The Development of Circadian Rhythms in Human Infants

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Summary 1. Normal thermoregulation is controlled by the hypothalamus. 2. Infants develop adult-like circadian rhythm core body temperature around 3 months of age. This is related to night time sleep. 3. Factors directly related to the infant, socio-economic factors as well as those related to infant care practices and the environment, affect the age of the maturation of temperature control. 4. Mature temperature circadian rhythms are stable from 3 months of age with a minimum drop to just below 36.5ºC unless the infant is ill or has been immunised. 18
1.6 Melatonin (Reviewed in Cardinal 1998) Melatonin is a primary chemical messenger of the internal „clock‟ which controls all physiological systems. It plays a key and central role in transmitting and translating messages regarding the external environment to the central nervous system which in turn allows circadian rhythms and peripheral oscillators to be synchronised. The infants‟ night time sleep was selected as the period for study in this project as it is during night time sleep that the evolution of circadian rhythms in infancy can be mapped. It is also during night time sleep that the predominance of cot deaths occurs (Blair et al., 2006), which is why it was originally chosen by this research group as its primary focus. 1.6.1 Production and Regulation of Melatonin Secretion Melatonin, a methoxyindole, is mainly made and secreted by the pineal gland during darkness. It is thought to be the primary messenger of the body which conveys messages regarding light and dark to cells in the body, specifically retinal cells in the eye. It helps stabilise circadian day and night rhythms and may determine patterns of physiological development. It is an important signal of the central biological clock. Melatonin is made from tryptophan and is found in circulating blood. Tryptophan is converted to 5-hydroxy tryptophan by hydroxylase enzyme. The product made as a result of this reaction is converted to serotonin. As a result of the action of two enzymes, namely sNAT and HIOMT, serotonin is converted to melatonin (Reiter, 1991, Vijayalaxmi Jr et al., 2002). Melatonin is not stored in the body. Therefore if 19
Page 1 and 2: The Development of Circadian Rhythm
Page 3 and 4: Table of Contents LIST OF FIGURES .
Page 5 and 6: 7.1 Analysis of infant sleep measur
Page 7 and 8: List of Figures Figure 1.1 - Diagra
Page 9 and 10: List of Tables Table 3.1 - Descript
Page 11 and 12: 1 Introduction Happiness is not a m
Page 13 and 14: Each of these independently is impo
Page 15 and 16: There is general agreement, that al
Page 17 and 18: Summary 1. Development encompasses
Page 19 and 20: Figure 1.1 - Diagram illustrating c
Page 21 and 22: A phase shift is used to describe a
Page 23 and 24: 1.4 Ontogeny in Human Infants Well
Page 25 and 26: 1.5.2 Circadian Rhythms in Temperat
Page 27: 1.5.4 Factors affecting Temperature
Page 31 and 32: mechanism by which this occurs is n
Page 33 and 34: It is at this time that infant slee
Page 35 and 36: 1.7 Cortisol Cortisol is a hormone,
Page 37 and 38: 1.7.3 Circadian pattern of Cortisol
Page 39 and 40: In a separate study, Weerth et al u
Page 41 and 42: Summary 1. Cortisol is crucial to a
Page 43 and 44: NREM sleep has 4 stages. It occupie
Page 45 and 46: 1.8.1 Functions of Sleep The functi
Page 47 and 48: 1.8.3 Ontogeny of Sleep in Infants
Page 49 and 50: Sleep can clearly be used as marker
Page 51 and 52: For the purpose of this study, the
Page 53 and 54: Summary 1. Sleep is defined by lack
Page 55 and 56: Overall the SCN generates signals (
Page 57 and 58: Figure 1.2 - The mammalian circadia
Page 59 and 60: 1.9.3 Molecular Components of the C
Page 61 and 62: Figure 1.3 - Mechanisms from SCN to
Page 63 and 64: 1.9.7 Melatonin and Clock Melatonin
Page 65 and 66: The links between the central clock
Page 67 and 68: Chapter 2 Methods
Page 69 and 70: There were strict inclusion and exc
Page 71 and 72: This personal contact on the postna
Page 73 and 74: 2.1.3 Home monitoring visits The fi
Page 75 and 76: 2.1.4 Further monitoring informatio
Page 77 and 78: Core body temperature was taken sim
Page 79 and 80:
2.3 Collection of urine samples Pai
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were read against air at 429 nm aft
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allowed the display and comprehensi
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2.8.1 RNA preparation and cDNA synt
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In total three methods were trialle
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2.11 Statistical methods For compar
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test that each infant‟s height an
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Power calculation Sample size: Fift
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3 Results 3.1 Recruited subjects an
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predominantly affluent areas of the
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Birth history and past medical hist
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3.1.3 Socioeconomic demographics of
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her best friend losing her battle w
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Sleep environment of infants All mo
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Summary 1. This study had higher ra
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4 Results 4.1 Core body temperature
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Degrees Celsius 36.70 36.60 36.50 3
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11-13 weeks There is no significant
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Core body temperature (degrees Cels
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Number of infants 10 8 6 4 2 0 7 8
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Mean minimum rectal temperature in
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Mean minimum rectal temperature in
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Figure 4.7 shows the changes in the
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Chapter 5 Result
