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Prog Neuropsychopharmacol Biol Psychiatry. 2020 Mar 4;101:109910. doi: 10.1016/j.pnpbp.2020.109910. [Epub ahead of print]

Implications of early life stress on fetal metabolic programming of schizophrenia: A focus on epiphenomena underlying morbidity and early mortality.

Author information

1
Barcelona Clinic Schizophrenia Unit, Neuroscience Institute, Hospital Clinic, Barcelona, Spain; Institute of Biomedical Research Agusti Pi iSunyer (IDIBAPS), Barcelona, Spain; Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain; Department of Medicine, University of Barcelona, Barcelona, Spain. Electronic address: cgarcia3@clinic.cat.
2
Centre for Global Health, Trinity College Dublin, Dublin, Ireland; Department of Psychology, Trinity College Dublin, Dublin, Ireland; School of Medicine, Trinity College Dublin, Dublin, Ireland.

Abstract

The fetal origin of adult disease hypothesis postulates that a stressful in utero environment can have deleterious consequences on fetal programming, potentially leading to chronic disease in later life. Factors known to impact fetal programming include the timing, intensity, duration and nature of the external stressor during pregnancy. As such, dynamic modulation of fetal programming is heavily involved in shaping health throughout the life course, possibly by influencing metabolic parameters including insulin action, hypothalamic-pituitary-adrenal activity and immune function. The ability of prenatal insults to program adult disease is likely to occur as a result of reduced functional capacity in key organs-a "thrifty" phenotype-where more resources are re-allocated to preserve critical organs such as the brain. Notably, it has been postulated that the manifestation of neuropsychiatric disorders in individuals priorly exposed to prenatal stress may arise from the interaction between hereditary factors and the intrauterine environment, which together precipitate disease onset by disrupting the trajectory of normal brain development. In this review we discuss the evidence linking prenatal programming to neuropsychiatric disorders, mainly schizophrenia, via a "Thrifty psychiatric phenotype" concept. We start by outlining the conception of the thrifty psychiatric phenotype. Next, we discuss the convergence of potential mechanistic pathways through which prenatal insults may trigger epigenetic changes that contribute to the increased morbidity and early mortality observed in neuropsychiatric disorders. Finally, we touch on the public health importance of fetal programming for these disorders. We conclude by providing a brief outlook on the future of this evolving field of research.

KEYWORDS:

Barker hypothesis; Developmental origins of health and disease; Epigenetics; Fetal programming; Metabolism; Neuropsychiatric disease; Schizophrenia; Thrifty psychiatric phenotype

Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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