Association between urinary neurotransmitter levels and the development of depressive symptoms in a general Japanese population: The Hisayama Study

We investigated the association between urinary neurotransmitter levels and the risk of the presence of depressive symptoms cross-sectionally, as well as the longitudinal risk of their development. A total of 2321 participants aged ≥40 years were enrolled in the cross-sectional analysis using the data from a baseline survey (2012-2013). Of these, 1654 participants without depressive symptoms at baseline were included in the longitudinal analysis using the data of both the baseline and follow-up surveys (2017-2018). Six urinary neurotransmitters-dopamine, homovanillic acid (HVA), vanillylmandelic acid (VMA), serotonin, 5-hydoroxyindoleacetic acid (5-HIAA], and gamma-aminobutyric acid (GABA)-were measured using liquid chromatography-mass spectrometry and corrected by urinary creatinine levels. Participants were categorized into sex-specific quartiles. Depressive symptoms were assessed by the Patient Health Questionnaire-9 (PHQ-9, ≥10 points). Odds ratios (ORs) for depressive symptoms were calculated using a logistic regression model. In the cross-sectional analysis, multivariable-adjusted ORs of the presence of depressive symptoms increased significantly with decreasing urinary levels of dopamine (Q1: 4.16 [95% confidence interval: 2.43-7.10] vs. Q4), serotonin (Q1: 2.60 [1.58-4.29] vs. Q4), and VMA (Q1: 2.75 [1.68-4.49] vs. Q4) (all P for trend <0.01). In the longitudinal analysis, 61 participants developed depressive symptoms. The multivariable-adjusted ORs of the development of depressive symptoms increased significantly with decreasing urinary dopamine levels (Q1: 2.57 [1.05-6.33] vs. Q4). Our findings suggest that lower urinary neurotransmitter levels are associated with an increased risk of both the presence and development of depressive symptoms in the general Japanese population.