A study published in the Archives of General Psychiatry shows that children of women who experience the death of a close relative may have an increased risk of developing schizophrenia later in life.  This study was conducted with records of children born in Denmark between 1973 and 1995, which were then linked to the central registry containing inpatient and outpatient treatment records. It consisted of 1.38 million individuals, including 21,978 children whose mothers experienced death of a close relative during the pregnancy, and 14,206 children of mothers who experienced illness of a close relative during the pregnancy.

Children of mothers who lost a close relative during the first trimester of pregnancy were 70% more likely to develop schizophrenia than those whose mothers were not exposed to the same loss during the 6 months before or during the pregnancy. Interestingly, this higher risk in the context of the loss of a close relative was found only for mothers without a family history of mental illness. For mothers with a history of the mental illness in the family, there was no evidence that exposure to death in the first trimester increased the risk of schizophrenia.

Despite the large cohort, the study’s limitations include the small number of cases of schizophrenia among the population, the inability to reach all mothers’ relatives, and the inability to examine gender differences in risk of schizophrenia. The study also did not take into the account possible confounding factors such as the mother’s socioeconomic status.

It will be important for future studies to attempt to define the biological basis for the increased risk of schizophrenia in the context of such loss, and to also elucidate any protective factors. Currently, we know that very early in pregnancy the fetal brain is especially vulnerable to stress hormones. In contrast, later in the pregnancy, maternal stress responses are blunted with different mechanisms such as the increased breakdown of the maternal stress hormone (glucocorticoid) and an increase in a protein that binds and inactivates maternal stress hormone (corticotropin releasing hormone, which stimulates glucocorticoid production). A recent Nature Genetics study included 152 individuals with schizophrenia whose parents did not have the disease. After comparing DNA of the children and their parents, it was found that approximately 10 percent of the offspring group had extra or missing copies of genes in sections of their chromosomes.  It remains to be clarified if these changes occurred in utero or after delivery.

Snezana Milanovic, MD, MSc

Khashan AS, Abel KM, McNamee R, Pedersen MG, Webb RT, Baker PN, Kenny LC, Mortensen PB. Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Arch Gen Psychiatry. 2008 Feb;65(2):146-52.

Xu B, Roos JL, Levy S, van Rensburg EJ, Gogos JA, Karayiorgou M. Strong association of de novo copy number mutations with sporadic schizophrenia. Nat Genet. 2008 May 30.

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