Effects of Early Thyroid Hormone Deficiency on Autobiographical Memory and Hippocampal Structure and Function during Late Childhood and Early Adolescence

The hippocampus, which is a critical brain region for episodic autobiographical memory (AM), is particularly vulnerable to damage following periods of early thyroid hormone (TH) deficiency. Although numerous studies have examined AM performance in adult patients with hippocampal damage, no study has yet examined AM in children exposed to early TH deficiency, such as children with congenital hypothyroidism (CH) and offspring of women who were hypothyroid during pregnancy (HYPO). Given that both animal and human studies have shown that early TH deficiency results in significant hippocampal abnormalities and memory impairments, the purpose of this dissertation was to investigate the effects of early TH deficiency on AM and hippocampal structure and function during childhood. 
\nStudy I examined AM performance in a large sample of typically developing children and adolescents in order to validate the use of the newly-developed Children’s Autobiographical Interview (CAI). In Study II, the CAI was used to investigate AM performance in children with early TH deficiency (i.e., CH and HYPO groups). Similar to the findings observed in adults with hippocampal damage, CH and HYPO groups both exhibited weaknesses in episodic AM, but not semantic AM, relative to controls. In addition, structural MRI revealed mild bilateral hippocampal volume reductions in HYPO, but not CH, which is consistent with animal models suggesting that early prenatal TH deficiency (i.e., HYPO) may be associated with greater abnormalities in hippocampal structure than postnatal TH deficiency (i.e., CH). Study III investigated children’s AM accuracy performance using a staged event and indicated that children with early TH deficiency had proportionally less accurate recollections of the staged event than controls. Importantly, smaller hippocampal volumes in both CH and HYPO groups predicted lower AM accuracy scores. Finally, in Study IV, functional MRI revealed that children with early TH deficiency exhibited abnormal (i.e., greater bilateral) hippocampal activation during episodic AM retrieval, but not during semantic AM retrieval, relative to controls, which may reflect neural compensation or may be a by-product of the degree of hippocampal damage. Overall, this dissertation provides critical new insight into the long-term effects of early TH deficiency on children’s AM performance and the hippocampus.

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