Prenatal infections and stress have been shown to increase the incidence of schizophrenia, affective disorders and autism (Huttunen & Niskanen, Reference Huttunen and Niskanen1978; Mednick et al. Reference Mednick, Machón, Huttunen and Bonnet1988; Machón et al. Reference Machón, Mednick and Huttunen1997; Cannon et al. Reference Cannon, Clarke and Cotter2014). All of these disorders are known be associated with impairments in social relations. We would like to propose a novel mechanism linking the prenatal response to stress and inflammation with the later development of psychiatric disorder.
According to the polyvagal theory (Porges, Reference Porges2007) the autonomic system consists of three parts – the phylogenetically oldest dorsal parasympathetic or vagal system, the sympathetic system and phylogenetically newest ventral vagal system. These three parts of the autonomic nervous system of mammals play different roles in the evolutionary stress responses in mammals. The myelinated neurons of the ventral vagal system function as a ‘brake’ for the ‘fight-flight’ activity of sympathetic nervous system. The unmyelinated dorsal vagal activity takes control if the ‘fight/flight’ behavior fails to protect the individual, resulting in defensive immobilization – the ‘freeze’ response.
The efferent pathways of the ventral vagal neurons in the nucleus ambiguus (situated in the medullary reticular formation) are known to innervate muscles of the face, eyelids, larynx, pharynx and middle ear. These regions regulate facial expression, vocal prosody and listening, all of which promote social engagement. Functionally, the ventral vagal system lowers the heart rate, dampens the hypothalamic–pituitary axis, promotes self-soothing behaviors and thus enables the individual to engage with other individuals (Mednick et al. Reference Mednick, Machón, Huttunen and Bonnet1988). In this way the extent of social engagement is dependent on the vagal brake provided by the efferent neurons of nucleus ambiguus.
Developmentally, the number of myelinated vagal fibers increases from 23 to 28 weeks of gestation until birth, when the number of fibers is comparable to those observed in adolescence (Sachis et al. Reference Sachis, Armstrong, Becker and Bryan1982).
Putting these lines of research together, it is proposed that prenatal infections and stress affect the development of myelinated neurons of the ventral vagal system and, by this mechanism, increase the sensitivity of children for traumatic experiences and their risk for major psychiatric disorder. This theory merits research as it could have significant public health implications, and would highlight the critical importance of ensuring adequate medical and psychosocial supports during the perinatal phase.
Acknowledgments
This perspective piece has been adapted from a previous Finnish publication authored by Professor Matti Huttunen (Respektiä ja rakkautta, ISBN 978-952-5718-76-8). PROMETHEUS kustannus Oy (ltd) have kindly agreed to grant the right to publish this adapted translation of the book. This piece has been published in honor of Sarnoff Mednick, with whom this idea was developed and discussed a few months before his sad death in April 2015.
Conflicts of Interest
M.H. has no conflicts of interest to disclose. S.M. has no conflicts of interest to disclose.
Ethical Standards
The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committee on human experimentation with the Helsinki Declaration of 1975, as revised in 2008.
Financial Supports
This paper received no specific grant from any funding agency, commercial or not-for-profit sectors.
