The argument between social determination and individual autonomy is highly debated in reference to neuropsychological disorders. Decades worth of literature have elucidated that the deficits in structural development responsible for these diseases are prone to environmental influence. That begs the question, are these malformations dependent solely on the infant's environment during child rearing, or could these changes be initiated prior to parturition? What role does their prenatal environment play in the infant's neurostructural development, and subsequently their susceptibility to neural diseases? Dr. Monsheel Sodhi addresses this question in co-authored research exploring how maternal restrictive stress caused a deficit of hippocampal RNA editing. These functional changes resulted in lower signs of behavioral interest among rats, suggesting that prenatal stress contributes to the reduced social interaction of offspring (Bristow et.al, 2021). Prenatal stress may take many forms, in this case, it is the physical entrapment of a pregnant dam within a restrictive space resulting in psychological distress. However, prenatal stress may also stem from intentional biological stressors induced by one’s actions, such as smoking. A 2018 meta-analysis reviewed comparative observational studies with the aim of finding the effects of prenatal maternal tobacco ingestion and to their surprise, “exposure to prenatal smoke increased the risk of schizophrenia by 29%” (Hunter, et.al, 2018). This expansion of research surrounding prenatal stress’s effect on the development of schizophrenia and similar neurophysiological diagnoses is essential for understanding and identifying the structural targets for novel psychopharmacological interventions.
Dr. Sodhi participated in research investigating the impact of stress on the glutamate system and RNA editing, with the aim of developing a drug targeting the negative symptoms of schizophrenia. In her presentation, she discussed how reduced social withdrawal is associated with glutamatergic systems. Glutamate transmission exhibits a parabolic relationship with cognition and mental abilities, meaning that both reduced and increased activity can damage the neural circuitry. She explained that prenatal stress might lead to deficits in RNA editing which is crucial for the transcription of adenosine deaminase enzymes. These proteins are responsible for purine metabolism, and further down the pathway, the functionality of the glutamatergic AMPA receptor. They conducted experiments measuring the RNA editing of 40 gene targets. After being subjected to prenatal stress, the mutant mice had increased social interaction compared to the wild-type cohort, showing similar behavior as the non-stressed mice. Additionally, mutant male mice had greater synaptic maturation, all of which demonstrate prospective targets for future psychopharmaceuticals.
Dr. Sodhi's research is centered around the effects of prenatal stress, and while this provides a well-structured understanding of the neurodevelopmental symptoms resulting from restrictive stress, a more comparable example is examined through Hunter et.al.’s Meta-analysis of prenatal tobacco exposure’s risk to the development of schizophrenia. Prenatal exposure to tobacco and nicotine has long-term consequences on neuronal functionality. Once maternally ingested, these substances can cross the placenta and bind to nicotinic acetylcholine receptors in the developing fetal brain. This can lead to reduced functionality of the postnatal dopaminergic system, a symptom strongly correlated with schizophrenia (Stathopoulou, et.al., 2013). Additionally, there is a likelihood of prenatal stress responses in the fetus, as evidenced by analysis of the altered hormone levels in cord blood. This could possibly exacerbate the dysfunctionality of the glutamatergic system, as explained by Dr. Sodhi's research. These effects could partially contribute to the fetus's risk of schizophrenia. As explained in Hunter et.al.’s Meta-analysis, exposure to prenatal smoke increases the risk of schizophrenia, as compared to participants without exposure (Hunter et.al, 2018).
These disruptions, from both restrictive prenatal stress and prenatal exposure to tobacco and nicotine, can lead to impaired synaptic plasticity in various neurotransmitter systems, such as the glutamatergic and dopaminergic pathways, respectively. It is important to understand the mechanisms behind these two processes so that psychopharmaceuticals can be developed targeting the protein products deficient in these systems. However, further research does need to be accomplished, specifically centered around clarifying the dose-response relationship between the level of prenatal exposure to tobacco or restrictive stress and the chance of schizophrenia. These findings can then work in a concerted manner, with the information being used to inform public health interventions directed toward reducing exposure to these stressors.
References
Stathopoulou, A., Beratis, I. N., & Beratis, S. (2013). Prenatal tobacco smoke exposure, risk of schizophrenia, and severity of positive/negative symptoms. Schizophrenia Research, 148(1-3), 105–110.
Harte, E. N., et al. (2021). Prenatal Restraint Stress Alters Hippocampal RNA Editing and Social Interaction Behavior in Adult Offspring: Reversal by Clozapine. bioRxiv.
Hunter, A., Murray, R., Asher, L., & Leonardi-Bee, J. (2020). The Effects of Tobacco Smoking, and Prenatal Tobacco Smoke Exposure, on Risk of Schizophrenia: A Systematic Review and Meta-Analysis. Nicotine & Tobacco Research, 22(1), 3–10.
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