Introduction

Since deaths attributed to sudden infant death syndrome (SIDS) occur during sleep, failure to arouse in a stressful situation comprises one component in the proposed mechanism of death. While the infant was previously apparently healthy, the hypothesis underpinning neuropathological studies is that an underlying defect in the infant's brain has contributed to death. The defect in infants who do not arouse may be developmental, inherited, or secondary to previous non-fatal insults. The brainstem and hypothalamus are two regions housing nuclei with important roles in stress responses and arousal mechanisms. This chapter focuses on studies of the hypothalamus and how deficits in this region may contribute to SIDS.

The hypothalamus is a small but complex part of the brain with important roles in the homeostasis of energy balance, circadian rhythms, and stress responses, as well as growth and reproductive behaviors (1). As a regulatory center for so many functions, it receives input from, and transmits output to, a large number of other brain regions. Thus, as the hypothalamus controls many physiological functions, and is highly interconnected with other brain regions, it is an excellent candidate for abnormalities contributing to the pathogenesis of SIDS.

The hypothalamus was evaluated early in the 1990s in SIDS infants (2, 3). At that time, fewer neurotransmitters had been identified compared to today. But even without our current understanding (e.g. of the orexins which were discovered in 1998), the hypothalamus was of interest in SIDS because of its known role in the regulation of sleep. Findings at that time included increased tryptophan content and decreased serotonin, increased serotonin receptor binding, and increased monoamine oxidase-A (MOA) activity, with decreased choline acetyltransferase (ChAT) activity (2) (see Table 28.1).

Updating our knowledge of the hypothalamus and its potential role in SIDS is important, because our understanding of the hypothalamus is now more sophisticated with regards to its structure, functions, and development (1). In addition, a series of recent studies have made important advances in our understanding of abnormalities in the hypothalamus of SIDS infants.