This proposal seeks to characterize the early course of psychotic disorders and to
identify clinical and biological predictors of outcome. The large sample (=320) required
will necessitate a multi-site study. All B-SNIP sites have coordinated specialty services
for early course psychosis and have harmonized study procedures for uniform data
collection. Each site will recruit 1/5 of the participants; The project will be managed
by an all-site steering committee meeting weekly. Boston will be the coordinating site.
The outcome of early course psychosis (EP) is heterogeneous, ranging from early full
recovery to treatment resistance and functional decline from the onset of illness. The
ability to predict individual level outcomes would be highly valuable for treatment
planning and for tailoring the duration and intensity of psychosocial and pharmacological
interventions. Clinical features related to early psychosis onset are poor predictors of
remission and recovery. At the same time, the field has not yet established the clinical
utility of promising findings from decades of biomarker development/neuroscience
research, especially in EP patients for whom empirically guided treatment planning may
have the greatest impact. For example, neurocognitive, electroencephalographic (EEG) and
imaging biomarkers early in the illness may predict outcome, but used individually, their
prognostic value is limited. Multivariate approaches to clinical and neurobiological
features may offer better value for outcome prediction.
Toward this goal, we will leverage the biomarker (EEG, eye movement testing, and
neurocognition) based categorization of a cross-diagnostic sample of psychosis (biotypes)
developed, replicated and validated by our Bipolar-Schizophrenia Network for Intermediate
Phenotypes (B-SNIP) consortium. We have shown that Biotype-1, characterized by impaired
cognition and decreased sensorimotor responses to salient stimuli is associated with the
most severe impairments in functioning. Biotype-2 have the same level of cognitive
impairment as Biotype-1 but increased sensorimotor reactivity. Biotype-3 cases are
relatively normal on these measures and have the least impairments. These subgroups are
not synonymous with DSM diagnosis and are not captured by any individual variable. We do
not know if this categorization is predictive of symptomatic and functional outcome,
given the cross-sectional design of B-SNIP. We will use the B-SNIP battery with EP
participants in the context of Coordinated Specialty Care (CSC) treatment programs for EP
available at established B-SNIP sites. Our overall goal is to identify
biomarkers/Biotypes that predict clinical and functional outcome to CSC in EP. This
success could guide targeted interventions in CSC programs. For those unlikely to have a
successful CSC outcome, other targeted interventions could be developed and implemented.
We have active EP Clinics in the consortium; each will enter about16 patients/year,
80/year overall, providing 320 EP (schizophrenia, schizoaffective disorder, psychotic
bipolar disorder and schizophreniform disorder participants with approximately 240
completer cases, assuming 25% attrition) enrolled during the first 4 years of the
proposed funding period. All EP cases will be tested with B-SNIP biomarker assessments at
baseline, and the clinical and cognition assessments will be repeated at 1, 6, and 12
months. We will use an adapted version of the B-SNIP biomarker battery (called ADEPT)
which can be implemented in under-resourced, community settings.
SIGNIFICANCE AND BACKGROUND FOR THE STUDY Schizophrenia and related psychoses cause
enormous suffering for affected individual and their families and caregivers. They have a
lifetime prevalence of around 3%, and cost ~ $155 billion per year in direct healthcare
and indirect societal costs in the USA [5]. Relapse and poor response to treatment
contribute to a significant illness burden due to high rates of hospitalization and poor
social and occupational functioning. About 20% of early course psychosis (EP) cases
relapse in year 1, and about 40% by year 2 [6]. Mortality is increased four-fold in EP
compared to the general population [7]. EP outcomes are highly variable [8] with multiple
trajectories, i.e. episodic vs persistent, initial remission vs treatment resistance
[9-11]. Given this heterogeneity, actionable outcome predictors are needed to reliably
individualize care for EP [12].