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

Luykx JJ, Bakker SC, van Geloven N, Eijkemans MJ, Horvath S, Lentjes E, Boks MP, Strengman E, DeYoung J, Buizer-Voskamp JE, Cantor RM, Lu A, van Dongen EP, Borgdorff P, Bruins P, Kahn RS, Ophoff RA - Transl Psychiatry (2013)

Bottom Line: Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074).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.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands [2] Department of Psychiatry, ZNA hospitals, Antwerp, Belgium.

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.

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Mean 5-HIAA seasonality values (± s.e.) are shown per 5-HTTLPR genotype: S/S (N=73): 11.39±7.61. S/L (N=192): 0.13±4.96. L/L (N=128): −10.22±5.41.
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fig3: Mean 5-HIAA seasonality values (± s.e.) are shown per 5-HTTLPR genotype: S/S (N=73): 11.39±7.61. S/L (N=192): 0.13±4.96. L/L (N=128): −10.22±5.41.

Mentions: (Figure 3) After genotype quality control (Supplementary Methods), 398 subjects remained, for 393 from whom 5-HIAA levels were available. The genotypes were in Hardy–Weinberg equilibrium (P>0.5) and the numbers of subjects per genotype were: 73 (19%) S/S, 192 (49%) S/L and 128 (33%) L/L. The mean (s.e.) 5-HIAA seasonality values per genotype were: 11.39 (7.61), 0.13 (4.96) and −10.22 (5.41), respectively (Figure 3). A dose-dependent positive association of the s-allele with 5-HIAA seasonality was detected in the models with and without covariates age and sex (β=0.12, P=0.020; and β=0.11, P=0.023, respectively). When excluding subjects on psychotropic mediation or with a self-reported psychiatric history, the results did not change (β=0.12, P=0.019). Neither absolute concentrations of CSF 5-HIAA nor BDI-II scores were associated with the 5-HTTLPR (P=0.2 and 0.8, respectively).


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

Luykx JJ, Bakker SC, van Geloven N, Eijkemans MJ, Horvath S, Lentjes E, Boks MP, Strengman E, DeYoung J, Buizer-Voskamp JE, Cantor RM, Lu A, van Dongen EP, Borgdorff P, Bruins P, Kahn RS, Ophoff RA - Transl Psychiatry (2013)

Mean 5-HIAA seasonality values (± s.e.) are shown per 5-HTTLPR genotype: S/S (N=73): 11.39±7.61. S/L (N=192): 0.13±4.96. L/L (N=128): −10.22±5.41.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818011&req=5

fig3: Mean 5-HIAA seasonality values (± s.e.) are shown per 5-HTTLPR genotype: S/S (N=73): 11.39±7.61. S/L (N=192): 0.13±4.96. L/L (N=128): −10.22±5.41.
Mentions: (Figure 3) After genotype quality control (Supplementary Methods), 398 subjects remained, for 393 from whom 5-HIAA levels were available. The genotypes were in Hardy–Weinberg equilibrium (P>0.5) and the numbers of subjects per genotype were: 73 (19%) S/S, 192 (49%) S/L and 128 (33%) L/L. The mean (s.e.) 5-HIAA seasonality values per genotype were: 11.39 (7.61), 0.13 (4.96) and −10.22 (5.41), respectively (Figure 3). A dose-dependent positive association of the s-allele with 5-HIAA seasonality was detected in the models with and without covariates age and sex (β=0.12, P=0.020; and β=0.11, P=0.023, respectively). When excluding subjects on psychotropic mediation or with a self-reported psychiatric history, the results did not change (β=0.12, P=0.019). Neither absolute concentrations of CSF 5-HIAA nor BDI-II scores were associated with the 5-HTTLPR (P=0.2 and 0.8, respectively).

Bottom Line: Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074).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.

View Article: PubMed Central - PubMed

Affiliation: 1] Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands [2] Department of Psychiatry, ZNA hospitals, Antwerp, Belgium.

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.

Show MeSH
Related in: MedlinePlus