Prospective Study of Psychobiology in First-episode Schizophrenia at Hillside Hospital

Abstract

Heterogeneity has been a consistent problem in the research and treatment of schizophrenia. Despite marked variation in the onset, phenomenology, treatment response and outcome of schizophrenic patients, our ability to identify subtypes is remarkably limited. A major problem in schizophrenia research has been the use of cross-sectional study designs and heterogeneous patient samples at different stages of the illness and who have been previously exposed to neuroleptics which have potentially confounding effects on the disease. This study intends to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospective, longitudinal, repeated measures design assessing biologic and clinical parameters including measures of psychopathology, side effects, and social adjustment to examine clinical variables of treatment response, illness course, and outcome; measures of central nervous system dopamine activity and brain morphology in patients, from the onset of their illness. Patients were ascertained at hospital admission and assessed with a battery of clinical, neuropsychologic, and biologic measures before undergoing standardized treatment for the acute and maintenance phases of the illness. Upon completion, approximately 120 first-episode patients will have entered the study and will have been followed prospectively for up to 5 years and assessed at specific time intervals. Preliminary results reveal significant abnormalities in brain morphology, growth hormone secretion, eye movement function, and psychotogenic response to dopamine agonists in first-episode, treatment-naive patients which are associated with treatment response and outcome. This article describes the study's rationale, design, and methods, and a summary of the published results to date. These are discussed in terms of their significance for putative clinical subtypes and pathophysiological models of schizophrenia.

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

“…There is also no reason to suspect that the sample is not representative of the schizophrenia patient population since similar prevalence rates of intellectual preservation reported by other investigators were observed in this study. Further, total patient mean IQ of approximately 89 in this study is consistent with others, and the sex ratios are also similar to those reported by others Lieberman et al, 1992;Mortensen et al, 1999).…”

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

“…Introduction fifth and one-third, will derive little benefit from conventional antipsychotic drug therapy, although a smaller proportion would seem to be completely resistant, [36][37][38] Studies of first episode schizophrenia suggest that, even at an early stage of the illness, a small proportion of patients will show a lack of response, commonly leading to a protracted hospital admission. 38,39 Historically, the concept of non-response to antipsychotic medication was ill defined and largely synonymous with persistent or frequent hospitalisation.…”

“…38,39 Historically, the concept of non-response to antipsychotic medication was ill defined and largely synonymous with persistent or frequent hospitalisation. 37 The use of a criterion threshold reduction in the score on a standardised psychopathology rating scale (such as 20% or 50% reduction on the BPRS total score) has allowed for more reproducible and consistent definitions of poor response to antipsychotic medication.…”

Treatment–Refractory Schizophrenia

“…However, this attempt has been fraught with both scientific and conceptual difficulties. Epidemiological data have revealed that male gender, 8,39,40 early age of onset of illness, [41][42][43] positive family history of schizophrenia, 44,45 obstetric complications, 46 absence of affective symptoms, 47 severe and lengthy premorbid manifestations, 39,45,48,49 longer duration of untreated psychosis, 50,51 severe negative and cognitive symptoms, 52,53 presence of soft neurological signs, early onset of abnormal involuntary movements, 54 and low level of social functioning 55 were all associated with some degree of treatment refractoriness. However, the reported associations have generally been weak and inconsistent.…”