Discovering endophenotypes for major depression.

Biochemistry of tryptophan in health and disease.

https://escholarship.org/content/qt58h866d5/qt58h866d5.pdf?t=ntzxig

Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan

Toward a unified theory of serotonin dysregulation in eating and related disorders

Background Evidence suggests that serotonin transporter gene promoter polymorphism( 5HTTLPR )–dependent low transcriptional activity of the human serotonin transporter gene may be a genetic susceptibility factor for depression. We studied the behavioral responses to tryptophan depletion(TD) in healthy women with and without a first-degree family history of depression and examined the relationship to 5HTTLPR alleles. Methods Twenty-four healthy women with a negative family history of depression and 21 women with a positive family history of depression were genotyped for the polymorphism of the 5HTTLPR and then entered a double-blind, placebo-controlled, randomized crossover TD study. The effects of these interventions were assessed with measures of depression and plasma tryptophan levels. Results The TD induced a robust decrease of plasma tryptophan levels in all women irrespective of family history of depression or 5HTTLPR genotypes. The s/s genotype of the 5HTTLPR was associated with an increased risk of developing depressive symptoms during TD irrespective of family history. In contrast, individuals with the l/l genotype did not develop depressive symptoms, irrespective of family history. Finally, s/l subjects without family history showed a mood response that was intermediate between the s/s and l/l subjects, while s/l subjects with a family history of depression showed the same depressiogenic effect of TD as seen in the s/s subjects. Conclusions The results of the present study suggest that the s -allele of the 5HTTLPR and a positive family history of depression are additive risk factors for the development of depression during TD.

https://jamanetwork.com/journals/jamapsychiatry/articlepdf/206543/YOA10200.pdf

Association between serotonin transporter gene promoter polymorphism (5HTTLPR) and behavioral responses to tryptophan depletion in healthy women with and without family history of depression.

Total and free tryptophan concentration in the plasma of depressive patients

Plasma-tryptophan in anorexia nervosa

[Methylene- 14 C]-L-tryptophan was administered intravenously to five patients suffering from severe depression before and after clinical recovery, and to six control subjects; all subjects were tested while on a standard diet. [ 14 C]-5-Hydroxyindoleacetic acid and [ 14 C]-indoleacetic acid were isolated from urine during the following 48 hours and purified to constant specific radioactivity (SA). From the SA and the determination of the total excretion of the two acids their percentage conversion from labelled tryptophan was estimated. There was no consistent difference found, in patients before and after recovery, or between patients and controls, in the conversion of tryptophan to these indole acids. In another series of 11 depressive patients and 11 controls, plasma total (acid-soluble) tryptophan was measured at frequent intervals up to three hours after intravenous administration of a loading dose (1 g) of L-tryptophan. The height of the curves of plasma tryptophan throughout the three hour period was greater than in the depressive patients, even after they had recovered, than in the controls. It is concluded that the apparent volume of distribution of tryptophan is reduced in depressive individuals. This is consistent with other findings of increased protein-binding of plasma tryptophan and reduced CSF tryptophan levels in depressive patients.

Tryptophan metabolism in depressive illness.

Total and free plasma-tryptophan concentration and oral contraception.

Comparison of methods for the determination of total and free tryptophan in plasma.

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