The Schizophrenia Prodrome Revisited: A Neurodevelopmental Perspective

Abstract

Despite the widespread acceptance of the neurodevelopmental model of schizophrenia, its application to research concerned with the prodromal phase of illness is limited. Little recognition has been given to the concept of an enduring biological vulnerability to illness that may be responsive to early intervention. Rather, the focus of most prodromal studies is on emerging positive symptoms. The Recognition and Prevention (RAP) program follows the strategy of being equally concerned with the nonspecific symptoms reflecting the core of schizophrenia and those directly related to psychosis. Data were collected from 62 adolescents (mean age = 16.4 years) during the initial 3-year pilot phase of the RAP program (1998-2001). Subjects were divided into three clinical high-risk groups, characterized by (1) negative and nonspecific symptoms (e.g., social isolation, school failures), the earliest prodrome stage; (2) emerging attenuated positive symptoms of moderate intensity; and (3) severe attenuated (but subpsychotic) positive symptoms, considered most proximal to psychosis. Four risk factors, derived from the neurodevelopmental literature, were selected to reflect the vulnerability core: cognitive deficits, affective disturbances, social isolation, and school failure. All four domains were equally impaired across the three risk groups, supporting the presence of the underlying vulnerability core regardless of the magnitude of emerging positive symptoms. An observational pilot study was also conducted to identify the medications typically used to treat emerging positive symptoms. Antidepressants were used as frequently as antipsychotics to treat adolescents presenting with moderate attenuated positive symptoms. Regardless of type of medication, moderately symptomatic youngsters did quite well over the approximately 1-year followup period. By contrast, adolescents presenting with more severe (but nonpsychotic) attenuated symptoms were treated with antipsychotics, often in combination with other agents. Outcome for the more symptomatic youngsters was, however, more guarded, with nearly half (i.e., 47%) of the group converting to a schizophrenia spectrum psychotic disorder. Nonadherence to medication appeared to be a major risk factor in this group. We conclude that a neurodevelopmental model of schizophrenia is supported by our data and that a range of novel treatment strategies may be neuroprotective by directly affecting the disorder's vulnerability core.

A Severity-Based Clinical Staging Model for the Psychosis Prodrome: Longitudinal Findings From the New York Recognition and Prevention Program

“…Cornblatt and colleagues [19][20][21] at the Recognition and Prevention (RAP) Program of the Zucker Hillside Hospital in New York proposed a somewhat different classification system in the late 1990s that was grounded in the theoretical work by Mrazek and Haggerty 22 and the neurodevelopment approach proposed by Weinberger.…”

“…Therefore, critical to this model is the notion that there are 2 independent processes involved in developing a full-blown psychotic illness. The presence of either one alone can lead to poor long-term prognosis, 21,25 but the interaction between these 2 pathways is thought to lead to emergence of full-blown psychosis.…”

The Role of Cognition and Social Functioning as Predictors in the Transition to Psychosis for Youth With Attenuated Psychotic Symptoms

“…12 In their recent study at the Recognition and Prevention (RAP) Program they excluded those who met BIPS and GRD criteria and selected their potential predictor variables primarily based on the vulnerability indicators they had described many years earlier. 13 These included cognitive deficits, anxiety and depression, and social and role functioning difficulties. These domains had been selected as they were the domains most implicated in schizophrenia and were potentially modifiable.…”

Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome

“…We therefore argue that the study of negative symptoms is critical as they have a higher prevalence than positive symptoms in the prodromal psychotic phase (Cornblatt et al, 2003;McGlashan et al, 2001;Phillips et al, 2005;Schultze-Lutter et al, 2010). Negative symptoms are often accompanied by cognitive deficits (Addington et al, 1991;Basso et al, 1998), worse psychosis outcome (Milev et al, 2005), social impairments (Lincoln et al, 2011;Milev et al, 2005), and poorer occupational and daily functioning (Milev et al, 2005;Rabinowitz et al, 2012).…”