The effects of estrogen treatment on neurocognition in healthy young women and women with schizophrenia

The wealth of biochemical, molecular and behavioural evidence to support estrogen, in particular ‘estradiol’ (E2), as a neuroprotective agent in the brain has lead to the proposal of estrogens as possible treatment for the cognitive deficits inherent to various neurological and mental disorders, such as schizophrenia. Despite this, the mechanisms underlying E2’s actions in the brain are largely unknown, although the cholinergic system shows promise as a key modulator of E2 effects, given the prominent role of this neurotransmitter system in fundamental cognitive processes. Therefore the aim of this thesis was to investigate the cognitive effects of one month of 100μg/day transdermal E2 treatment in healthy young women (Experiment One) and women of child-bearing age with schizophrenia (Experiment Two). In addition, the role of the cholinergic system in mediating the cognitive effects of estrogen was also explored in our sample of healthy young women. Both experiments were placebo-controlled randomized double-blind designs and examined the following cognitive domains: declarative verbal memory and learning, verbal fluency, working/visual memory, attention, cognitive flexibility and information processing/psychomotor speed. Short-term E2 treatment in healthy young women had selective positive effects on delayed verbal recall and spatial working memory, however the majority of cognitive domains were unaffected. Furthermore, overall E2 treatment did not protect against (or attenuate) the cognitive deficits induced by the muscarinic receptor antagonist scopolamine. In addition, one month E2 treatment did not improve cognitive functioning for our sample of women with schizophrenia. These findings add to the already largely inconsistent literature and highlight the complex effects of E2 treatment on cognitive function, which may be further influenced by age, endogenous estrogen levels and duration of treatment. These findings suggest that adjunctive E2 treatment may not be an effective treatment for cognitive deficits in women of child-bearing age with schizophrenia. However, given these are two of the few studies to have investigated the cognitive effects of E2 treatment in this age cohort, further research is required before definitive conclusions can be drawn. Future research should investigate the cognitive effects of E2 in post-menopausal women with schizophrenia and focus on alternative means for improving cognitive deficits. Further investigation into the underlying neurochemical mechanisms of estrogen in the human brain is also needed to help determine the nature of estrogen’s variable effects on cognitive function and it’s role in the pathophysiology of schizophrenia and related disorders.