Neurological soft signs in the prodrome of schizophrenia

This thesis titled “Neurological soft signs in the prodrome of schizophrenia” was submitted by Dr Kishen Neelam to The University of Manchester for theprodrome of schizophrenia. The currently recognised approaches to identify the prodrome of schizophrenia involve complex psychopathological interviews. Although, these have shown promising results they are not at a level one would like to achieve in clinical practice. There is still a need to improve the clinical validity of the prodrome assessments. Neurological soft signs (NSS) are subtle but observable impairments in motor and sensory functions that are believed to be common in schizophrenia. The elicitation of NSS has the potential to improve accurate detection of the prodrome of schizophrenia.The thesis has two broad aims, a) to examine rates of NSS and establish how far NSS behave as an endophenotype for schizophrenia by undertaking meta-analyses, and b) to explore the potential of NSS as an adjunct prodrome assessment tool using a service evaluation approach. The thesis presents three interconnected studies: 1) a systematic review and meta-analysis of NSS in schizophrenia, 2) a systematic review and meta-analysis examining familial association of NSS, and 3) a service evaluation of a prodrome clinic that examined for NSS and conversion to psychosis. The meta-analyses involved systematic search in EMBASE, MEDLINE and PsycINFO identifying studies examining NSS in schizophrenia. The prodrome clinic examined for NSS, Schizotypy (SPQ-A), Attenuated Psychosis (CAARMS), Basic symptoms (SPI-A) and functioning in young adults from Lancashire Early Intervention Services.Chapter 5 describes the first systematic review and meta-analysis that demonstrates the meaning of NSS in schizophrenia. Chapter 6 describes the second systematic review and meta-analysis that rigorously examines NSS for the endophenotype criterion of familial association. Chapter 7 reports on the correlates of NSS in early psychosis and prodromal patients. It highlights the relationship of NSS with demographic and clinical measures including schizotypy, attenuated psychosis, basic symptoms and functioning. Chapter 8 describes the role of NSS in an NHS prodrome clinic. It explores the potential of NSS to improve the detection of people likely to develop psychosis. The service evaluation overall examined the initial idea of the potential use of NSS as a clinical tool to augment the predictive ability of psychopathological approaches. The thesis identified the effectiveness of NSS in the prodrome assessment process. Examining neurological soft signs is inexpensive, reliable and easy to learn and apply in clinical settings. The thesis suggests neurological soft signs to be an independent risk factor possibly related to an underlying diathesis and disease process for schizophrenia. Prospective diagnostic studies with large sample size and standardized interview based follow-up are required to establish how far the identification of soft signs can improve the prediction of actual psychosis. The thesis emphasizes the important clinical and research implications of neurological soft signs in the early detection of schizophrenia.