Neurocognitive function as a possible marker for remission from clinical high risk for psychosis

Abstract

Background

Recent studies revealed that nonconverters at clinical high risk (CHR) for psychosis comprise those who later remit from initial CHR state and those who do not remit and continue to have attenuated positive symptoms. CHR subjects who remit symptomatically are comparable to healthy controls for both baseline and longitudinal symptoms. However, the neurocognitive characteristics of this population are still obscure.

Methods

Seventy-five CHR subjects and 61 healthy controls were recruited, and their neurocognitive functions were assessed. CHR subjects were divided into converter, remitter, and non-remitter groups according to their clinical state during a 12 to 24 month follow-up.

Results

Only the remitter group was comparable to healthy controls in terms of baseline neurocognitive functions. We observed that remitters showed better performance at baseline on tasks of attention, immediate/delayed verbal memory, verbal fluency, and immediate visual memory compared with converters. Moreover, we found that performance on semantic fluency was significantly improved in remitters but declined in non-remitters over the 2-year follow-up; however, there was no significant difference between these two groups at baseline.

Conclusion

CHR nonconverters who later remit from an initial prodromal state do not show reduced neurocognitive functioning compared with healthy controls at baseline. Therefore, an advanced research diagnostic criterion for a CHR state that considers neurocognitive functions is needed to more precisely predict which patients will develop psychosis.

Introduction

Over the last 15 years, the concept of “Ultra high risk (UHR)” or “Clinical high risk (CHR)” for psychosis has been developed. Recent studies have focused on identifying the predictors of transition to psychosis to develop optimal early intervention strategies (Fusar-Poli et al., 2013). However, recent evidence indicates that the rate of transition to psychosis has decreased from more than 50% to as low as 15% (Miller et al., 2002, Ziermans et al., 2011, Demjaha et al., 2012). Increased concerns have been raised that the remaining nonconverters may include a large number of false positives, leading to ethical issues regarding stigma and the adverse effects of pharmacotherapy for nonconverters (Liu and Demjaha, 2013). This phenomenon is thought to be due to earlier referral and effective early intervention (Yung et al., 2007). Another possible explanation is that more dilute samples are being recruited and that this dilution leads to more false positives. Several studies conducted in a healthy community population have indicated that psychotic-like experiences are common in the general population (van Os, 2003, Yung et al., 2009, Armando et al., 2010). Eliminating the false positives is crucial for detecting CHR individuals who later develop psychosis. However, the characteristics of the population that experiences an early remission from an initial CHR state are still obscure.

Neurocognitive deficits are the core of the pathophysiology of schizophrenia (Green et al., 2000, Mesholam-Gately et al., 2009). Likewise, recent meta-analytic studies indicated that CHR for psychosis is associated with significant and widespread impairment in neurocognitive functions (Fusar-Poli et al., 2012, Bora and Murray, 2013). Evidence from neuropsychological studies of CHR groups has suggested that cognitive deficits are present in the prodromal phase of psychosis, prior to the onset of illness. However, whether nonconverters and healthy individuals differ significantly in cognitive function is unclear due to mixed results over various cognitive domains. Nonconverters performed worse on task measuring executive function, spatial working memory, verbal memory, and verbal fluency (Becker et al., 2010, Kim et al., 2011). However, some studies found no significant differences between these two groups (Keefe et al., 2006, Seidman et al., 2010). This discrepancy may be attributable to the heterogeneity of the nonconverted CHR population, which consists of those still at risk and those who are false positives even though both groups present similar levels of prodromal symptoms.

CHR nonconverters comprise those who later remit from initial CHR state (remitters) and those who do not remit and continue to have attenuated positive symptoms (non-remitters) (Addington et al., 2011). Schlosser et al. (2012) indicated that CHR individuals who remitted symptomatically are similar to healthy controls for both baseline and longitudinal symptoms. Furthermore, among the neurocognitive functions, higher baseline immediate verbal memory is a predictor of remission from a CHR state (Simon et al., 2012). However, a number of unanswered questions remain. First, are there any baseline neurocognitive deficits in remitters compared with healthy controls? Second, what indicators discriminate remitters from non-remitters? Lastly, what is the trajectory of neurocognitive change in each subgroup over time?

In this study, we investigate the difference in cognitive functioning among converters, nonconverters without remission, and remitters and examine the trajectories of cognitive performance of each group over a 2-year follow-up. We hypothesize that individuals who remit from an initial CHR state will perform significantly better in neurocognitive function tests compared with those who later develop psychosis and that the remitters would show performance that is comparable to that of healthy controls on tasks involving neurocognitive functioning at baseline.