Seasonal variation of serotonin turnover in human cerebrospinal fluid, depressive symptoms and the role of the 5-HTTLPR

J J Luykx, S C Bakker, N van Geloven, M J C Eijkemans, S Horvath, E Lentjes, M P M Boks, E Strengman, J DeYoung, J E Buizer-Voskamp, R M Cantor, A Lu, E P A van Dongen, P Borgdorff, P Bruins, R S Kahn, R A Ophoff

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.

Original languageEnglish
Article numbere311
Pages (from-to)1-6
Number of pages6
JournalTranslational Psychiatry [E]
Volume3
Issue number10
DOIs
Publication statusPublished - 8 Oct 2013

Keywords

  • Adult
  • Alleles
  • Depression/cerebrospinal fluid
  • Female
  • Homovanillic Acid/cerebrospinal fluid
  • Humans
  • Hydroxyindoleacetic Acid/cerebrospinal fluid
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Regression Analysis
  • Seasons
  • Serotonin/cerebrospinal fluid
  • Serotonin Plasma Membrane Transport Proteins/genetics

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