Dysfunction of Maternal Thyroid Hormones and Psychiatric Symptoms (original) (raw)
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The regulation in the maternal hypothalamus-pituitary-thyroid axis (HPTA) displays vital actions during the development of CNS (development and differentiation of neurons, oligodendrocytes, astrocytes and microglial cells). In addition, the dysregulations in the activities of maternal THs (hypothyroidism or hyperthyroidism) may interrupt the development of CNS and cause persistent neural disorders, mental retardation, and several psychiatric symptoms. Hypothyroidism can cause several abnormalities as the following: (1) increase the levels of reactive oxygen species (ROS); (2) augmentation of phagocytosis; (3) elevate the activities of the proinflammatory markers such as interleukin-1β and macrophage inflammatory protein-1α; (4) decrease the activities of the antioxidant enzymes; (5) reduce the lymphocyte proliferation parameters; (6) diminish the cell migration and the production of antibody; and (7) decrease the immune response. As well, hyperthyroidism can reduce the activities of the proinflammatory markers such as monocytes and macrophages. Additional studies are required to elucidate the interactions between, thyroid dysfunctions, microglia, and neuropsychological disorders.
The regular activities of the maternal thyroid gland may be a controller of the developing CNS. As well, the alterations in maternal THs (hyperthyroidism or hypothyroidism) during the gestation may lead to permanent damage in the neonatal CNS and may cause mood disorders (neurological and mental diseases). The symptoms of mood disorders caused by thyrotoxicosis include restlessness, depression, anxiety, mania, and impaired concentration. These disorders can increase the loss of work productivity, and delay the cognitive and economic features. Hence, management of maternal thyroid and mood dysfunctions may reduce the risk of CNS complications. However, data on maternal thyroid diseases/thyroid autoimmunity disorders and neonatal mood dysfunctions are less conclusive and the association of these states to central TH function desires further examination. Also, the molecular actions of thyroid disorders on the mood behavior during the gestation and lactation periods are necessary.
Cerebral Cortex, 2010
Hypothyroxinemia affects 35--50% of neonates born prematurely (12% of births) and increases their risk of suffering neurodevelopmental alterations. We have developed an animal model to study the role of maternal thyroid hormones (THs) at the end of gestation on offspring's cerebral maturation. Pregnant rats were surgically thyroidectomized at embryonic day (E) 16 and infused with calcitonin and parathormone (late maternal hypothyroidism [LMH] rats). After birth, pups were nursed by normal rats. Pups born to LMH dams, thyroxine treated from E17 to postnatal day (P) 0, were also studied. In developing LMH pups, the cortical lamination was abnormal. At P40, heterotopic neurons were found in the subcortical white matter and in the hippocampal stratum oriens and alveus. The Zn-positive area of the stratum oriens of hippocampal CA3 was decreased by 41.5% showing altered mossy fibers' organization. LMH pups showed delayed learning in parallel to decreased phosphorylated cAMP response element-binding protein (pCREB) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) expression in the hippocampus. Thyroxine treatment of LMH dams reverted abnormalities. In conclusion, maternal THs are still essential for normal offspring's neurodevelopment even after onset of fetal thyroid function. Our data suggest that thyroxine treatment of premature neonates should be attempted to compensate for the interruption of the maternal supply.
Maternal thyroid hormones early in pregnancy and fetal brain development
Best Practice & Research Clinical Endocrinology & Metabolism, 2004
During the last few decades our understanding of the possible role of thyroid hormones during brain development has increased and contributed to resolve previously discordant hypotheses, although much remains to be clarified. Thyroid hormones of maternal origin are present in the fetal compartment, despite the very efficient uterine-placental 'barrier', necessary to avoid potentially toxic concentrations of free T4 and T3 from reaching fetal tissues before they are required for development. T3 remains low throughout pregnancy, whereas FT4 in fetal fluids increases rapidly to adult levels, and is determined by the maternal availability of T4. It is present in embryonic fluids 4 weeks after conception, with FT4 steadily increasing to biologically relevant values. T3, generated from T4 in the cerebral cortex, reaches adult values by mid-gestation and is partly bound to specific nuclear receptor isoforms. Iodothyronine deioidinases are important for the spatial and temporal regulation of T3 bioavailability, tailored to the differing and changing requirements of thyroid hormone-sensitive genes in different brain structures, but other regulatory mechanism(s) are likely to be involved. Maternal transfer constitutes a major fraction of fetal serum T4, even after onset of fetal thyroid secretion, and continues to have an important protective role in fetal neurodevelopment until birth.
The normal adequate of the maternal thyroid hormones (THs) is necessary for the fetal/neonatal brain development. The maternal thyroid dysfunctions (maternal hypothyroidism) during the gestation may cause several disorders in the neonatal cognitive and social behaviors. These effects might depend on the severity of thyroid disorders, sex type and developmental period. Females are more susceptible to developing internalizing problems while males are reliably more vulnerable to developing externalizing problems (biological or environmental risk factors). However, this link is weak and the fundamental mechanisms undistinguishable. Additional studies are necessary to examine whether the individual variations in THs trajectories (FT4 and TSH levels) during the gestation will be a better indicator of neonatal cognitive behavioral disorders than maternal THs levels evaluated at one trimester of pregnancy. In addition, several studies are warranted to examine whether there are sex differences in the interactions between the maternal THs trajectories and neonatal cognitive behavioral disorders.
Frontiers in Neuroscience, 2021
ObjectiveThyroid dysfunction (overt and subclinical) has been consistently linked to pregnancy adversity and abnormal fetal growth and development. Mood disorders such as anxiety, depression, and obsessive-compulsive disorder (OCD) are frequently diagnosed during pregnancy and at postpartum, and emerging evidence suggests association with impaired offspring neurodevelopment and growth. This study aimed to examine potential associations between thyroid function and mood symptoms during pregnancy and postpartum.DesignThis is a prospective study measuring thyroid hormones and assessing mood symptoms by employing specific questionnaires in the same cohort of 93 healthy pregnant women at the 24th (2nd trimester) and 36th (3rd trimester) gestational weeks and at the 1st postpartum week.MethodsSerum thyroid hormones, TSH, anti-TPO, and anti-Tg antibodies were measured at the 24th (2nd trimester) and 36th (3rd trimester) gestational weeks and at the 1st postpartum week. Specific validated q...
Archives of Endocrinology and Metabolism
Clinical and subclinical hypothyroidism are the most common hormonal dysfunctions during pregnancy. Insufficient maternal thyroid hormones (THs) in the early stages of pregnancy can lead to severe impairments in the development of the central nervous system because THs are critical to central nervous system development. In the fetus and after birth, THs participate in neurogenic processes, cell differentiation, neuronal activation, axonal growth, dendritic arborization, synaptogenesis and myelination. Although treatment is simple and effective, approximately 30% of pregnant women in Brazil with access to prenatal care have their first consultation after the first trimester of pregnancy, and any delay in diagnosis and resulting treatment delay may lead to cognitive impairment in children. This review summarizes the effects of clinical and subclinical hypothyroidism on fetal neurodevelopment, behavior and cognition in humans and rodents.