsequent study on nine of the responders showed that improvements persisted for the full three-month duration of the SAD season. These results indicate that d-fenfluramine, a drug not previously identified as an antidepressant, may be useful in treating SAD. Moreover, since d-fenfluramine acts specifically to enhance serotonin-mediated neurotransmission, the data further suggest that serotonin is involved in both the affective and appetitive symptoms of SAD. Indeed, the carbohydrate craving of these patients may constitute a kind of substance abuse in which the nutrient is eaten precisely for its serotonin-mediated psychotropic effects.

Food preferences in human obesity: Carbohydrates versus fats

“…Since other amino acids compete with tryptophan for uptake into the brain, overconsumption of protein/fat mixtures should aggravate serotonin imbalance in susceptible obese persons, reducing satiety and causing depression and fatigue. Finally, since carbohydrates with a high glycemic index most effectively promote tryptophan uptake by the brain and so redress serotonin imbalance, foods such as potato starch ought to be the most common object of food cravings (Wurtman et al, 1989).…”

(N-3) Fatty Acids: Molecular Role and Clinical Uses in Psychiatric Disorders

“…It is widely accepted that the PUFA have an important role in many neural pathways and that their deficiency may be correlated with the occurrence of several psychiatric illnesses, such as major depression, bipolar disorder, obsessive-compulsive disorder, and anxiety disorders (10)(11)(12)(13)(14). Exploration of these mechanisms of action has inspired the pursuit of new treatment protocols that feature PUFA as an adjunctive or as a monotherapy for treatment of these diseases, with many surprising results.…”

Understanding nutrition, depression and mental illnesses

“…[20232427283033] Accumulating evidence from demographic studies indicates a link between high fish consumption and low incidence of mental disorders; this lower incidence rate being the direct result of omega–3 fatty acid intake. [233132] One to two grams of omega-3 fatty acids taken daily is the generally accepted dose for healthy individuals, but for patients with mental disorders, up to 9.6 g has been shown to be safe and effective.…”