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4 or 6 hourly samples. Circadian rh
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Figure 5.1 - Distribution of mean n
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5.1.2 Emergence of diurnal rhythm f
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Figure 5.3 - Histogram showing dist
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Figure 5.4 - Changes in night time
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Night-day difference in melatonin s
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Summary 1. There is an increase in
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6 Results DESCRIPTION OF THE URINAR
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Page 145 and 146:
6.1.2 Emergence of diurnal rhythm f
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Figure 6.3 - Histogram showing dist
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Page 151 and 152:
Cortisol values were corrected to a
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6.1.4 Relationship between night an
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Chapter 7 Results
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Mean Length of Sleep/ Wake Bouts Th
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Sleep parameters were recorded as m
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7.3 Development of infant sleep rel
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Figure 7.2 - Changes in infant slee
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Figure 7.4 - Changes in percentage
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Figure 7.5 - Changes in infant frag
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Figure 7.7 - Changes in number of m
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Figure 7.9 - Changes in the percent
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Sleep efficiency (%) 100.0 90.0 80.
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Chapter 8 Results
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Considering only those weeks of mea
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8.2 Description of peripheral gene
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18:30 hours 0.9927; 01:00 ours 1.01
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The weeks after temperature maturat
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Further peripheral gene graphical r
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Raw data points are represented by
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H3f3b/Gap H3f3b/Gap H3f3b/Gap H3f3b
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8.3 Detailed gene expression analys
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Summary 1. H3f3b was selected as ge
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9 Results FACTORS AFFECTING SLEEP A
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Care and infant related factors �
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Table 9.3 - Effect of family occupa
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* Class 7 used as reference group
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Table 9.6 - Effect of measured infa
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Summary: 1. A mature physiological
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10 Results 10.1 Circadian rhythms -
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value of above 0.5 for R squared wa
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Table 10.1 - Temporal relationship
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Chapter 11 Discussion
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� What if any are the factors whi
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11.1 Physiological development - ag
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There are other proven factors whic
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drawbacks of the spread of data - a
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presented in table 6.1 do not have
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separate methods were applied to th
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significant. Sleep latency was cons
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The function of sleep in developmen
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Melatonin secretion was higher on n
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In this study sleeping in the same
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Timing of sleep maturation was diff
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systematic, ordered developmental p
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individual gene plots that provide
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temperature recording devices adapt
Page 243 and 244:
Both melatonin and cortisol rhythms
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Extension of this period of monitor
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Second, we demonstrated the gene of
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Cortisol and melatonin Slope based
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Summary and Future work This study
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� Maximise technique for measurin
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“There is a science of infant car
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References
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Bajanowski, T., Vege, Å., Byard, R
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Chamley, C.A., Carson P, Randall D,
Page 263 and 264:
Frank, M.G., Heller, H.C., 2003. Th
Page 265 and 266:
intrahypothalamic administration of
Page 267 and 268:
Mirmiran, M. & Ariagno, R.L., 2000.
Page 269 and 270:
Rawson, D., Petersen, S.A., Wailoo,
Page 271 and 272:
Stokkan, K.A., Yamazaki, S., Tei, H
Page 273 and 274:
Winter, J.S.D., 1985. The adrenal c
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The Development of Circadian Rhythms in Human Infants

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