Obstetric complications are probably one of the most oldest known complications suspected to be involved in the preconditioning of Schizophrenia. They seems to be more common in schizophrenia than in the general population (Cannon et al.) and it seems to be an higher risk to predisposed individuals that and obstetric events should occur (Schulze et al.) and that those patients who have suffered obstetric events often seems to have decreased volume of the hippocampus volume (Stefanis et al.). Such early environmental factors may impact on the development of the dopamine system. For example, hippocampal lesions made in neonatal rats result in increased striatal dopamine levels in post-pubertal rats. (Alquicer et al.) Animal studies indicate that perinatal damage leads to a labile dopaminergic system vulnerable to sensitization. (Moore et al) suggested that developmental disruption of the hippocampus cortex can result in dysregulation of the dopaminergic inputs to the striatum, increasing the response to novelty, mild stress,or psychotomimetics.
When Schmidt and Kastner did a systematic review of the functional enviromics they suggested that more than 50% of genes potentially associated with schizophrenia, particularly AKT1, BDNF, CAPON, CCKAR, CHRNA7, CNR1, COMT, DNTBP1, GAD1, GRM3, IL10, MLC1, NOTCH4, NRG1, NR4A2/NURR1, PRODH, RELN, RGS4, RTN4/NOGO and TNF, are subject to regulation by hypoxia and/or are expressed in the vasculature.
Finally there presence of Carbon Disulfide (CS2) in the exhaled breath from persons with schizophrenia is also a sign in itself since CS2 inhibits the carbonic anhydrase catalysis (CAC) which could make the slow reaction to hypoxia slower. Part 1 in the Hypo-Thesis of Schizophrenia is about CS2.
References
Cannon M, Jones PB, Murray RM (2002). Obstetric complications and schizophrenia: historical and meta-analytic review. American Journal of Psychiatry, 159, 1080–1092.
Nicodemus KK, Marenco S, Batten AJ, Vakkalanka R, Egan MF, Straub RE, Weinberger DR. (2008). Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 13:873–7.
Schmidt-Kastner R, van Os J, Steinbusch HWMS, Schmitz C. (2006). Gene regulation by hypoxia and the neurodevelopmental origin of schizophrenia. Schizophr Res 84:253–71.
Schulze K, McDonald C, Frangou S, Sham P, Grech A, Toulopoulou T, Walshe M, Sharma T, Sigmundsson T, Taylor M, Murray RM (2003). Hippocampal volume in familial and non-familial schizophrenic probands and their unaffected relatives. Biological Psychiatry, 53(7), 562–570.
Stefanis N, Frangou S, Yakeley J, Sharma T, O’connell P, Morgan K, Sigmundsson T, Taylor M, Murray RM (1999). Hippocampal volume reduction in schizophrenia: effects of genetic risk and pregnancy and birth complications. Biological Psychiatry, 46, 697–702.
