poor trophoblastic invasion

I called my mom earlier to ask her some questions from my autism assessment intake form. She reminded me that she had preeclampsia while she was pregnant with me, and she took some kind of medication for it. The drugs listed by Wikipedia are labetalol, an alpha/beta adrenergic antagonist, and methyldopa, an alpha-2 agonist that also inhibits aromatic amino acid hydroxylase (i.e., reduced dopamine/norepinephrine/serotonin synthesis). Drugs in utero are interesting, but the preeclampsia turned out to be significant once I started looking thing up:


Lo and behold, a small study reports autism-like changes in the brains of 7-10 year-old children whose mothers had preeclampsia:

RESULTS: Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia.
CONCLUSIONS:This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies.

There also seem to be cognitive changes:

Psychometric testing revealed an impairment in working memory among PE-F1s. Eye-tracking studies revealed numerous impairments among PE-F1s including additional saccades required to reach the target, poor endpoint accuracy, and slower reaction time. However, PE-F1s made faster saccades than controls, and fewer sequence errors in the memory-guided task. Our study provides a comprehensive assessment of cognitive function among PE-F1s. The development of PE may be seen as an early predictor of reduced cognitive function in children, specifically in working memory and oculomotor control.

In a rodent model, it looks like there are problems with hippocampal neurogenesis, which would go with depression and spatial learning impairments:

Here, we established a preeclampsia-like rat model induced using Nω-nitro-l-arginine methyl ester (l-NAME) to analyze the developmental and functional changes in brains of the offspring. Body and brain weights were decreased in the l-NAME group at postnatal day 0 (P0). However, there were no significant differences between the l-NAME and control groups in brain and body weights at P56. Upon further analysis, we detected a deficiency in neurogenesis, but not in apoptosis, which contributed to the smaller brains of the offspring in the l-NAME group at P0. Additionally, we observed an increase in gliogenesis to compensate for the brain weights of the offspring at P56. Although the weight and laminar structure of the brains were essentially normal at P56, spatial learning and memory were severely impaired. We also found that adult hippocampal neurogenesis was disrupted in the offspring from preeclampsia-like rats, which may explain the cognitive deficiency. Moreover, qRT-PCR revealed a reduced expression of neurogenesis-related genes in the offspring.

There’s also epidemiological data:

Recent cohort studies suggested an association between pre-eclampsia and ASD. In the Swedish, population-based, case-control study that included 1216 subjects with autism who were born between 1987 and 2002 and 6080 controls, preeclampsia was associated with 50% increased risk of an autism spectrum disorder (Buchmayer et al., 2009). A recent study from the California Department of Developmental Services that compared 517 ASD cases to 350 controls found that pre-eclampsia complicated the pregnancy of children with ASD more than twice as often as those of controls and the association was more robust in those pregnancies complicated by severe disease (Walker et al., 2015). Two cohort data showed increased prevalence of ASD among pre-eclamptic pregnancies. Analysis of 87,677 births between 1996 and 2002, of the South Carolina Medicaid program, found greater odds of ASD with (OR = 1.69) or without (OR = 1.85) controlling for birth weight (Mann et al., 2010). Analysis of 218,890 singleton live births in Alberta, Canada, between 1998 and 2004 also found greater odds of ASD (OR = 1.49; Burstyn et al., 2010). Compared to these studies there was no association between pre-eclampsia and ASD among 28,967 children born between 1995 and 2008 in Aberdeen city and district (Love et al., 2012). A meta-analysis of 85 studies of pre-, peri,- and neonatal hazards related to PDD, including autism, concluded that there was not enough data in order to determine risk for PDD (Guinchat et al., 2012).

On that note, CBD is like the best thing ever for my neurogenesis problem:

Cannabidiol (CBD), the main non-psychotomimetic component of the plant Cannabis sativa, exerts therapeutically promising effects on human mental health such as inhibition of psychosis, anxiety and depression. However, the mechanistic bases of CBD action are unclear. Here we investigate the potential involvement of hippocampal neurogenesis in the anxiolytic effect of CBD in mice subjected to 14 d chronic unpredictable stress (CUS). Repeated administration of CBD (30 mg/kg i.p., 2 h after each daily stressor) increased hippocampal progenitor proliferation and neurogenesis in wild-type mice. Ganciclovir administration to GFAP-thymidine kinase (GFAP-TK) transgenic mice, which express thymidine kinase in adult neural progenitor cells, abrogated CBD-induced hippocampal neurogenesis. CBD administration prevented the anxiogenic effect of CUS in wild type but not in GFAP-TK mice as evidenced in the novelty suppressed feeding test and the elevated plus maze. This anxiolytic effect of CBD involved the participation of the CB1 cannabinoid receptor, as CBD administration increased hippocampal anandamide levels and administration of the CB1-selective antagonist AM251 prevented CBD actions. Studies conducted with hippocampal progenitor cells in culture showed that CBD promotes progenitor proliferation and cell cycle progression and mimics the proliferative effect of CB1 and CB2 cannabinoid receptor activation. Moreover, antagonists of these two receptors or endocannabinoid depletion by fatty acid amide hydrolase overexpression prevented CBD-induced cell proliferation. These findings support that the anxiolytic effect of chronic CBD administration in stressed mice depends on its proneurogenic action in the adult hippocampus by facilitating endocannabinoid-mediated signalling.

That’s in addition to the 5-HT1A-mediated increase in oxytocin release and all sorts of other good things.

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