Longitudinal change in neurocognition and its relation to symptomatic and functional changes over 2years in individuals at clinical high-risk for psychosis.

BACKGROUND: Negative symptoms and functional disability represent the core of schizophrenia and both are associated with cognitive impairments. We explored the course of cognitive change and its relation to symptomatic and functional changes in individuals at clinical high-risk (CHR) for psychosis to identify cognitive indicators of long-term course. Such attempts may offer insight into the pathological changes associated with the development of illness in the prodromal state. METHODS: Forty-seven CHR individuals completed neurocognitive, clinical, and functional assessments at baseline and 2-year follow-up; twenty-eight healthy controls were assessed for neurocognitive and functional measures at baseline and 2-year follow-up. The delta values of CHR individuals in neurocognitive, clinical, and functional domains were determined from differences between baseline and follow-up scores to estimate the degree of change. RESULTS: Although overall longitudinal cognitive performance of CHR individuals improved, the magnitude of improvement was not statistically different from that of normal controls at the group level. However, the individual data yielded two groups of CHR subjects showing opposite trajectories of cognitive change in semantic fluency (i.e., improvement or decline), which was significantly associated with changes in negative symptoms and functioning. Moreover, the relationships between negative symptoms and functioning were more strengthened over time than baseline. CONCLUSIONS: Our findings show that semantic fluency seems to be a neurocognitive indicator reflecting clinical courses in CHR individuals. The longitudinal relationship of negative symptoms and functioning with semantic fluency may represent ongoing pathological processes in neural systems involving aberrant fronto-temporal interaction in the early phase of schizophrenia.

Correction: Increased Intra-Individual Variability of Cognitive Processing in Subjects at Risk Mental State and Schizophrenia Patients.

[This corrects the article DOI: 10.1371/journal.pone.0078354.].

Decreased neural response for facial emotion processing in subjects with high genetic load for schizophrenia.

BACKGROUND: Patients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. METHODS: Block design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16-35, and 17 age, sex, and education year-matched healthy controls (HC). During the facial emotional processing for fearful, happy, and neutral face stimuli, participants were asked to explicitly determine the gender per stimuli. RESULTS: Occipito-temporo-limbic area in fearful face condition and involvement of broader region including prefrontal cortex in neutral face condition revealed significant attenuation of BOLD signal activation in GHR compared to HC. The GHR demonstrated less activity in right amygdala during fearful and neutral face condition. CONCLUSION: The study presented that GHR displayed abnormal brain activity in occipito-temporo-limbic-frontal network implicated in facial emotion processing. It indicates that abnormal facial emotion processing may be influenced by a genetic factor and could be a trait marker in schizophrenia.

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

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 24month 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.

General intellectual functioning as a buffer against theory-of-mind deficits in individuals at ultra-high risk for psychosis.

The influence of neurocognition, including general intelligence, on theory of mind (ToM) among patients with schizophrenia spectrum disorder is controversial. The purpose of the present study was to identify the influences of the non-ToM cognition and general intelligence on ToM performance in individuals at ultra-high risk (UHR) for psychosis. Fifty-five UHR subjects and 58 healthy controls (HCs) completed neurocognitive, verbal, and nonverbal ToM tasks. UHR individuals showed poorer performance in the two verbal ToM tasks, the false-belief task and the strange-story tasks. Moreover, the UHR subjects displayed poorer recall on the interference list of the verbal learning test. Linear regression analysis revealed that neurocognitive functioning, including executive functioning, working memory, and general intelligence, accounted for significant amounts of the variance in the results for UHR individuals: 20.4% in the false-belief task, 44.0% in the strange-story task, and 49.0% in the nonverbal cartoon task. Neurocognition, including general intelligence, was not a significant contributor to performance on ToM tasks in HCs. ToM deficits were not noted in UHR individuals with above-average IQ scores (≥ 110) compared with UHR subjects with IQ scores less than 110, who displayed significant differences on all ToM tasks compared with HCs. The present results suggest that ToM deficits in UHR individuals are complex and may be influenced by non-ToM cognition. Our findings are discussed in relation to the role of neurocognitive abilities in ToM-related impairments in UHR individuals.

Increased intra-individual variability of cognitive processing in subjects at risk mental state and schizophrenia patients.

Intra-individual variability (IIV) has received recent attention as an indicator of the stability of cognitive functioning that may outperform mean performance in reflecting putative neurobiological abnormalities. Increased IIV is regarded as a core deficit in schizophrenia patients; however, whether this deficit is present in the prodromal phase before the onset of schizophrenia has not been well established. In the present study, we investigated IIV using the stop-signal paradigm in at-risk mental state (ARMS) individuals and in schizophrenia patients. The study included 27 ARMS subjects, 37 schizophrenia patients, and 38 normal controls. The stop-signal task was administered to assess IIV and response inhibition. IIV was estimated by calculating the standard deviation across sub-blocks for the three groups. We observed increased IIV in ARMS subjects and schizophrenia patients compared with normal controls in both the "stop" and the "go" processes even though the mean response inhibition performances were not impaired in the ARMS group. Schizophrenia patients showed impaired response inhibition that was associated with the severity of negative symptoms. Our findings suggest that the analysis of IIV may identify cognitive and clinical features of ARMS that are not detectable by conventional mean performance analysis. The unstable response patterns associated with ARMS may originate from abnormal processing in neural systems caused by alterations in the integrity of functional brain networks and dopamine neuromodulation.