Executive Functioning in recurrent - and first episode Major Depressive Disorder: Longitudinal studies

Abstract

Major Depressive Disorder (MDD) is in the acute phase of illness often associated with neuropsychological impairment in a range of cognitive domains such as attention, memory, psychomotor speed and Executive Functioning (EF). However, the literature is inconclusive regarding the pattern of cognitive impairment in MDD and if these functions are state or trait dependent. MDD is one of the most common psychiatric disorders and is characterized by a high relapse risk. However, the factors affecting the vulnerability for relapse are still not well understood. his thesis is based on three papers that investigated EF in MDD, both in the acute phase of illness and in phases of symptom reduction and remission. The first paper investigated EF in a group of patients with recurrent unipolar MDD. The second and third paper investigated EF in a group of first- episode unipolar MDD patients. In all three papers, EF was investigated using neuropsychological tests from the Delis-Kaplan Executive Function System (D-KEFS). Paper I investigated EF in a group of recurrent unipolar MDD patients in a follow- up study. More specifically, the paper addressed the question if the impairment in the specific EF functions of inhibition and semantic fluency seen in the acute phase of illness would persist or be normalized with symptom reduction in a 9 month follow -up study. The results showed that the patient group was still impaired in inhibition, inhibition/switching and semantic fluency compared to the control group, despite significant symptom reduction. Performance in mental flexibility in general and phonemic fluency was equal to the control subjects. There were no association between depressive symptoms and EF impairment. The results further showed that the same patients that were impaired in inhibition in the acute phase of illness were still impaired at the follow- up assessment. Thus, seen in a 9 month perspective, the results indicate that inhibition may represent a stable trait characterizing patients with recurrent MDD. Paper II investigated EF in a group of first episode unipolar MDD patients in the acute phase of illness. More specifically, the paper addressed the question if the EF impairment that was found in the recurrent patient group also was evident in a group of first episode MDD patients. Inhibition, mental flexibility, phonemic- and semantic fluency, planning- and problem solving were investigated. The results showed that the patient group was impaired in the EF functions of inhibition, inhibition/switching and semantic fluency compared to the control group. The patient group did not show impairment in the other EF measures that were assessed, such as mental flexibility in general, phonemic fluency, planning and problem-solving. Furthermore, the patient group was impaired compared to the control group in three measures of processing speed. However, the results indicated that poor processing speed could not account for the poor EF performance. There was further no association between severity of depression and EF impairment. The results from paper II show that inhibition and semantic fluency are impaired in first episode MDD. Paper III investigated EF in a group of first episode unipolar MDD patients in a follow-up study. More specifically, the paper addressed the question if the impairment in inhibition and semantic fluency seen in the acute phase persisted or normalized in a longitudinal perspective of one year. In addition the third paper investigated if there was a relationship between poor inhibition and semantic fluency and the experience of relapse during the follow-up period. The EF of inhibition, mental flexibility, phonemic and semantic fluency was reinvestigated. Mean scores showed that the patients were in remission at the follow-up assessment. The results showed that the patient group still performed poorer in inhibition, inhibition/switching, semantic fluency and some measures of processing speed compared to the control group. Poor processing speed could however not solely account for the impaired performance in EF. In addition, the results showed that the performance in inhibition were more impaired when an additional requirement of mental flexibility was demanded. The performance in inhibition/switching at inclusion was further found to be more impaired in patients that experienced a relapse during the follow- up period, and found to enhance the likelihood of experiencing relapse. However, due to smallsample size and other possible confounding variables that could affecting the association found between tendency to relapse and poor performance in inhibition/switching in paper III, these results should be viewed as preliminary and thus be interpreted with caution. Taken together, the present thesis demonstrates that inhibition and semantic fluency are impaired in patients with MDD across the course of the disorder, and thus may represent stable, enduring cognitive traits in MDD independent of symptom severity. Further, the present thesis indicates that impaired inhibition with the additional requirement of mental flexibility may represent a vulnerability factor for the experience of relapse.