Frontal slow wave resting EEG power is higher in individuals at Ultra High Risk for psychosis than in healthy controls but is not associated with negative symptoms or functioning

Abstract Background Individuals at ultra-high risk for psychosis (UHR) present with subtle white matter alterations, which have been associated with clinical and functional outcome. The effect of cognitive remediation on white matter (WM) in UHR-individuals has not been investigated. Methods In a randomized, clinical intervention-trial (FOCUS), UHR-individuals aged 18–40 years were assigned to treatment as usual (TAU) or TAU plus cognitive remediation (CR) for 20 weeks. CR comprised 20 x 2-hour sessions of neurocognitive and social-cognitive training (SCIT). Primary outcome was whole brain fractional anisotropy (FA) derived from diffusion weighted imaging. Secondary outcomes pertained to regions of interest analyses. Planned post-hoc analyses explored dose-response effects of CR on WM. Main analyses of treatment effect of CR on primary and secondary outcomes were conducted using linear mixed models, assessing the interaction of timepoint by group (CR and TAU). Analyses were conducted according to the intention-to-treat principle. Results 111 UHR-individuals and 59 healthy controls were included. Attrition-rate was 30% at 6 months post-treatment follow-up. The CR group completed a mean of 12 hours of neurocognitive training. We found no effect of CR on whole-brain or regional FA. Planned post-hoc analyses revealed significant time*group (high- and low-attendance to CR) interactions in left superior corona radiata (p<0.01), left cingulum cingulate gyrus (P=0.03), and right superior longitudinal fasciculus (P<0,01), corrected. Specifically, when compared to UHR-individuals with high attendance (UHR-high >12 hours), those with low attendance (UHR-low <12 hours) had more co-morbid diagnoses, larger recreational smoking (nicotine and cannabis), more depressive and negative symptoms, and had significantly lower global FA at baseline, and showed a significant increase in FA after treatment. Furthermore, UHR-low displayed large effect-size (ES) improvements on depressive and negative symptoms, and moderate to large ES improvements in several cognitive functions (verbal fluency, verbal working memory, and processing speed). In contrast, UHR-high displayed large ES improvements in UHR-symptoms, and moderate ES improvement on social and occupational functioning. Discussion Contradicting our main hypothesis, we found no effect of CR on whole-brain or regional FA after six months. This may be explained by both the low number of neurocognitive training sessions and the attrition rate. The average of 12 hours of neurocognitive training is considerably lower than the recommended dosage of 25–30 hours necessary for cognitive improvements. The continuous need to develop feasible interventions and enhance adherence is stressed. Nevertheless, non-specific treatment may improve WM-integrity in UHR-individuals with lower global baseline FA in those with more severe psychopathology. The UHR-low subgroup exhibited improvements with large ES in levels of depressive and negative symptoms, as well as cognitive functions. We speculate, whether our results reflect that UHR-individuals with higher baseline FA (approaching the healthy controls), present with a preserved structural capacity for increased demands and new learning, while UHR-individuals characterized by lower FA at baseline may be more amendable to neuroplastic treatment-effects. The results support the value of subgrouping in a clinically heterogenous UHR-population, which also applies to examining WM integrity.

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Spatial working memory ability is a marker of risk-for-psychosis

Psychological Medicine ◽

10.1017/s0033291703008067 ◽

2003 ◽

Vol 33 (7) ◽

pp. 1239-1247 ◽

Cited By ~ 151

Author(s):

S. J. WOOD ◽

C. PANTELIS ◽

T. PROFFITT ◽

L. J. PHILLIPS ◽

G. W. STUART ◽

...

Keyword(s):

Working Memory ◽

High Risk ◽

Negative Symptoms ◽

Cognitive Deficit ◽

Spatial Working Memory ◽

Matching To Sample ◽

Healthy Controls ◽

Predictive Tool ◽

Ultra High Risk ◽

The Relationship

Background. Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients.Method. Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS).Results. Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P=0·02).Conclusions. Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.

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Effects of cannabis use on event related potentials in subjects at ultra high risk for psychosis and healthy controls

International Journal of Psychophysiology ◽

10.1016/j.ijpsycho.2013.03.012 ◽

2013 ◽

Vol 88 (2) ◽

pp. 149-156 ◽

Cited By ~ 10

Author(s):

Mirjam J. van Tricht ◽

Emma C. Harmsen ◽

Johannes H.T.M. Koelman ◽

Lo J. Bour ◽

Thérèse A. van Amelsvoort ◽

...

Keyword(s):

High Risk ◽

Event Related Potentials ◽

Cannabis Use ◽

Healthy Controls ◽

Ultra High Risk ◽

Related Potentials

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S150. EMOTIONAL BEHAVIOUR IN HIGH-RISK AND FIRST-EPISODE PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.216 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S93-S93

Author(s):

Irina Falkenberg ◽

Huai-Hsuan Tseng ◽

Gemma Modinos ◽

Barbara Wild ◽

Philip McGuire ◽

...

