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Mental Health, Mental Health Care, Mental Illness, Public Health, Science, Women's Health

Could Depression Actually Begin In The Womb?


Can a person actually be born with a predisposition to depression? Thanks to a new research project, we may soon know the answer to that question. In a groundbreaking new study, researchers at the Medical University of Vienna are attempting to determine whether immune responses in pregnant women lead to a subsequent tendency for depression in their children.

There is already some evidence supporting that maternal infections during pregnancy can have an effect on the development of certain mental illnesses later in life — however, the extent to which this affects depression in particular is not yet known. Scientists are therefore now examining an animal model to analyze cellular and molecular processes that can lead to such a predisposition.

It is a frightening thought, but the scientific evidence is clear: Influences that an expectant mother is exposed to can have a negative effect on the child’s mental development. In fact, it is generally accepted that infections suffered by the mother during pregnancy can contribute to an increased likelihood for schizophrenia and autism in their children. As part of a three-year project of the Austrian Science Fund FWF, researchers led by Dr. Daniela Pollak, of the Department of Neurophysiology and Neuropharmacology at the Medical University of Vienna, are now investigating whether this also applies to depression.

Of Mice & Men

The first objective of the work on mice, which are used here as model organisms, is to determine whether depression-like behavior in children in later life can actually be caused by immune responses during pregnancy. “We are also interested in whether such an immune response is linked to a change in brain development and whether that is based on the inhibition of a specific growth factor,” said Dr. Pollak. “Moreover, we are analyzing the associated structural, anatomical, molecular and functional changes in the brain.”

The findings from such a project are likely to of great social and scientific importance. Mood disorders like depression are among the most prevalent and debilitating forms of mental illness — but too little is known today about the cellular and molecular processes that mediate them. According to Dr. Pollack, this is also one of the reasons why there are only a limited number of options for diagnosing and treating such disorders:

“There is no independent objective diagnostic tool, such as a biomarker, for depression. We are reliant on the co-occurrence of a cluster of symptoms as a criterion,” said Dr. Pollack. “The same situation applies to treatment – substances that interact with monoamines, which are specific neurotransmitters – are most frequently used. However, their impact was discovered purely by chance more than 50 years ago and treatment with these compounds is characterized by a delayed onset of therapeutic effect and a range of adverse side effects. For a large proportion of patients, these drugs are even completely ineffective.”

To help improve this situation, the scientist will spend the next three years examining the cellular and molecular processes that can lead to depression. However, research is also going one step further, said Dr. Pollack: “We will also look at the genetic aspects. It may be that certain genetic predispositions can be a factor in maternal immune responses during pregnancy, leading to a subsequently higher predisposition to depression. We will clarify this.”

Byproducts of Maternal Infection

The new research is based on the assumption that neurogenesis — the generation of neurons — in the adult hippocampus (a region of the brain) has an effect on the development of depression. The regeneration of neurons in adults actually follows the exact same pattern that it does during embryonic development, leading the researchers to consider that even during this embryonic stage of neurogenesis, the seeds could already be sown for subsequent depression. This is a consideration that is now being investigated.

Epidemiological studies suggest that prenatal exposure to different types of viral or bacterial infections may be associated with similar outcomes; i.e., an increased risk of mental illness disorders in the offspring. In the 1960s and 1970s, several studies showed an increase in the incidence of mental retardation in children born to mothers who were pregnant during the 1964 rubella epidemic. More recent studies, based on serological testing and clinical examination to determine rubella exposure during pregnancy, have provided further convincing support for association between maternal infection during pregnancy and the development of mental disorders in the offspring. The “1968 Hong Kong” influenza epidemic is another example of an exposure that, for women pregnant at the time, increased the risk of their children developing mental illness in later life—schizophrenia especially—with second trimester exposure being of particular significance. Studies have also found an increased risk in children born to mothers where herpes simplex virus type 2 and toxoplasmosis were detected during pregnancy. Epidemiological studies have also found that prenatal exposure to poliovirus, measles, varicella-zoster, and maternal genital and reproductive infections are all associated with an increased incidence of mental illness in the child in later life.

Since infections arising from various causes have similar debilitating effects in later life, it appears that the exact pathogen may not be the critical factor in determining the neurological and cognitive outcome in the offspring. Instead, it is thought that response of the innate immune system, specifically the increased production of inflammatory cytokines, may be the critical mediator in altering fetal brain development and subsequently predisposing the offspring to mental disorders later in life. Inflammatory cytokines are essential for normal brain development. Factors such as the site of cytokine production, a change in balance between anti- and pro- inflammatory cytokines, placental transfer of cytokines, the effects of cytokines on glial cells, and the effects of glucocorticoids are important when evaluating the impact of maternal infection on fetal brain development.

While past studies have linked these processes to autism and schizophrenia, the three-year, FWF-supported project is the first comprehensive study of the effect of maternal infection during pregnancy on the onset of depression in later life. The researchers hope their findings will pave the way for new advances in both basic research in neuroscience and the identification of new treatment options for clinical depression.



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