Within a mother’s body, the placenta is both a barrier and a chemical blockade behind which a fetus can safely develop into a whole and healthy baby. Yet, events that happen to the mother — such as a viral infection or psychological stress — can challenge and ultimately compromise the placental barrier and so impact the development of the fetus. For instance, the brain development of a fetus occurs as a sequence of timed and orderly events; if, though, the sequence is disrupted or slowed by a chemical onslaught, neurons may be “born” or migrate at the wrong moment and cause the brain to be "wired" in an atypical way.

It comes as no surprise, then, that scientists from Cardiff University have discovered evidence that suggests adults who were deprived of certain nutrients while developing in the womb may be more likely to suffer from poor mental health.

Experiment

To explore how imbalanced nutrients during fetal development might later affect adults, the researchers disrupted the balance of nutrients passing to mice in the womb and then examined the later behavior of the mice when they became adults. "We achieved this by damaging a hormone called Insulin-like growth factor-2, important for controlling growth in the womb,” said Dr Trevor Humby, a behavioural neuroscientist in the Schools of Psychology and Medicine, in a statement. “What we found when we did this was an imbalance in the supply of nutrients controlled by the placenta, and that this imbalance had major effects on how subjects were during adulthood – namely, that subject became more anxious later in life.”

The scientists plan further studies to investigate brain development, placental dysfunction, and the emotional state of adults. "The growth of a baby is a very complex process and there are lots of control mechanisms which make sure that the nutrients required by the baby to grow can be supplied by the mother," said Humby.

This thought has been echoed by other researchers, particularly two scientists in Maryland who investigated prenatal stress and its possible link to psychotic and depressive illnesses in adults.

Analysis

The researchers began with a rich understanding of the complexities of brain development: the birth of neurons, their migration to appropriate positions within the hemispheres, and their creation of a proper network of synaptic contacts happen predominantly during the prenatal period.

What exactly happens, though, when a fetus is exposed to environmental stressors that may alter this process of brain development?

To better understand the underlying mechanisms, the scientists analyzed cases where a pregnant mother’s immune system was activated or where she was exposed to psychological stress or malnutrition. An abundance of clinical literature already supports a link between such cases and neuropsychiatric illnesses in their offspring.

“The objectives here are to present recent preclinical studies of the impact of prenatal exposure to gestational stressors on the developing fetal brain and discuss their relevance to the neurobiological basis of mental illness,” wrote the authors.

Past studies, the authors stated, have associated schizophrenia with maternal infections, including rubella, measles, and influenza, during pregnancy. Yet, it is less clear whether maternal immune activation during a pregnancy may foster a mood disorder in offspring. Nevertheless, the common pathophysiological processes that occur when the mother’s immune system is responding to a virus, unpredictable psychological stress, or malnutrition appear to be linked to the symptoms of schizophrenia and psychosis. Such symptoms include sensorimotor gating, information processing, cognition, social function, and subcortical hyperdopaminergia.

“Depression-related phenotypes, such as learned helplessness or anxiety, are also observed in some model systems,” wrote the authors. “These changes appear to be mediated by the presence of proinflammatory cytokines and/or corticosteroids in the fetal compartment that alter the development the neuroanatomical substrates involved in these behaviors."

Cytokines are often described as molecules involved in cell signaling within the immune system; they may be a protein or peptide or another substance secreted by a cell that may affect the surrounding cells. A cytokine can be thought of as a spokesperson: it communicates for the cell, carrying signals locally among the cells. Proinflammatory cytokines, then, promote systemic inflammation, which is the body’s response to protecting itself against a pathogen. When the mother’s system, then, naturally responds to stress, infection, or lack of food, the molecules involved in that response will trespass the placental barrier and affect the brain development of a fetus.

“Environmental stressors during gestation can exert a major impact on brain development and thereby contribute to the pathogenesis of neuropsychiatric illnesses, such as depression and psychotic disorders including schizophrenia,” concluded the authors.

Sources: Mikaelsson MA, Constancia M, Dent CL, Wilkinson LS, Humby T. Placental programming of anxiety in adulthood revealed by Igf2-null models. Nature Communications. 2013.

Markham JA, Koenig JI. Prenatal stress: role in psychotic and depressive diseases. Psychopharmacology. 2011.