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To the Editor: Barbara Stanley, Ph.D., and colleagues (1) reported decreased concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in CSF in a cohort of aggressive and nonaggressive patients without the "potential confound" of suicidal behavior. However, the authors did not acknowledge the important potential confound of seasonal variation in both serotonin function and aggressive behavior. Significant seasonal variation in CSF 5-HIAA concentrations in healthy humans has been reported (2). A review of studies demonstrating significant seasonal variation in a variety of measures of serotonin function in humans has been published elsewhere (3). This fluctuation may underlie the seasonal variation seen in a number of psychiatric disorders and phenomena, including suicide. Notably, the prevalence of human aggression has been shown to vary significantly across seasons (4, 5).
Therefore, given that the role of seasonality in this study was not analyzed by the authors, their conclusions about possible links between CSF 5-HIAA concentrations and aggression may be premature. Seasonal differences in time of lumbar punctures could explain any group differences the authors found. A seasonal analysis could be accomplished by performing a two-way analysis of variance by using the presence of aggression and season as independent variables. Another approach would be to use season or even photoperiod as covariates in an analysis of covariance. Arguably, ample evidence now mandates that seasonality be controlled in all studies of serotonin function.
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