Metabolomic markers of antepartum depression and suicidal ideation.

BACKGROUND: Recent analyses have described metabolomic markers for depression and suicidal ideation in non-pregnant adults. We examined the metabolomic profile of antepartum depression and suicidal ideation during mid-pregnancy, a time of high susceptibility to mood disorders. METHODS: We collected fasting blood from 100 pregnant Peruvian women and profiled 307 plasma metabolites using liquid chromatography-mass spectrometry. We used the Patient Health Questionnaire 9 to define antepartum depression (score  ≥ 10) and suicidal ideation (having thoughts that you would be better off dead, or of hurting yourself). Logistic regression was used to calculate odds ratios (ORs). RESULTS: Three triacylglycerol metabolites (C48:5 triacylglycerol [OR = =1.89; 95% confidence interval (CI): 1.14-3.14], C50:6 triacylglycerol [OR = =1.88; 95%CI: 1.13-3.14], C46:4 triacylglycerol [OR = =1.89; 95%CI: 1.11-3.21]) were associated with higher odds of antepartum depression and 4 metabolites (betaine [OR = =0.56; 95%CI:0.33-0.95], citrulline [OR = =0.58; 95%CI: 0.34-0.98], C5 carnitine [OR = =0.59; 95%CI: 0.36-0.99], C5:1 carnitine [OR = =0.59; 95%CI: 0.35-1.00]) with lower odds of antepartum depression. Twenty-six metabolites, including 5-hydroxytryptophan (OR = =0.52; 95%CI: 0.30-0.92), phenylalanine (OR = =0.41; 95%CI: 0.19-0.91), and betaine (OR = =0.53; 95%CI: 0.28-0.99) were associated with lower odds of suicidal ideation. LIMITATIONS: Our cross-sectional study could not determine whether metabolites prospectively predict outcomes. No metabolites remained significant after multiple testing correction; these novel findings should be replicated in a larger sample. CONCLUSIONS: Antepartum suicidal ideation metabolomic markers are similar to markers of depression among non-pregnant adults, and distinct from markers of antepartum depression. Findings suggest that mood disorder in pregnancy shares metabolomic similarities to mood disorder at other times and may further understanding of these conditions' pathophysiology.

Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria.

One of the three pathways for the metabolisation of dietary tryptophan is the formation of serotonin. Tryptophan hydroxylase catalyses the formation of 5-hydroxytryptophan, the first and regulatory step of this biosynthesis. The aim of the present work is to study alterations in this tryptophan metabolism in rats with experimental Porphyria Cutanea Tarda induced by hexachlorobenzene. With this purpose, the content of tryptophan and its metabolites related to the serotonin pathway are determined by HPLC techniques, in tissues (brain, liver and gut) and in fluids (blood, plasma and urine) of controls and hexachlorobenzene-porphyric rats. In these experimental-porphyric animals, we determine a significant increase in the excretion of 5-hydroxyindole acetic acid in urine and a decrease in the content of serotonin in small gut, respect to controls. Significant increases in contents of serotonin in 24-hr urine and tryptophan in liver are also found. No other significant variations for the different metabolites are detected in any of the tissues and fluids studied. Brain and liver activities of the rate-limiting enzyme tryptophan hydroxylase can only be measured in porphyric rats. Our results agree with an increased turnover of gastrointestinal serotonin derived from dietary tryptophan and its excretion as urinary 5-hydroxyindole acetic acid, which is formed in liver. An increased serotonin pathway in porphyric livers is confirmed by the measured increase in the activity of hepatic tryptophan hydroxylase. The absence of neurological symptoms in patients with Porphyria Cutanea Tarda could be related to the absence of a statistically significant variation in serotonin content shown in brain.