The 'totality' of psychosis: systematic comparison of the major psychotic diagnoses in the Cavan-Monaghan First Episode Psychosis Study (CAMFEPS)

Major psychotic disorders such as schizophrenia (SZ), bipolar disorder (BD) and major depressive disorder with psychotic features (MDDP) are global leading causes of disability-adjusted life years. Considerable advances in research into these disorders over the last few decades have resulted in more reliable operational diagnoses, improved treatment approaches and better outcomes. However, absence of neurobiological markers and high rates of cormorbidity mean that differentiating various psychotic disorders within the totality of psychosis and identifying boundaries between psychosis and normality remain unclear. While recent research on psychotic illness has focussed on the nosological, clinical and biological relationship between SZ and BD, little attention has been directed to the most common alternative psychotic diagnosis, major depressive disorder with psychotic features (MDDP). This thesis is based on a crossectional study within the Cavan-Monagahan First Episode Psychosis Study (CAMFEPS), a naturalistic study of patients characterised by substantive ethnic and socioeconomic homogeneity and stability. Its purpose is to systematically compare epidemiological, clinical and pathobiological characteristics of major DSM-IV psychotic diagnoses, including the BD specifier ‘with’ vs ‘without’ psychotic features, to better understand if these disorders are distinct entities or nodes on a continuum of psychotic illness. SZ, BD and MDDP emerged as the three major diagnostic groupings. The results indicated that each of these post hoc diagnoses share similar incident rates and can occur at any time over the adult lifespan in both males and females. While SZ and BD were primarily disorders of young adulthood, the first psychotic episode of MDDP was uniformly distributed across the adult lifespan; while the incidence of SZ was more common in males than in females, incidence o f BD and MDDP did not differ between the sexes. Relative to SZ, MDDP was characterised by similar negative symptoms, executive dysfunction, neurological soft signs, premorbid intellectual and social dysfunction, and quality of life; in contrast, BD was characterised by less prominent negative symptoms, executive dysfunction and neurological soft signs, and by better quality of life. These novel findings suggest that what we currently categorise as MDDP may be more closely aligned with SZ and BD than has been considered previously. They indicate that the intricacies of how psychosis is manifested vis-à-vis depression and mania may be occurring within a dimensional space, rather than validating categorical distinctions.