Fetal Effects of Psychoactive Drugs

Abstract

There has been a longstanding concern with the fetal effects of psychoactive drug use by pregnant women. In this article we describe the effects of three drugs with similar molecular targets that involve monoaminergic transmitter systems. These stimulants include the illegal drugs cocaine and methamphetamine and the class of selective serotonin re-uptake inhibitors (SSRIs) used to treat maternal depression during pregnancy. We discuss the mechanisms of action of each drug, including a possible common epigenetic mechanism for their effects on the developing child. We also discuss fetal neurobehavioral techniques that may be useful in the early detection of the effects of in utero drug exposure.In the past three decades, the concept of behavioral teratology 1 expanded the field of teratology to examine behavioral effects in the neonate due to acute exposure to substances in utero, including environmental, nutritional, and drug exposures. 2,3 The developmental consequences of prenatal exposure to a toxic substance may include central nervous system (CNS) insult related to the period during gestation of the exposure. In contrast to the effects of drugs on the adult brain, which result in deformation of the developed brain, fetal effects are more likely to produce malformation in which the developing brain is prevented from forming normally. 4 The effects of exposure during the first half of gestation will impact processes related to cytogenesis and histogenesis whereas effects during the second half of gestation relate to brain growth and differentiation. During this organizational phase in the second half of gestation, progressive events (neuroblast proliferation and migration, axonal projection, and Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Recent years have seen further expansion of the principles of behavioral teratology to examine exposure effects on the human fetus at the time of the exposure. Epigenetic and organismic models of developmental theory suggest that true understanding of a developing system can occur with the study of its organization of form and structure as it moves toward a teleological state. 5,6 This study includes examination of the mutual influences of genes, physiology, and behavior as well as the physical, cultural, and social environments of the organism. 6 NIH Public AccessIncreasing evidence from preclinical, prospective clinical and epidemiological studies suggests that many biological factors acting during prenatal life are associated with adult disease as well as long term neurobehavioral abnormalities 7-17 and behavioral disorders. [18...

Cortisol Reactivity in Two-Year-Old Children Prenatally Exposed to Methamphetamine

“…Last, PME causes a downregulation of the placental norepinephrine transporter and 11β-hydroxysteroid dehydrogenase-2, which protect the fetus against the excess catecholamines and glucocorticoids. Consequent cortisol overexposure can adversely affect the programming of the HPA axis (Salisbury et al, 2009). Therefore, the observed increased cortisol reactivity to a stressful task among children in this study is in line with the suggested effects PME has on the fetus's HPA-axis programming.…”

“…The fi ndings fi rst support the hypothesis that PME may relate to alterations in the function of the HPA axis (Salisbury et al, 2009). Because methamphetamine is a stimulant of the sympathetic nervous system, prenatal exposure can cause increased synaptic concentrations of dopamine, serotonin, and norepinephrine.…”

“…This phenomenon has been referred to as the allostatic load, or the toll the body pays when adapting to sustained psychosocial or physical stress (McEwen, 1998). Consistent with known effects of stimulant drugs on the HPA axis (Salisbury et al, 2009) and the toxic-stress (Shonkoff et al, 2009) and allostatic-load (McEwen, 1998) theories, our results imply that elevated PME may be associated with alterations in the programming of the HPA axis refl ecting hyperactivity, which under signifi cant and chronic environmental stress then may become hypoactive.…”

“…Children with prenatal methamphetamine exposure (PME) are at an increased risk for alterations in neural growth and connectivity and consequent neurobehavioral defi cits (Salisbury et al, 2009). Unlike cocaine, another stimulant of the sympathetic nervous system, methamphetamine has a greater neurotoxic effect because of its longer half-life and direct transport into the cell .…”

“…Neuroimaging studies of children with PME indicate volume reduction in cortical and subcortical brain structures . In addition, adverse dose-response neurobehavioral effects, suggestive of alterations in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, have been reported among children with PME (Salisbury et al, 2009). Specifi cally, in the fi rst 5 days of life PME is linked to decreased arousal, increased stress, lethargy, and poor movement quality (Smith et al, 2008); long-term neurobehavioral defi cits include poorer motor performance among most heavily exposed 3 year olds (Smith et al, 2011) and poorer visual tasks performance, delayed verbal memory, and lower full-scale intelligence quotient scores in 7-and 15-year-olds (Roussotte et al, 2010).…”