From early life stress to depression: assessment of HPA axis activity and cognitive function

Abstract

The interest in understanding the mechanisms responsible for the association between stress and cognitive symptoms of depression has increased significantly. Chronic exposure to stress, and consequently elevated levels of corticosteroids, results in changes in cognitive processes similar to those observed in depression. Evidence suggests that adverse experiences early in life combined with the genetic background result in the sensitization of certain brain circuits to a stressor, even influencing the reactivity of the HPA axis. Exposure to stress in neural development phase would be associated with reduction in hippocampal volume. Also, several findings suggest that changes resulting from mistreatment or abuse in childhood would increase the risk for depression. In this field, individual differences in brain interpretations of the environmental challenges and the reactions of the organism are important determinants of the response of vulnerability or resilience to the consequences of stress. Furthermore, studies show that psychological processes may determine the magnitude of the stress response. Thus, the ability to predict the following events and exercise control over the situation can be considered an important modulator of stress response and its consequences. Within this perspective, researchers argue that the role of cognitive factors in depression needs to be better studied. Moreover, is important to clarify the influence of early life stress on HPA axis activity and in the etiology of depressive symptoms, including cognitive impairment. Therefore, this study aims to investigate the HPA axis activity and function of the hippocampus and prefrontal cortex in cognition of people with a history of depression associated with early life stress. The research will be conducted in the psychiatric service of the Hospital of the Faculty of Medicine of Ribeirao Preto, University of Sao Paulo. 100 participants will be selected, 60 of them showing current diagnosis of depression and 40 healthy subjects. Patients will be further divided between those with a history of early life stress and those without. All participants will be assessed for the history and current psychiatric status, and cognitive functions. Participants in the clinical group will have the diagnosis confirmed by Mini International Neuropsychiatric Interview (MINI). They will also be assessed for personality traits by the Temperament and Character Inventory; symptom severity using the Hamilton Scale for Depression (HAMD), Beck Depression Inventory (BDI-II), Beck Hopelessness Scale (BHS) and Beck Anxiety Inventory (BAI), risk of suicidality with Beck scale for Suicidal Ideation (BSI), and early life stress with the Childhood Trauma Questionnaire (CTQ). All participants will also undergo a psychological assessment battery to evaluate cognitive functions. This procedure will be carried out using the Wechsler Intelligence Scale for Adults (WAIS III), Test Wisconsin Card Sorting Test (WCST) and Complex Figure Test of Rey. Neuroendocrinologic evaluation will be performed by collecting six samples of salivary cortisol in a 24-hour period. Statistical analysis will be performed with parametric or non-parametric tests when appropriate. (AU)