Maturational changes in blood serotonin levels and platelet counts

Maturational changes in blood serotonin levels and platelet counts

Maturational Changes and in Platelet Blood Serotonin Levels Counts b~c have rcw3ltly tlcinonstratc~d that ct...

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Maturational

Changes and

in Platelet

Blood

Serotonin

Levels

Counts

b~c have rcw3ltly tlcinonstratc~d that ct
AGE,

BLOOD

SEROTONIN,

AND

91

PLATELETS

METHODS

Subjects. All control subjects were free of apparent illness both at the time of testing and during the period immediately preceding testing and none had a past history of major illness. Most were free from medication at the time of testing. A few were taking vitamin supplements or birth control pills, but the values obtained from these subjects were consistent with the others in their age groups and thus they were included in the data presented. The vast majority of subjects were Caucasian and no attempt was made to assess possible racial population differences. Data from males and females were coded and analyzed separately. A menstrual history was obtained from all females, which, for the sake of comparison, was normalized to a 30-day cycle and then divided into 5-day segments. The serotonin and platelet data reported are the means of the values within each 5-day period and on the lirst day of menses. All blood samples were drawn in the early morning to minimize possible diurnal influences, and before breakfast to eliminate possible effects of dietary intake. For some individuals consecutive samples were obtained on several different days. The means of these individual values were included in the maturational study while the separate values were used to assess intraindividual variability or changes accompanying the phases of the menstrual cycle. Assays. Whole blood serotonin values were determined ‘by the method of Yuwiler et al. (3). Samples were collected in vacuum tubes containing EDTA,? stored on ice, and all assays were begun within an hour of the time of blood collection. All blood samples were coded and were run on a blind basis. A blood sample from one of the investigators was included in each day’s experiment to assure day-to-day consistency in the assays. In some instances duplicate samples from the same individuals were included and their position randomized among the specimens. Blood platelet levels were determined by visual counting using the Rees-Ecker method (4). Duplicate, coded samples for platelets were run throughout. Statistical comparisons were carried out using a Student’s t test. A significance level of P < 0.05 was taken as the criterion for group differences. RESULTS

Male-Female Differences. Neither the means nor variances of the blood serotonin levels or platelet counts were significantly different between males and females within each age group. As a result, values for males and females were subsequently pooled for the maturational study. ‘Obtained

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Dickinson

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IN YEARS

FIG. 1. Maturational changes in blood serotonin levels. Normal subjects were divided in groups according to age at time of testing. Each point represents the mean value for the number of individuals indicated by the numeral above the point. The vertical lines extend for 1 SD above and below path point.

AGE,

BLOOD

SEROTONIN,

TABLE

AND

93

PLATELETS

1

INTRAINDIVIDUAL STABILITY OF BLOOD SEROTONIN LEVELS AND PLATELET COUNTS Age Subject Blood 1 2 3 4 5 6 7 Blood 1 2 3 4 5 6 7 8 9

Na serotonin

platelets

a Determinations nations.

(months)

(pg/ml) 4 4 3 3 3 18 5 X lO”/ml 4 4 3 3 3 23 3 3 5 were

made

Sex

Mean

Range

161 160 160 160 288 480 504

F F F F M M

M

0.155 0.192 0.117 0.099 0.201 0.108 0.195

0.141-0.162 0.145-o. 203 0.115-0.119 0.088-O. 109 0.199-0.204 0.090-0.129 0.190-O. 207

161 160 160 160 288 480 504 211 264

F F F F M M M M M

349 282 257 312 246 244 274 261 165

at least

1 week

apart.

SD

0.009 0.033 0.002 0.010 0.004 0.011 0.007

294-423 261-293 285-338 230-293 214-271 187-306 265-291 230-293 152-168 N is the number

54 15 7 26 29 34 14 31 9 of such

determi-

seen by the large variance at each age group. However, as seen in Table 1, values for a single individual were relatively constant over short periods of time. A similar maturational pattern was found for blood platelet counts (Fig. 2) which also declined between age 1 and puberty and then remained fairly constant. In both instances small secondary peaks have been superimposed upon the major trend, but the large variances and the relatively small number of subjects within each age group preclude any firm statement on this observation. DISCUSSION

Although there are several reports of maturational changes in platelet counts during the first year of life (7, 8)) very little data are available on platelet or serotonin changes during the subsequent period of childhood. Merritt and Davidson (7) reported an increase in blood platelet counts over the first year of life from a mean level of 277 X 106/ml (range 140-290) at birth to 330 X 10B/ml (250470) at 1 year of age. Our own data, using a somewhat different method on a considerably smaller sample, yield an average platelet level of 380 X 106/ml over the O-I-year period and a fall from that level over the subsequent 12-13

J

FIG. 3. Platelet and serotonin changes during the menstrual cycle. Individual cycles were normalized to a 30-day cycle and divided into five equal periods. Each point is the mean for the number of individuals indicated by the numerals above the points. The numbers at the top of the figure indicate 2 SD above and below the point. Day one is the first day of menses.

AGE,

BLOOD

SEROTONIN,

AND

PLATELETS

95

years, accompanied by a corresponding drop in blood serotonin levels. These results thus clearly demonstrate that age is an important parameter to be considered in studies on blood serotonin levels in childhood and that attempts to compare values from young patients with values from their older siblings or adults would tend to introduce serious distortions. For example, a comparison between the serotonin level of a mongoloid child and that of an adult would yield a smaller difference than a comparison between that patient and a normal child of the same age. The results also indicate a close, but not complete, parallel between maturational changes in blood serotonin levels and platelet counts. Since serotonin is stored in the platelets, this correspondence is not surprising and might only reflect a decreasing availability of storage sites with increasing age. It should be noted, however, that platelet storage capacity for serotonin is not necessarily a limiting factor. For example, it has been shown that platelet serotonin levels can be increased nearly lo-fold following intravenous infusion of serotonin (9). Serotonin/platelet ratios are significantly different from each other during some phases of the menstrual cycle, and some differences between individuals in serotoninlplatelet ratios are marked and unlikely to be due simply to measurement errors. Changes during the menstrual cycle may reflect differences in serotonin uptake by young or aged platelets. It has been demonstrated in dogs that platelet size varies with platelet age, young platelets being larger than older platelets (10). Further, it has been reported (11) that the relative proportion of young and old platelets changes over the course of the menstrual cycle, with older forms predominating before menses and younger forms predominating immediately after menses. Ovulation was noted to be accompanied by an abrupt decrease in young cells and an abrupt rise in mature forms. The rapidity of uptake and metabolism of serotonin by platelets of different ages is unknown but could be related to the present observations. The reasons for the changes in serotonin and platelet levels with age are obscure. Exercise is reported to induce thrombocytosis ( 12), but it is unlikely that differences in activity levels between prepubertal children and adults can fully account for the results in this study. Nor is it likely that these changes reflect some corresponding alteration in the distribution of young and aged platelets. Platelet half-life appears to be the same in normal children and adults (13). Whatever the mechanism, however, it is clear that recognition of these maturational changes is important for proper evaluation of the results of any studies involving serotonin levels and platelet counts.