Olfaction in First Episode Psychosis Study, Melbourne Neuropsychiatry Centre

This project involved collection of neuropsychological data from first episode psychosis patients at the Aubrey Lewis unit at Royal Park Hospital.
A challenge inherent to understanding schizophrenia is to distinguish between primary and secondary disease processes and their associated symptomatology. Neuropsychological approaches to this challenge are examined in this thesis along with an overview of attempts to identify syndromal patterns. Relationships between these syndromes and their influence on cognitive function are also described, particularly with reference to possible underlying biological compromise. This description forms a rationale for the aims of the thesis that include an examination of cognition as possible marker of functional compromise of circuitry implicated in schizophrenia. Olfactory processing over the course from high risk to chronic schizophrenia is described. Identification of olfactory deficits early in the course of psychosis are found to implicate relatively specific prefrontal circuits that are associated with both syndromal and cognitive patterns of behaviour, after the confounds of acuity, substance abuse, medication and general cognitive ability are taken into account. Patterns of olfactory ability across the spectrum of psychosis are then compared to those found to be characteristic of a temporal lobe epilepsy group with the aim of comparing and contrasting the functional integrity of implicated circuitry in psychosis. Results support the potential for olfactory tasks to be used as probes of function in related circuitry, and particularly for detecting early signs of impending psychotic discharge. While the degree of cognitive deficits may be exacerbated over the course of the illness in accordance with the neurodegenerative hypothesis, identification of patterns of compromised function that implicates the fronto-limbic axis before the first psychotic discharge are also consistent with the neurodevelopmental hypothesis of schizophrenia.

This project recruited over 100 participants.

Time period: 1994-1999

本研究收集了皇家公园医院（Royal Park Hospital）奥布里·刘易斯病区（Aubrey Lewis Unit）的首发精神病（first episode psychosis）患者的神经心理学数据。

理解精神分裂症的固有挑战之一，在于区分原发性与继发性疾病进程及其伴随的症状学表现。本论文探讨了应对该挑战的神经心理学研究路径，并综述了识别症状群模式的相关尝试。同时阐述了此类症状群之间的关联，及其对认知功能的影响，尤其聚焦于潜在的生物学受损机制。上述论述为本论文的研究目标奠定了理论基础：本研究旨在将认知功能作为精神分裂症相关神经环路功能受损的潜在标志物进行考察。

本研究还阐述了从精神分裂症高危人群到慢性患者的嗅觉加工过程。在控制了病情严重程度、物质滥用、药物治疗及总体认知能力等混淆变量后，本研究发现：精神病早期出现的嗅觉功能缺损，可关联到相对特异性的前额叶环路，该环路同时与行为的症状学模式及认知模式相关。

随后，本研究将精神病谱系群体的嗅觉能力模式，与颞叶癫痫群体的典型嗅觉能力模式进行对比，以考察并对比精神病相关神经环路的功能完整性。

研究结果证实，嗅觉任务可作为相关神经环路功能的检测探针，尤其适用于识别即将出现精神病性发作的早期迹象。尽管根据神经退行性假说，认知缺损的程度可能随病程进展而加重，但本研究在首次精神病性发作前即识别出累及额-边缘轴的功能受损模式，这一结果也与精神分裂症的神经发育假说相契合。

本研究共招募100余名参与者，研究周期为1994年至1999年。