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.
Highlights
Seasonal variation in monoaminergic transmission may be one of the mechanisms explaining circannual fluctuations in behavior, which range from suicide in humans[1,2,3,4] to mating in animals.[5,6] The monoamines dopamine (DA) and serotonin (5-HT) have pivotal roles in human behavior. 5-HT regulates a plethora of behavioral, cognitive and physiological functions, such as mood, aggression, reward, sexuality, attention, memory and perception;[7,8] DA mediates a diverse list of neuroendocrine, behavioral and neurophysiological actions.[9]
No seasonal patterns in mood symptoms were detected (Supplementary Methods). 5-hydroxyindoleacetic acid (5-HIAA) seasonality correlated positively with total Beck Depression Inventory II (BDI-II) scores (Spearman’s rho 1⁄4 0.13, P 1⁄4 0.018), whereas cerebrospinal fluid (CSF) 5-HIAA did not correlate with BDI-II scores (Spearman’s rho 1⁄4 0.04, P 1⁄4 0.45). In this 3-year study of CSF monoamine turnover (N 1⁄4 479), we confirm that 5-HIAA concentrations fit a cosine model that displays a peak in spring and a trough in fall
We show that a significant proportion of the variance (5.4%) in 5-HIAA concentrations is explained by seasonality
Summary
Seasonal variation in monoaminergic transmission may be one of the mechanisms explaining circannual fluctuations in behavior, which range from suicide in humans[1,2,3,4] to mating in animals.[5,6] The monoamines dopamine (DA) and serotonin (5-HT) have pivotal roles in human behavior. 5-HT regulates a plethora of behavioral, cognitive and physiological functions, such as mood, aggression, reward, sexuality, attention, memory and perception;[7,8] DA mediates a diverse list of neuroendocrine, behavioral and neurophysiological actions.[9]. Seasonal variation in monoaminergic transmission may be one of the mechanisms explaining circannual fluctuations in behavior, which range from suicide in humans[1,2,3,4] to mating in animals.[5,6] The monoamines dopamine (DA) and serotonin (5-HT) have pivotal roles in human behavior. It has not been unequivocally determined whether and to what degree seasonal factors explain variation in monoaminergic transmission
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