Neuropsychological and brain functional changes across the different phases of schizoaffective disorder

Abstract

The term schizoaffective psychosis was introduced by Kasanin in 1933 to describe the apparent occurrence of patients who did not fit into the category of either schizophrenia or manic-depressive psychosis. Ever since, its nosology has been a matter of controversy and studies have been scarce dedicated to shed light into the neurobiology of this disorder. The present thesis aimed to add insight to the literature of neurobiological underpinnings of schizoaffective disorder, taking into account also longitudinal aspects of the disease. Specifically, the thesis reports two fMRI studies which examined a sample of patients meeting both RDC and DSM-IV criteria for schizoaffective disorder, bipolar type. This patient sample was compared with age, sex and premorbid-IQ matched healthy controls. All subjects underwent at least one fMRI scan, during performance of the n-back working memory test. Additionally, memory and executive functioning were assessed. Linear models were used to obtain maps of activations and de-activations in the groups. The first study was a cross-sectional study evaluating patterns of brain activation and de-activation in acute schizomanic or schizodepressive schizoaffective patients. Compared to controls, the schizoaffective patients showed a reduced activation in the DLPFC and also a failure of de-activation in the medial frontal cortex. This latter area corresponds to the anterior node of the DMN. In the second study the same patients were reassessed after at least two months of clinical remission. The subgroup of schizomanic patients were found to show a reversible frontal hypoactivation during n-back performance when compared to clinical remission, while no changes in the brain response to the task were seen in schizodepressive patients in comparison to clinical remission. The whole group of schizoaffective patients in clinical remission showed a failure of de-activation in the medial frontal cortex compared to the healthy controls. The cognitive assessment in the second study showed that schizomanic patients improved in memory but not in executive functioning from active illness to remission, while schizodepressive patients did not show changes in either domain. All schizoaffective patients in clinical remission continued to show memory and executive impairment compared to the controls. Overall, the present thesis suggests that DLPFC hypoactivation is a state feature of schizoaffective disorder. This finding aligns it with schizophrenia but also with bipolar disorder, where reduced DLPFC activity has also been described. Failure of de-activation, and by extension DMN dysfunction, appeared across all different phases of the disorder, as a trait feature of the illness. DMN dysfunction has also been described in a range of psychiatric disorders, including schizophrenia and bipolar disorder. Cognitive impairment was a further finding of this thesis. There was some evidence of memory improvement in euthymic schizomanic patients, but this was partial and the patients still showed deficits in remission, in particular executive dysfunction.

Date of Award	8 Jun 2015
Original language	English
Supervisor	Benedikt Lorenz Amann (Director), Edith Pomarol-Clotet (Director) & Adolfo Tobeña Pallares (Director)