Elsevier

Medical Hypotheses

Volume 74, Issue 5, May 2010, Pages 880-883
Medical Hypotheses

Serotonin, pregnancy and increased autism prevalence: Is there a link?

https://doi.org/10.1016/j.mehy.2009.11.015Get rights and content

Summary

The prevalence of autism, a neurodevelopmental condition resulting from genetic and environmental causes, has increased dramatically during the last decade. Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo–pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation.

Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD.

Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. In this paper, we hypothesize that increased serotonemia during pregnancy, including due to SSRI intake, could be one of the causes of the raising prevalence in autism. If our hypothesis is confirmed, it will not only shed light on one of the possible reason for autism prevalence, but also offer new preventive and treatment options.

Introduction

Autism spectrum disorder (ASD) is a behaviorally defined neurodevelopmental disorder affecting as many as 1 in 150 children prevention [1], or even 1:91 according to the latest report of National Survey of Children’s Health [2]. Its defining features include mild to severe impairments in communication and reciprocal social interaction, as well as repetitive and stereotyped behaviors.

Reports of autism prevalence have increased dramatically during the past decade. This may be partly due to increased awareness of ASD resulting in more diagnoses being made, but also to environmental factors [3], [4]. Not much is known yet on the possible effect of certain drugs, food or environmental conditions on ASD progression.

Section snippets

DHS model of autism

There is evidence that otr (coding for oxytocin, OT) and avpr (coding for vasopressin) genes may be abnormal in some ASD individuals (for review, see [5]). However, decreased levels of OT could also be the consequence of abnormal levels of serotonin (5HT) during brain development.

The developmental hyperserotonemia (DHS) model of autism was first hypothesized by Patricia Whitaker-Azmitia (reviewed in [6]), who based her theory on the observation that high levels of serotonin is seen in the blood

Increased serotonin during pregnancy

In humans, increased levels of serotonin during pregnancy could have several distinct etiologies, including increased internal release, increased intake and decreased metabolism. As mentioned above, it is known that first-degree relative hyperserotonemia increases the risk of autism [13], [14], [15].

Drugs that release 5HT, such as cocaine, have been shown to dramatically increase the prevalence of autism, with 11.4% of children exposed in utero being affected [25]. However, in the light of

SSRIs and autism – is there a link?

Prozac was introduced in the USA in 1987. SSRIs are the third most prescribed antidepressant [26], with over 22.2 million prescriptions in the US in 2007. SSRIs are not contraindicated during pregnancy, and as high as 2.3% of mothers report using SSRIs from one month before to 3 months after conception [27], [28], [29].

Several studies have examined the teratogenic effects of SSRIs [30], [31], and some have concluded to an association with slightly increased risks of cardiac abnormalities. Those

Evidence supporting the DHS model of autism

In line with the DHS model, decreased levels/activity of serotonin have been described in ASD brains: PET studies have revealed decreased activity of radiolabeled serotonin in the frontal cortex and thalamus [34] and decreased serotonin synthesis [35] in autistic children, and a recent SPECT study has shown lowered serotonin binding potential in several brain areas in Asperger individuals, including the superior temporal cortex [36].

In addition, it is known that drugs that increase serotonin

Effects of hyperserotonemia on oxytocin

Oxytocin (OT) is a nanopeptide produced in the magnocellular neurosecretory cells in the supraoptic nucleus and the paraventricular nucleus (PVN) of the hypothalamus. It is released into the blood from the posterior lobe of the hypophysis, as well as directly from the perikarya, dendrites or axon collaterals of magnocellular neurons. OT fibers have endings in a variety of different brain areas, including the thalamus, the hippocampus, the amygdala, the pineal gland and the cerebellum [42].

OT is

Effects of hyperserotonemia on the amygdala

The amygdala plays an important role in the perception of emotion, and there are indications from several neuropathology, lesion and neuroimaging studies that it plays a role in the social cognition deficits in autism. Altered connections between the amygdala and other components of the emotional processing network could lead to an aberrant emotional response. Several anatomical studies have found abnormalities in the amygdala of autistic subjects, although their results do not allow any

Significance

The dramatic rise in autism prevalence may not only be due to an increased awareness and broader definition, but also to some factors in the environment. Among these factors, an elevated level of serotonin during pregnancy could play an adverse role in brain development. Elevated serotonin could be caused by intake of drugs elevating serotonin levels, and by the consumption of foods rich in serotonin. If our hypotheses are confirmed, our data would have consequences not only in our

Conflicts of interest statement

None declared.

Acknowledgments

This work was supported by the Swiss National Foundation Grant PP00B-110741 to NH.

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