City Research Online

Abstract

Schizophrenia is a complex psychiatric disorder with positive, negative, and cognitive symptoms. The causes are not yet fully understood, but it is believed that together with a strong genetic foundation, a ‘second environmental hit’ may be responsible to triggering a psychotic episode. Early-onset schizophrenia (EOS) a rare and more severe form of the disorder compared to its adult-onset counterpart and it is regarded to be more genetically loaded. This being as children and adolescents are less likely to have accumulated environmental triggers that are often considered risks to develop schizophrenia. Neurotic personality and anxiety symptoms are considered candidate schizophrenia risk factors. Working memory (WM) performance, the ability to hold information “online” in the matter of a few seconds, as well as its neural correlates are severely impaired in EOS, and such impairment is considered endophenotypic to the disorder. In addition, the expression of neurophysiological indices of cognition such as the mismatch negativity (MMN) and P300 event-related potentials (ERPs) are consistently demonstrated to be reliable biomarkers for the disorder, as shown by electroencephalography. This thesis on one hand, explores the influence of neuroticism and anxiety levels in healthy participants in ERPs during the auditory roving oddball and the hollow mask illusion experiments that are continually shown to be affected in schizophrenia literature. On the other hand, it explores meta-analytically convergent structural and functional brain abnormalities in EOS literature and follows a longitudinal fMRI cohort of EOS and healthy adolescents who were scanned twice in a 4-year span, while they performed the n-back task (WM task). These experiments are aimed to reveal brain areas that may qualify as endophenotypic markers of impaired WM neurodevelopment in schizophrenia. Our results showed that anxiety and neuroticism do not fully explain their status as schizophrenia risk factors by their relationship with the schizophrenia biomarker ERPs (P50 sensory gating, MMN, P300 and P600). The meta- analysis strongly indicates that a dysfunction in the functional network that underlies salience and other executive functions related to incentive and goal-oriented processes may be central across cognitive paradigms in EOS. Longitudinally, functional connectivity and maturation impairments are prevalent in the WM functional substrate of adolescents with EOS as they undergo neurodevelopmental processes by transitioning into early adulthood.

Publication Type:	Thesis (Doctoral)
Subjects:	B Philosophy. Psychology. Religion > BF Psychology
Departments:	Doctoral Theses School of Health & Psychological Sciences > Psychology School of Health & Psychological Sciences > School of Health & Psychological Sciences Doctoral Theses

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