Keyword(s):

High Risk ◽

Emotion Recognition ◽

Psychotic Disorders ◽

First Episode Psychosis ◽

First Episode ◽

Healthy Controls ◽

Emotional Faces ◽

Facial Movements ◽

Episode Psychosis ◽

Ultra High Risk

Abstract Background Studies indicate that people with schizophrenia and first-episode psychosis experience deficits in their ability to accurately detect and display emotions through facial expressions, and that functioning and symptoms are associated with these deficits. This study aims to examine how emotion recognition and facial emotion expression are related to functioning and symptoms in a sample of individuals at ultra-high risk, first-episode psychosis and healthy controls. Methods During fMRI, we combined the presentation of emotional faces with the instruction to react with facial movements predetermined and assigned. 18 patients with first-episode psychosis (FEP), 18 individuals at ultra high risk of psychosis (UHR) and 22 healthy controls (HCs) were examined while viewing happy, sad, or neutral faces and were instructed to simultaneously move the corners of their mouths either (a). upwards or (b). downwards, or (c). to refrain from movement. The subjects’ facial movements were recorded with an MR-compatible video camera. Results Neurofunctional and behavioral response to emotional faces were measured. Analyses have only recently commenced and are ongoing. Full results of the clinical and functional impact of behavioral and neuroimaging results will be presented at the meeting. Discussion Increased knowledge about abnormalities in emotion recognition and behaviour as well as their neural correlates and their impact on clinical measures and functional outcome can inform the development of novel treatment approaches to improve social skills early in the course of schizophrenia and psychotic disorders.

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Relations of Self-Esteem with Paranoia in Healthy Controls, Individuals at Ultra-High Risk for Psychosis and with Recent Onset Schizophrenia

Korean Journal of Schizophrenia Research ◽

10.16946/kjsr.2013.16.2.86 ◽

2013 ◽

Vol 16 (2) ◽

pp. 86

Author(s):

Hui-Woo Yoon ◽

Yun Young Song ◽

Jee In Kang ◽

Suk Kyoon An

Keyword(s):

High Risk ◽

Self Esteem ◽

Healthy Controls ◽

Recent Onset ◽

Ultra High Risk

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Discriminative Analysis of Symptom Severity and Ultra-High Risk of Schizophrenia Using Intrinsic Functional Connectivity

International Journal of Neural Systems ◽

10.1142/s0129065720500471 ◽

2020 ◽

Vol 30 (09) ◽

pp. 2050047

Author(s):

Lubin Wang ◽

Xianbin Li ◽

Yuyang Zhu ◽

Bei Lin ◽

Qijing Bo ◽

...

Keyword(s):

High Risk ◽

Functional Connectivity ◽

Symptom Severity ◽

Large Scale ◽

Brain Networks ◽

Brain Regions ◽

Support Vector ◽

Healthy Controls ◽

Intrinsic Functional Connectivity ◽

Ultra High Risk

Past studies have consistently shown functional dysconnectivity of large-scale brain networks in schizophrenia. In this study, we aimed to further assess whether multivariate pattern analysis (MVPA) could yield a sensitive predictor of patient symptoms, as well as identify ultra-high risk (UHR) stage of schizophrenia from intrinsic functional connectivity of whole-brain networks. We first combined rank-based feature selection and support vector machine methods to distinguish between 43 schizophrenia patients and 52 healthy controls. The constructed classifier was then applied to examine functional connectivity profiles of 18 UHR individuals. The classifier indicated reliable relationship between MVPA measures and symptom severity, with higher classification accuracy in more severely affected schizophrenia patients. The UHR subjects had classification scores falling between those of healthy controls and patients, suggesting an intermediate level of functional brain abnormalities. Moreover, UHR individuals with schizophrenia-like connectivity profiles at baseline presented higher rate of conversion to full-blown illness in the follow-up visits. Spatial maps of discriminative brain regions implicated increases of functional connectivity in the default mode network, whereas decreases of functional connectivity in the cerebellum, thalamus and visual areas in schizophrenia. The findings may have potential utility in the early diagnosis and intervention of schizophrenia.

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Investigating Cognitive and Clinical Predictors of Real-Life Functioning, Functional Capacity, and Quality of Life in Individuals at Ultra-High Risk for Psychosis

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa027 ◽

2020 ◽

Vol 1 (1) ◽

Author(s):

Louise Birkedal Glenthøj ◽

Tina Dam Kristensen ◽

Christina Wenneberg ◽

Carsten Hjorthøj ◽

Merete Nordentoft

Keyword(s):

Quality Of Life ◽

Social Skills ◽

High Risk ◽

Functional Capacity ◽

Processing Speed ◽

Negative Symptoms ◽

Role Functioning ◽

Functional Impairments ◽

Ultra High Risk

Abstract A substantial proportion of individuals at ultra-high risk (UHR) for psychosis show long-term functional impairments, which may have profound consequences for the individual and society. Finding predictors of these functional impairments is critical to inform on the individual’s functional prognosis and potentially develop targeted interventions. This study used data from 91 UHR individuals participating in a randomized, clinical trial, that were followed up at 12 months, to elucidate on clinical, neuro- and social-cognitive predictors of UHR individuals’ functional outcome in the domains of social- and role functioning, quality of life, and functional capacity. The proportion of UHR individuals showing a poor social- and role outcome at 12-month follow-up was 50% and 63%, respectively. Worse social outcome was predicted by higher levels of negative symptoms, reduced processing speed, and impaired baseline social functioning explaining 52% of the variance. Worse role outcome was predicted by impaired role functioning at baseline, explaining 25% of the variance. Quality of life impairments were predicted by better theory of mind explaining 4% of the variance, and functional capacity social skills deficits were predicted by impaired baseline social skills explaining 20% of the variance. Our findings indicate that processing speed and negative symptoms may contribute to social- and role-functioning deficits, and while aspects of social cognition may also relate to social- and role functioning, baseline-functional impairments seem to be a strong contributor to persistent impairments in functioning and quality of life. If replicated, our findings suggest the need for future studies investigating the effect of pro-functional interventions targeting baseline functioning and targeted cognitive domains in UHR.

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