Family History Plus Depression in Pregnancy May Up Schizophrenia Risk in Offspring

Pauline Anderson

October 22, 2009

October 22, 2009 — Depression during pregnancy by itself does not increase the risk for schizophrenia in offspring, but it does increase the risk when there is also a family history of psychosis, a new study suggests.

The study showed that the risk for schizophrenia in offspring is increased more than 14-fold when the mother suffers depression during pregnancy and the father has a history of psychosis.

"We found that maternal depressed mood did not increase the risk for schizophrenia, but in those offspring vulnerable to psychosis due to family history, maternal antenatal depression did increase the risk," said the study's lead author, Pirjo Maki, MD, PhD, senior lecturer, Department of Psychiatry, Institute of Clinical Medicine, University of Oulu, Finland. "So we can conclude that mother's antenatal depression may act as an additive risk factor; it increases the risk only when you have the genetic vulnerability already."

To reduce this risk, background factors, including familial risk for psychosis, could be explored thoroughly in pregnant women who are depressed, she said.

The study was published online October 15 in the American Journal of Psychiatry.

The researchers looked at the incidence of schizophrenia among children born in the northern Finnish provinces of Lapland and Oulu during 1966. They followed-up this cohort, which originally included 12,058 babies born alive, until 2001, when participants were 35 years old.

Depressed Mood in Pregnancy

The mothers of the study cohort were asked during pregnancy, mainly between 24 and 28 weeks' gestation, about their depressed mood. Almost 14% rated themselves as depressed or very depressed.

To assess familial risk for psychosis, researchers used the Finnish Hospital Discharge Register. They determined the incidence of psychosis among mothers and fathers from 1972, when the register was created, until 1997.

The researchers used the same register to identify offspring who were hospitalized because of a mental disorder. They scrutinized all case records, validated diagnoses for the Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, Revised, criteria and eventually identified 111 cases of schizophrenia and 45 cases of other psychoses.

The cumulative incidence of schizophrenia was 0.9% among children of nondepressed mothers and 1.3% among offspring of mothers with antenatal depressed mood.

Parental Psychosis

Of the offspring with parental psychosis, 3.3% had schizophrenia compared with 0.9% of those without a psychotic parent (adjusted odds ratio [OR], 3.9.). Fifteen (14.0%) of the 107 schizophrenia patients had a history of psychosis in 1 or both parents.

Among offspring of mothers with depressed mood during pregnancy, the risk for schizophrenia was significantly higher when there was a history of psychosis in a parent (adjusted OR, 9.4) than in those with a depressed mother but without parental psychosis (adjusted OR, 1.0) or those without maternal depression and with a psychotic parent (OR, 2.6).

The combination of the father having psychosis and the mother having depression antenatally resulted in the highest risk for schizophrenia (OR, 14.2).

Gene–Environment Interaction

One interpretation of these results is that they reflect an interaction of genes (a family history of psychosis) and environment (exposure to antenatal depression). It is possible that some of the effect of genes on the occurrence of schizophrenia is mediated through other environmental risk factors such as complications of birth and pregnancy and a dysfunctional early family environment, noted the authors.

Just how depression increases schizophrenia risk is not entirely clear. It may affect the hypothalamic-pituitary-adrenal axis and result in oversecretion of glucocorticoids in the fetus, which may disturb brain development. Exposure to maternal stress may also lead to dopaminergic hypersensitivity, which is linked to psychosis, said Dr. Maki.

The effect of maternal depression on babies continues after birth and may affect maternal–infant attachment, she added. Depressed mothers may be neglectful toward their baby, and this may disturb the child's emotional development.

Maternal depression is common during both pregnancy and the postnatal period, affecting up to 15% of mothers.

Gene–Gene Interaction

An alternative interpretation of the association between maternal depression and schizophrenia in offspring is that it is a gene–gene interaction. "It may be that genes predisposing to depression together with genes predisposing to schizophrenia have an additive effect on the vulnerability to psychosis," wrote the authors.

In light of these findings, physicians in maternity clinics could consider asking pregnant women about their frame of mind, and if the women are depressed, the physicians should explore background factors, including family risk for psychosis, said Dr. Maki. "Interventions and care to help the mother and her family should be offered."

Untreated Depression a "Tragedy"

Asked to comment on the study, Jennifer L. Payne MD, PhD, codirector, Women's Mood Disorder Center, and assistant professor, psychiatry, Johns Hopkins Hospital, Baltimore, Maryland, said the study underlines the importance of treating depression during pregnancy.

"Psychiatric problems are often dismissed as kind of luxury problems that you don't need to treat during pregnancy, and yet there's a strong literature saying that, yes you actually probably should, and this study is yet another support for that," she said.

As with headaches and sleep problems, some physicians are reluctant to treat depression during pregnancy, something Dr. Payne calls "a tragedy." "The problem is, they don't really understand how severe psychiatric problems can be in terms of their impact on a developing fetus," she said.

Study author Peter B. Jones reports having received research grant support from GlaxoSmithKline, a speaker's honorarium from Eli Lilly, and is coinventor on a patent for methods for assessing psychiatric disorders. The other authors have disclosed no relevant financial relationships.

Am J Psychiatry. Published online October 15, 2009.


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