Preeclampsia, Placental Growth Factor, ADHD and Autism.

The underlying causes of neurodevelopmental conditions, such as Attention Deficit Hyperactivity Disorder (ADHD) and autism, remain to be fully discovered. Some are known. For example, genes are known to be strongly involved in both conditions. Concordance rate in twins is the likelihood that both twins will manifest the same disorder. In identical twins, who share virtually the exact same genome, the concordance rate for ADHD is 60% to 80%. Whereas the concordance rate for fraternal twins, who share 50% of their genome, is 30% to 40%. The concordance rates for autism in identical twins is 60% to 90%, and for fraternal twins about 10% to 30%.  However, in no case is concordance is 100%. Thus, for both of those conditions, genes play a major role but other factors are also involved.

Recent studies have shown that a factor that can play a role in both ADHD and autism is the emergence of preeclampsia in pregnancy. Preeclampsia is a condition of pregnancy that involves the health of the placenta, how that placental insufficiency affects the fetus, and subsequently how stress signals from the placenta affect maternal physiology.  Preeclampsia begins in the placenta, which is fetal and not maternal tissue. In early embryonic development, the placenta normally invades the uterine tissue and alters the architecture of the uterine blood vessels to commandeer an adequate supply of oxygen and nutrients. However, in preeclampsia this commandeering of uterine vessels is insufficient and the fetus suffers. Part of the reason why preeclampsia is associated with increased risk for both ADHD and autism may be low oxygen levels, inflammatory responses, oxidative stress, failure to generate blood vessel development, and immune factors occurring in the fetus.  As pregnancy progresses, an insufficient supply of oxygen and nutrients leads the placental tissue to produce various inflammatory substances that cross the placenta into maternal blood circulation. These inflammatory substances produce what become recognized as the maternal symptoms of preeclampsia, which include high blood pressure, edema, and eventually damage to organs such as the kidneys and liver. Preeclampsia also triggers a powerful systemic stress response in the mother, and this stress response then directly and indirectly impacts fetal development. When serious symptoms emerge in the mother,  which are also reflected in the baby, the treatment is to deliver the baby and the placenta as soon as possible.

One of the causes of placental insufficiency is a lack of a protein messenger called Placental Growth Factor, or PGF. Placental Growth Factor, as the name suggests, is found in the placenta of mammals and facilitates the embedding of placental tissue and vasculature into the uterine wall. However, like many such proteins and peptides in the body, its name is derived from what it was first discovered to do. In fact, PGF serves many roles in physiology, including roles that have little to do with the placenta. The protein is found in various parts of the human body, including non-pregnant females as well as males. A major role, which it utilizes in its effects on the placenta and uterus, is stimulation of angiogenesis. Angiogenesis is the growth and development of blood vessels. Thus, PGF plays an important role in wound healing. Perhaps surprisingly, PGF is also found in the brain. During embryonic development, PGF is expressed by neurons and the lining of blood vessels in brain tissue to guide cerebral angiogenesis as well as the placement of neurons and how they extend themselves into surrounding brain tissue.  It may also serve as a neurotrophic factor, that is, a stimulator of growth and development of neurons. Thus abnormalities in PGF in the fetal brain might be expected to have adverse neurodevelopmental effects.

A new study, published in JAMA Psychiatry, has confirmed that low levels of PGF in maternal blood, a key indicator of preeclampsia, are strongly associated with the likelihood of ADHD. However, whereas low PGF is seen in both fetal and maternal blood in preeclampsia, the association of low maternal PGF and ADHD was still seen even when preeclampsia did not emerge. Thus, a low level of PGF in the fetus may in itself be a factor in ADHD. On the other hand, whereas preeclampsia can clearly be a factor in autism, autism is generally associated with high levels of maternal PGF. It has been suggested that neurotrophic effects of high levels of fetal PGF may contribute to the apparent failure to prune unnecessary, redundant neurons from layers of the cortex  that is typical of autism. These findings suggest that PGF and preeclampsia can contribute independently to both ADHD and autism. Of note, while maternal and fetal levels of PGF are low in preeclampsia that occurs before the 34 week of gestation, these levels can remain normal when preeclampsia begins after that time.  Thus, many combinations of effects are possible.

Abnormal levels of PGF may also be involved in other neuropsychiatric conditions.  Vascular dysfunction and impaired neuroplasticity are increasingly recognized as factors  in the pathophysiology of depression. Studies profiling growth factors in patients with treatment-resistant depression have identified altered levels of PGF and other vascular and neurotrophic factors in the blood. Interestingly, Major Depression during pregnancy is correlated with low serum PGF during her pregnancy as well as with increased risk of preeclampsia and, in turn, ADHD and autism.  

The causes of ADHD and autism are complex. They are polygenetic and multifactorial. Current  political intrigue wants us believe that virtually nothing is known and nothing is being done to remedy that situation. False claims are made about things such as vaccines, which do not cause autism. Even worse are the cries that the “Truth” is known but being hidden by Big Pharma and Big Medicine. In fact, research into the causes of neurodevelopmental conditions such as ADHD and autism has been going on for years and continues at a quickened pace. A great deal has been learned, and very sophisticated methods are being used to learn more. We are getting answers.