Season of Sampling and Season of Birth Influence Serotonin Metabolite Levels in Human Cerebrospinal Fluid

BACKGROUND: Animal studies have revealed seasonal patterns in cerebrospinal fluid (CSF) monoamine (MA) turnover. In humans, no study had systematically assessed seasonal patterns in CSF MA turnover in a large set of healthy adults. METHODOLOGY/PRINCIPAL FINDINGS: Standardized amounts of CSF were prospectively collected from 223 healthy individuals undergoing spinal anesthesia for minor surgical procedures. The metabolites of serotonin (5-hydroxyindoleacetic acid, 5-HIAA), dopamine (homovanillic acid, HVA) and norepinephrine (3-methoxy-4-hydroxyphenylglycol, MPHG) were measured using high performance liquid chromatography (HPLC). Concentration measurements by sampling and birth dates were modeled using a non-linear quantile cosine function and locally weighted scatterplot smoothing (LOESS, span = 0.75). The cosine model showed a unimodal season of sampling 5-HIAA zenith in April and a nadir in October (p-value of the amplitude of the cosine = 0.00050), with predicted maximum (PC(max)) and minimum (PC(min)) concentrations of 173 and 108 nmol/L, respectively, implying a 60% increase from trough to peak. Season of birth showed a unimodal 5-HIAA zenith in May and a nadir in November (p = 0.00339; PC(max) = 172 and PC(min) = 126). The non-parametric LOESS showed a similar pattern to the cosine in both season of sampling and season of birth models, validating the cosine model. A final model including both sampling and birth months demonstrated that both sampling and birth seasons were independent predictors of 5-HIAA concentrations. CONCLUSION: In subjects without mental illness, 5-HT turnover shows circannual variation by season of sampling as well as season of birth, with peaks in spring and troughs in fall

Median concentrations of monoamine metabolites (in nmol/L) in cerebrospinal fluid with standard deviations (S.D.), per season (italics indicate totals).

<p>Median concentrations of monoamine metabolites (in nmol/L) in cerebrospinal fluid with standard deviations (S.D.), per season (italics indicate totals).</p

Median CSF 5-HAA Concentrations (in nmol/L) are plotted against Month of Birth.

<p>Bold line represents cosine, thin line represents LOESS and dashed lines represent 95% CIs of the cosine. Whiskers indicate 95% CIs of 5-HIAA concentrations.</p

Median CSF 5-HAA Concentrations (in nmol/L) are plotted against Month of CSF Sampling.

<p>Bold line represents cosine, thin line represents LOESS and dashed lines represent 95% CIs of the cosine. Whiskers indicate 95% CIs of 5-HIAA concentrations.</p

Amplitude of the best fitting models per metabolite with significance levels (in bold: Bonferroni-corrected significant results).

<p>T-statistic of the amplitudes, tmax (month during which levels peak), tmin (month during which levels are at their lowest), and best-fitting model based on deviance calculations. Feb = February; Nov = November; Sept = September; Dec = December.</p