Prenatal stress: Role in psychotic and depressive diseases

Abstract

Rationale-The birth of neurons, their migration to appropriate positions in the brain, and their establishment of the proper synaptic contacts happen predominately during the prenatal period. Environmental stressors during gestation can exert a major impact on brain development and thereby contribute to the pathogenesis of neuropsychiatric illnesses, such as depression and psychotic disorders including schizophrenia.Objective-The objectives here are to present recent preclinical studies of the impact of prenatal exposure to gestational stressors on the developing fetal brain and discuss their relevance to the neurobiological basis of mental illness. The focus is on maternal immune activation, psychological stresses, and malnutrition, due to the abundant clinical literature supporting their role in the etiology of neuropsychiatric illnesses.Results-Prenatal maternal immune activation, viral infection, unpredictable psychological stress, and malnutrition all appear to foster the development of behavioral abnormalities in exposed offspring that may be relevant to the symptom domains of schizophrenia and psychosis, including sensorimotor gating, information processing, cognition, social function, and subcortical hyperdopaminergia. Depression-related phenotypes, such as learned helplessness or anxiety, are also observed in some model systems. These changes appear to be mediated by the presence of proinflammatory cytokines and/or corticosteroids in the fetal compartment that alter the development the neuroanatomical substrates involved in these behaviors.Conclusion-Prenatal exposure to environmental stressors alters the trajectory of brain development and can be used to generate animal preparations that may be informative in understanding the pathophysiological processes involved in several human neuropsychiatric disorders.

The rs11191580 variant of the NT5C2 gene is associated with schizophrenia and symptom severity in a South Chinese Han population: evidence from GWAS

“…Finally, although genetic effects are crucial to elucidating the cause of SCZ, non-genetic factors (such as prenatal stress, exposure to viruses during pregnancy, and social disorganization of neighborhoods) should not be ignored. [25][26][27] In conclusion, this study validated the association of the rs11191580 polymorphism within NT5C2 with SCZ susceptibility in a South Chinese Han population. Furthermore, this work is the first to report that GWAS-supported variant rs11191580 conferred negative and lack of response symptoms in SCZ.…”

Estudos traducionais de neuropsiquiatria e esquizofrenia: modelos animais genéticos e de neurodesenvolvimento

“…Neurodevelopmental animal models include maternal immune activation, prenatal malnutrition, the interruption of neurogenesis by methylazoxymethanol (MAM) and the neonatal ibotenic acid lesion of the ventral hippocampus 113,114 . Additional models are represented by the exposure of pregnant mice to unpredictable stress, maternal separation or birth complications [115][116][117] . All of these models have revealed behavioural deficits associated either with positive, cognitive or negative symptoms of schizophrenia, and alterations in the dopaminergic, glutamatergic, GABAergic and serotonergic systems [118][119][120][121][122][123][124] .…”

Placental programming of anxiety in adulthood revealed by Igf2-null models

“…Various programming stimuli, such as periods of foetal malnutrition, which result in intrauterine growth restriction (IUGR), are associated with heightened risk for metabolic and cardiovascular disease [3][4][5] . The long-term consequences of compromised gestation, as indexed by IUGR, also give rise to a range of psychiatric effects [6][7][8] , including increased risk for emotional disorders [9][10][11] . The biological mechanisms whereby events occurring before birth can influence emotionality later in life remain unknown.…”