Abstract
The studies described in this thesis focus on the neuropsychological consequences in patients who have suffered Cushing¿s syndrome (CS, due to glucocorticoid excess) and acromegaly (due to excess of growth hormone -GH-). It is known that prolonged exposure to glucocorticoids may have long-lasting adverse effects in CS patients who do not completely return to premorbid level of functioning and quality of life despite long-term cure. Previous studies have showed smaller hippocampal volumes, enlarged ventricles, cerebral atrophy as well as alterations in neurochemical concentrations and functional brain activity in CS patients. On the other hand, in acromegalic patients, potential long-lasting effects of GH on the brain affecting personality, cognition and behaviour have not been considered until recently. Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Nevertheless, the presence of affective disorders in these patients is common.Making a choice is a common behavior in daily life and requires selecting one option among several alternative possibilities. The Iowa Gambling Task (IGT) is a measurement of decision making that mimics real-life risk taking situations since it involves uncertainty, reward and punishment. Frontal cortex has a key role in the IGT because it has the ability to coordinate processing among its millions of neurons in order to direct them towards future goals and advantageous decisions. The aims of these studies were to evaluate memory and decision making in patients with CS and acromegaly, and explore their relationship with frontal cortex and affective disorders.
Thirty-five CS patients and thirty-five matched controls were evaluated using the IGT and 3Tesla magnetic resonance imaging (MRI) to assess frontal cortical thickness. Thirty-one patients with acromegaly and thirty-one healthy controls were evaluated using the IGT, Rey Auditory Verbal Learning Test (RAVLT), State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory-II (BDI-II).
In the first study, CS patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards and higher number of riskier cards. They showed more difficulties than controls to learn the correct profiles of wins and losses for each card group. In whole brain analysis, CS patients showed decreased cortical thickness in the left superior frontal cortex, left precentral cortex, left insular cortex, left and right rostral anterior cingulate cortex, and right caudal middle frontal cortex compared to controls. In the second study, acromegalic patients showed impairments in delayed verbal memory and more anxiety and depressive symptoms than controls. Regarding the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards and higher number of the riskier cards. Multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found.
These studies show impaired decision making in both CS and acromegalic patients. They selected more disadvantageous choices than advantageous choices. Whereas healthy controls gradually learned to favor the advantageous decks, patients with acromegaly and CS continued to experience large punishment throughout training. We have not found a direct relationship between poor decision making and frontal cortical thinning in CS patients, opposite to previous studies on other clinical conditions. Decision deficits on the IGT were correlated with memory deficits in CS and acromegalic patients. Moreover, acromegalic patients show affective alterations (anxiety and depressive symptoms) that influenced delayed memory and decision making.
| Date of Award | 28 Jun 2016 |
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| Original language | Catalan |
| Supervisor | Elena Valassi (Director), Eugenia Resmini (Director) & Susan Webb Youdale (Director) |