Thesis (PhD)--Stellenbosch University, 2014. / ENGLISH ABSTRACT: Background The changes in cognition, brain structure, and neurological soft signs which are characteristic of schizophrenia appear to have been present before the onset of the phenotype. They therefore find relevance as potential vulnerability markers of the disease. Neurological soft signs are of particular interest because they can be elicited quickly, reliably and cheaply. They have also been touted as markers of certain characteristics of schizophrenia. The most convincing evidence for these assertions come from prospective longitudinal studies of first episode, medication naive patients with schizophrenia. Most of these studies have been based on wholly Caucasian or mixed samples of Caucasians and other races. The present study provides important reference data on the nature of neurological soft signs in indigenous African subjects and clarifies the trait or state marking signs in this population. Method A total of 84 patients with first episode, schizophrenia, schizo-affective disorder, or schizophreniform disorder meeting criteria in the fourth edition of the Diagnostic and Statistical Manual for Mental Disorders were consecutively recruited. Information on demographic characteristics, personal medical and psychiatric history, as well as family history was obtained at baseline. Neurological assessment was based on the 26 item Neurological Evaluation Scale. An exploratory factor analysis of the items in the scale was conducted using the baseline measurements. The derived sub-sets of neurological soft signs were then followed up longitudinally and in parallel with the ‘functional categories’ of the signs. The study describes the profile of neurological soft signs across the one year course of schizophrenia, as well as their relationship with a wide range of clinical and outcome variables. The severity of the baseline psychopathology was evaluated by administering the Positive and Negative Syndrome Scale. The overall clinical status was assessed using Clinical Global Impression. Additional assessments included the Calvary Depression Scale for Schizophrenia, Birchwood Insight Scale, Social and Occupational Functioning Assessment Scale, and the World Health Organisation Quality of Life Scale (WHO QoL-BREF). Pre-morbid adjustment was assessed using the Pre morbid Adjustment Scale, while extra-pyramidal effect of antipsychotics was assessed using the Extra-pyramidal Symptoms Rating Scale. Assessments were repeated at three monthly intervals for the full 12 months. Results Neurological soft signs were present in 96.4% of the sample at baseline. The signs loaded into a four factor structure: perceptual and motor sequencing (audio-visual integration, fist-edge palm, rhythm tapping, extinction, and right-left confusion), eye movements (synkinesis, convergence, and gaze impersistence), motor co-ordination and graphaesthesia (tandem walk, adventitious flow, and graphaesthesia), as well as stegreognosis. The scores for the perceptual and motor sequencing factor, as well as those for the sequencing of complex motor acts ‘functional category’ were stable across three measurements over 12 months (F=1.26, p=0.287, and F=1.87, p=0.158 respectively). The sequencing of complex motor act signs was not significantly correlated with the clinical and outcome characteristics of schizophrenia. However, other signs, as well as the NES total score were significantly correlated with more severe negative and disorganized psychopathology, as well as poorer outcome in terms of functioning and quality of life. Conclusion Neurological soft signs were present at a high frequency at baseline. A preponderance of the signs was associated with a more severe negative and disorganization psychopathology, as well as a poorer functional outcome and quality of life. Abnormal sequencing of complex motor act signs, and signs of abnormal cognitive processing of perceptual stimuli where resistant to changes in psychopathology, and thus may represent viable trait markers for schizophrenia in this cohort.