Utilize este identificador para referenciar este registo: http://hdl.handle.net/10451/27184
Título: Effects of dehydroepiandrosterone on cognition : an electrophysiological approach
Autor: Fernandes, Sónia Isabel do Vale, 1973-
Orientador: Martins, João Martin, 1957-
Micó, Carles Enric Escera
Palavras-chave: Desidroepiandrosterona (DHEA)
Personalidade
Memória
Atenção
Processamento emocional
Teses de doutoramento - 2016
Data de Defesa: 2016
Resumo: Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) physiologic role remain controversial. Central nervous system and behavioral effects have been described. DHEA and DHEAS have been hypothesised to play a role in cortical organization and brain maturation and suggested to have memory, attention and mood enhancement effects in humans. A neuro-stimulatory action and an anti-cortisol mechanism of action may contribute to those effects. Moreover, the balance between DHEA and DHEAS may modulate their effects in the central nervous system. The objective of this thesis was to explore behavioral correlates of DHEA and DHEAS in humans, in particular regarding personality, stress response, working memory and emotion. Relations at the performance and brain processing levels were explored. DHEA response to the performance of cognitive tasks was also analyzed. In study I we explored the relation between DHEAS and both pituitary-adrenal axis reactivity and personality in human subjects of both genders. This was a retrospective study of 120 patients assisted at the endocrine outpatient department of a public central Portuguese hospital, before medical treatment. Personality was evaluated with the Minnesota Multiphasic Personality Inventory (MMPI) and the pituitary-adrenal axis reactivity was assessed with the corticotrophin releasing hormone (CRH) test. Baseline serum DHEAS was inversely related to peak/baseline cortisol response to CRH infusion. DHEAS reactivity in the CRH test was directly related to the Deviant Behavior triad and type A personality. These results suggest higher DHEAS levels may be a protective factor against an excessive cortisol response under stressful situations and personality may be related to DHEAS reactivity. In studies II and III DHEA, DHEAS and cortisol relations to working memory and distraction were studied by recording the electroencephalogram of 23 young women performing a discriminatory (no working memory load) or 1-back (working memory load) task in an audio-visual oddball paradigm. We measured salivary DHEA, DHEAS and cortisol both before each task and at 30 and 60 min intervals. In study II, we showed that under working memory load, a higher baseline cortisol/DHEA ratio was related to higher distraction as indexed by an enhanced novelty-P3. This suggests that cortisol may lead to increased distraction whereas DHEA may hinder distraction by leading to lower processing of the distractor. An increased DHEA production with consecutive cognitive tasks was found, and higher DHEA responses attributed to working memory load were related to enhanced working memory processing as indexed by an enhanced visual P300. Overall, the results suggest that in women DHEA may oppose cortisol effects, reducing distraction and that a higher DHEA response may enhance working memory at the electrophysiological level. In study III we used that same group of subjects and protocol to analyze the DHEAS/DHEA ratio relation to involuntary attention during the performance of a working memory task. Higher DHEAS/DHEA ratio was related to enhanced auditory novelty-P3 amplitudes during the performance of the working memory task, but there was no significant relation to visual P300 amplitudes, novelty-P3 latencies or visual P300 latencies. Therefore, a relation between higher DHEAS/DHEA ratio and enhanced involuntary attention to the surrounding world without a deleterious effect on working memory processing is suggested. These results also suggest that the balance between DHEAS and DHEA may modulate attentional resources and the importance of the sulfotransferase and sulfatase activity in the modulation of DHEA and DHEAS central nervous system effects. In study IV we explored DHEAS, DHEA and cortisol relations to the processing of negative emotional stimuli at behavioral and brain levels by recording the electroencephalogram of 21 young women while performing a visual task with implicit neutral or negative emotional content in an audio-visual oddball paradigm. For each condition, salivary DHEA, DHEAS and cortisol were measured before performing the task, and at 30 and 60 min intervals. DHEA increased after task performance, independently of the implicit emotional content. With implicit negative emotion, higher DHEAS/DHEA and DHEA/cortisol ratios before task performance were related to shorter visual P300 latencies suggesting faster brain processing under a negative emotional context. In addition, higher DHEAS/DHEA ratios were related to reduced visual P300 amplitudes, indicating less processing of the negative emotional stimuli. With this study, we could show that at the electrophysiological level, higher DHEAS/DHEA and DHEA/cortisol ratios were related to shorter stimulus evaluation times, suggesting less interference of the implicit negative content of the stimuli with the task. Furthermore, higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually constitute a protective mechanism against negative information overload. In conclusion, these studies showed several behavioral correlates of DHEA and DHEAS. Additionally, the results suggest anti-cortisol effects of DHEA and DHEAS and the importance of the balance between DHEAS and DHEA. DHEA levels increased after the performance of cognitive tasks, more so after a working memory load than a no working memory load task, suggesting that cognitive tasks may modulate DHEA levels. Higher baseline DHEAS levels were related to reduced cortisol response to CRH suggesting a protective effect during the stress response. In addition, significant new findings were described regarding DHEA and DHEAS relations to working memory, emotion and attention at the brain processing level. Those results suggest DHEA may eventually oppose cortisol effects reducing distraction while higher DHEAS/DHEA ratios may enhance involuntary attention to the surrounding world during the performance of working memory tasks with no evident deleterious effects on the working memory load task in course. On the other hand, higher DHEA response may enhance working memory at the electrophysiological level. Regarding emotional processing, higher DHEAS/DHEA and DHEA/cortisol ratios may be related to less interference of the implicit negative content of the stimuli and higher DHEAS/DHEA ratios were related to reduced processing of negative emotional stimuli which may eventually protect against negative information overload. In short, results suggest DHEAS levels may be related to personality and reduced cortisol stress response while studies at brain processing level suggest DHEA and/or DHEAS may enhance working memory / attention and reduce the processing of negative information.
Descrição: Tese de doutoramento, Medicina (Endocrinologia), Universidade de Lisboa, Faculdade de Medicina, 2016
URI: http://hdl.handle.net/10451/27184
Designação: Doutoramento em Medicina
Aparece nas colecções:FM - Teses de Doutoramento

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