Role of thyroid function in the intergenerational transmission of maternal childhood maltreatment effects

儿童期虐待的经历可能会在生物学上嵌入受虐待者的体内，并可能增加其在以后生活中对身心健康产生不良影响的风险。越来越多的证据表明，CM的这些不良后遗症可能会传递给下一代;然而，这种代际传递的时间窗口和机制尚未得到澄清。在拟议的项目中，我打算解决的假设，传播的不良后果CM已经开始在宫内发育期间通过改变妊娠甲状腺生物学。母体甲状腺激素的充足供应对胎儿大脑的正常发育和以后的认知功能至关重要。认知缺陷，反过来，往往先于相同的情绪和行为障碍，已观察到在儿童的CM母亲，因此可能代表一个敏感的标志物的疾病风险。因此，母体甲状腺功能可能在CM效应的代际传递中发挥机械作用。作为解决这一假设的第一步，目前的项目旨在阐明CM和甲状腺功能之间的关联在怀孕期间，以及认知发育的后代在生命的头两年在一个前瞻性的纵向研究。目前的建议的一个独特的优势是，目前正在招募一个非常好的特点的队列的240个母子二人组与CM和没有。在怀孕期间的三个时间点，心理社会压力及其生物学相关因素进行了评估。出生后（1，6，12，和24个月）进行婴儿发育和环境调节剂的系列措施（包括大脑的多模态成像）。目前的提案要求提供资金，以增加a）怀孕期间对母亲甲状腺功能（TSH、fT 4、fT 3、TT 4、rT 3、TPO-Ab、hCG）的测量，以及B）对12个月和24个月大的婴儿认知功能的详细测试。这项研究将揭示早期生活压力代际传递的原因和机制，并为早期干预策略提供信息。

Experience of childhood maltreatment (CM) may become biologically embedded in the exposed individual and may increase the risk for adverse mental and physical health effects later in life. Increasing evidence suggests that these adverse sequelae of CM may get transmitted to the next generation; however, the time window(s) and mechanisms of such intergenerational transmission have yet to be clarified. In the proposed project, I intend to address the hypothesis that transmission of the adverse consequences of CM commences already during the intrauterine period of development via alterations in gestational thyroid biology. An adequate supply with maternal thyroid hormones is of prime importance for normal fetal brain development and for cognitive functioning later in life. Cognitive deficits, in turn, often precede the same emotional and behavioral disorders that have been observed in children of CM-mothers und could thus represent a sensitive marker for disease risk. Maternal thyroid function could therefore have a mechanistic role in the intergenerational transmission of CM effects. As a first step addressing this hypothesis, the current project seeks to elucidate the associations between CM and thyroid function during pregnancy as well as cognitive development in the offspring in the first two years of life in a prospective longitudinal study. A unique strength of the current proposal is the availability of a very well-characterized cohort of 240 mother-child-dyads with and without CM that is currently being recruited. At three time points during pregnancy, psychosocial stress and its biological correlates are assessed. After birth (1, 6, 12, and 24 months) serial measures of infant development and environmental moderators are conducted (including multimodal imaging of the brain). The current proposal requests funds to add a) measures during pregnancy of maternal thyroid function (TSH, fT4, fT3, TT4, rT3, TPO-Ab, hCG), and b) detailed tests of infant cognitive function at 12 and 24 months of age. This study will shed light on the causes and mechanisms of intergenerational transmission of early life stress and inform early intervention strategies.