Major threats to the developing brain

The trajectory of an individual’s developing brain is unique. The embryonic and new born brain is a complex product of the genes inherited from its parents and the environment encountered in utero.

Little can be changed about the genetic make-up of the developing brain. For instance, genetic abnormalities, like DiGeorge syndrome or Fragile X syndrome, frequently lead to early neurological and often later psychiatric conditions.

During pregnancy, a mother may also experience stressful events of varying severity, or a developing foetus exposed to prolonged hypoxia (lack of oxygen), toxins (foetal alcohol syndrome), viral or bacterial infections or nutritional deficits.

The placenta, to a large extent, can buffer the developing brain against such adversities, and the brain is good at adapting to challenges. However with more severe or prolonged exposures, these embryonic defences can become overwhelmed.

Vitamin D tablets spilling from a pill bottle on a table

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Photograph of a pregnant woman looking wistfully out the window

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There is strong epidemiological evidence linking insults to the developing brain during pregnancy – for example, when the expecting mother experiences stress, malnutrition, or exposure to toxins (e.g., alcohol) or disease-causing pathogens - to a higher risk of the child developing neurological or psychiatric disorders.

However, most children whose mothers experienced such insults do not develop such conditions. Nevertheless, unlikely does not mean impossible. So, what can impact a developing brain and how?

Stress

Stress, for example, due to emotionally difficult life events, as well as anxiety and depression experienced by a mother during pregnancy, affect the brain development of the unborn baby and increase its risk of developing behavioural, emotional, or cognitive problems, such as ADHD (attention deficit hyperactivity disorder), anxiety or depression, later in life. The exact mechanisms are still not fully understood, but changes in the mother’s balance of stress hormones, such as cortisol and glucocorticoids, with subsequent changes to the fetal environment, appear to play a role.

Nutritional deficiencies

Adequate nutrition during pregnancy and after birth is essential for healthy brain development. Periods of malnutrition have different negative effects depending on the period’s timing. For example, nutritional deficiencies during the second trimester of pregnancy result in a reduction in the number of neurons, whereas nutritional deficiency during the third trimester results in a reduction in the number of glial cells. It also matters which nutrients are deficient. For example, iron and certain vitamins, such as vitamin B9/folate and vitamin D, are particularly important.

Infections

Bacterial or viral infections can induce a cascade of inflammatory factors that can have profound effects on the function, connectivity and survival of developing neurons.

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Toxins

Certain drugs and other chemicals may damage developing neurons. Among the most common developmental neurotoxins is alcohol. Surprisingly, the damaging effects of alcohol on unborn babies and specifically their developing brains were first scientifically reported just 50 years ago. It is now well established that maternal alcohol consumption during pregnancy can cause severe, persisting developmental disorders, including cognitive impairment.

Oxidative damage

Every newborn faces a ‘hyperoxic challenge’ as it transitions from life inside the womb to self-sustained life outside. Under normal conditions, the newborn brain is well equipped to combat the damaging potential of oxygen radicals that form during this transition. Premature babies, however, are vulnerable to oxidative damage as their brains still have only low levels of antioxidants. Oxidative damage to the developing brain can cause several severe disorders, including epilepsy. The risk for it to occur is increased by factors that enhance the risk for premature birth, such as infection, alcohol or drug abuse, and age.

The role of the placenta

Although the developing brain is vulnerable to various threats, in a way, it has its guardian angel. The placenta acts as a protective barrier between mother and baby by keeping their bloodstreams separate. This way, few viruses and bacteria can infect the baby. The placenta is also effective at removing certain potentially harmful toxins. However, this is not completely failsafe.

Bit players: sex hormones and their influence

For some time now, scientists have known that certain psychiatric conditions are more common in one sex. For example, autism, attention deficit hyperactivity disorder and schizophrenia are more common in males, and depression and anxiety disorders are more common in females. The question is why.

The study of sex differences in psychiatric and neurodevelopmental disorders is complicated due to several interacting biological, psychological, and social factors. This may be compounded by a bias towards one sex in the diagnosis of certain disorders.

However, even controlling for such factors cannot fully account for the much higher incidence in one sex, such as that found in autism, which is four to five times more likely to be diagnosed in males.

The role that male and female sex steroids, such as testosterone and oestrogen, play in puberty is outwardly a process of physical transformation. Less appreciated is the effect these same hormones have on the developing brain. In primates, there is a surge of these hormones in the second trimester of pregnancy that appears to drive hormonal effects in the developing brain.

The effect of sex steroids on brain development has been extensively studied in lab rodents. In particular, neuron and immune cell numbers are quite different between male and female rodents in the hypothalamus and the cerebellum (brain regions involved in energy sensing and balance, respectively).

Indeed cross-talk between sex steroids and immune systems is emerging as a major research interest in how the brain develops. Timing is also critical as there are certain developmental ‘windows’ outside of which varying the sex hormone levels does not affect brain development and later behaviour.

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