Abstract
Intrauterine or perinatal complications constitute a major risk for psychiatric diseases. Infants who suffered from hypoxia–ischemia (HI) are at twofold risk to develop schizophrenia in later life. Several animal models attempt to reproduce these complications to study the yet unknown steps between an insult in early life and outbreak of the disease decades later. However, it is very challenging to find the right type and severity of insult leading to a disease-like phenotype in the animal, but not causing necrosis and focal neurological deficits. By contrast, too mild, repetitive insults may even be protective via conditioning effects. Thus, it is not surprising that animal models of hypoxia lead to mixed results. To achieve clinically translatable findings, better protocols are urgently needed. Therefore, we compare widely used models of hypoxia and HI and propose future directions for the field.
Highlights
Schizophrenia (Sz) is a severe psychiatric disease affecting approximately 1% of world population
Perinatal HI models are valuable for Sz research, given a suitable model is employed to optimize specificity and construct validity, as many features of human patients can be mimicked
Severe HI models are more widely employed in neurology while mild chronic continuous or intermittent hypoxia models are more established in psychiatry because of the desired lack of cell death in the latter
Summary
Specialty section: This article was submitted to Schizophrenia, a section of the journal Frontiers in Psychiatry. Intrauterine or perinatal complications constitute a major risk for psychiatric diseases. Infants who suffered from hypoxia–ischemia (HI) are at twofold risk to develop schizophrenia in later life. Several animal models attempt to reproduce these complications to study the yet unknown steps between an insult in early life and outbreak of the disease decades later. It is very challenging to find the right type and severity of insult leading to a disease-like phenotype in the animal, but not causing necrosis and focal neurological deficits. It is not surprising that animal models of hypoxia lead to mixed results. We compare widely used models of hypoxia and HI and propose future directions for the field
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