An investigation of neuroanatomical contributions to cognitive deficits associated with psychotic illness: A 4 year longitudinal follow-up study

Abstract

Introduction: In general, individuals who experience a first-episode of psychosis (FEP) display deficits on a wide range of neuropsychological tasks compared to psychiatrically healthy individuals (Bora et al., 2014). Performance is poorer on tasks such as visual learning, working memory, executive functioning, attention, social cognition and processing speed with verbal learning, in particular, being one of the most consistently reported cognitive deficits in schizophrenia (Mesholam-Gately et al., 2009; Aas et al, 2014). This study aimed to examine the trajectory of cognitive deficits after an initial psychotic episode and to identify neuroanatomical abnormalities that are associated with cognitive domains which exhibit the poorest course over time. Method: Using a cognitive battery specifically designed for researching cognitive impairments in schizophrenia, the MATRICS Consensus Cognitive Battery, this research investigated cognitive deficits at the presentation of a first psychotic episode and four years later. Cognitive profiles of age and gender matched healthy controls were also assessed at the same time points. All participants underwent structural MR scanning at the two time points. Cross-sectional neuroanatomical investigations were conducted with data from the four year time point, which also included a diffusion tensor imaging acquisition. These structural and diffusion MR analyses were conducted to assess whether the presence of neuroanatomical abnormalities was associated with the cognitive domains found to have the most progressive course following a first psychotic episode, namely verbal learning and processing speed. Specifically, (i) the arcuate fasciculus language-related network was investigated in relation to verbal cognition and (ii), due to the global operational nature of processing speed, a specifically chosen selection of global brain estimations were investigated in relation to processing speed deficits. Results: Individuals with psychosis performed significantly more poorly on all cognitive domains compared to psychiatrically healthy controls. Longitudinally, an initial psychotic episode appeared to be associated with an additional cost on verbal learning and two measures of processing speed over four years as these cognitive domains had marked poorer trajectory compared to the remaining cognitive domains (visual learning, working memory, attention and vigilance, reasoning and problem solving and social cognition). The neuroanatomical substrates for normal processing of verbal cognitive skills appeared to be altered in individuals with recent-onset psychosis, involving an aberrant role of right hemisphere fronto-temporal cortical regions. In relation to the processing speed composite score, divergent associations of global brain topology and interhemispheric integrity were found in controls and individuals with psychosis particularly with a visuo-spatial subscale, the symbol coding task, which may be indicative of pathology in the global interconnectedness of the brain in relation to processing speed impairments in psychosis. Abnormal associations in temporal lobe efficiency and anisotropy of the genu of the corpus callosum were associated with another visuo-spatial subscale of the processing speed composite score, the Trail Making Test. Conclusion: The findings of this thesis indicate that predominantly deficits of cognition remain stable four years following psychosis onset, with the exception of verbal learning and two measures of processing speed which presented with poorer longitudinal deficits in individuals with psychosis compared with controls. Investigations of the neural substrates of these cognitive domains revealed specific associations between neuroanatomy and cognition which contrasted between individuals with psychosis and controls and may be indicative of abnormalities in the neural substrates underlying verbal learning and processing speed performance in psychosis. In integrating the results of the neuroanatomical investigations, which employ different cognitive and neuroimaging methodologies, evidence emerged for a tentative shared abnormal neural substrate underpinning frontal and temporal regions. The neurodevelopmental model of schizophrenia identifies abnormal development in parietal regions in early adolescence followed by frontal and temporal cortices in later adolescence which coincide with the extent of first-episode psychosis and chronic cases in adulthood. As the course of verbal learning and processing speed follow a less stable trajectory four years following a first-episode, a continuation of these frontal-temporal disturbances may extend throughout illness course resulting in more chronic deficits in these two areas of cognition. Identifying specific anomalies in the brain which are associated with cognitive deficit progression in psychosis carries the potential to be targeted as biomarkers of the disorder, which could be especially beneficial in early disease detection as cognitive impairments primarily predate clinical symptoms.2019-02-2