Various neurocognitive deficits and conversion risk in individuals at clinical high risk for psychosis.
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ABSTRACT: Aim
Individuals at clinical high risk for psychosis (CHR) exhibit neurocognitive deficits in multiple domains. The aim of this study is to investigate whether several components of neurocognition are predictive of conversion to psychosis.Methods
Fifty-two CHR individuals were assessed with the Structured Interview for Psychosis Risk Syndromes and completed a battery of neurocognitive tests at baseline including measures of executive functioning, attention, working memory, processing speed and reaction time. Neurocognitive functioning at baseline was scored based on an external normative control group. Most subjects were followed for 2.5 years to determine conversion status.Results
Significant differences in neurocognitive functioning between CHR individuals and the control group were present in all domains. Twenty-six per cent of the participants converted to psychosis within 9.8 (standard deviation = 8.0) months on average (median 9 months), but there were no significant differences in neurocognition converters and non-converters.Conclusions
Individuals at CHR have deficits in neurocognitive functioning, but such deficits do not appear to be related to conversion risk.
SUBMITTER: Mourik K
PROVIDER: S-EPMC5030118 | biostudies-literature | 2017 Jun
REPOSITORIES: biostudies-literature
Publications
Various neurocognitive deficits and conversion risk in individuals at clinical high risk for psychosis.
Mourik Kees K Decrescenzo Paula P Brucato Gary G Gill Kelly E KE Arndt Leigh L Kimhy David D Keilp John G JG Girgis Ragy R RR
Early intervention in psychiatry 20151210 3
<h4>Aim</h4>Individuals at clinical high risk for psychosis (CHR) exhibit neurocognitive deficits in multiple domains. The aim of this study is to investigate whether several components of neurocognition are predictive of conversion to psychosis.<h4>Methods</h4>Fifty-two CHR individuals were assessed with the Structured Interview for Psychosis Risk Syndromes and completed a battery of neurocognitive tests at baseline including measures of executive functioning, attention, working memory, process ...[more]
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Project description:BackgroundMetacognition refers to the ability to evaluate and control our cognitive processes. While studies have investigated metacognition in schizophrenia and clinical high risk for psychosis (CHR), less is known about the potential mechanisms which result in metacognitive deficits.AimsWe aimed to investigate whether neurocognitive functions including attention, working memory, verbal learning and executive functions predicted the tendency to focus on one's thoughts (cognitive self-consciousness) and beliefs in the efficacy of one's cognitive skills (cognitive confidence).MethodParticipants (130 CHR individuals) were recruited as part of the multi-site PREDICT study. They were assessed using the Metacognitions Questionnaire (MCQ) as well as measures of executive function (WCST), attention (N-Back), working memory (LNS) and verbal learning (AVLT).ResultsCognitive competence was negatively correlated with N-Back while cognitive self-consciousness was positively correlated with N-Back and LNS. Linear regression analysis with N-Back, AVLT, LNS and WCST as predictors showed that neurocognition significantly predicted cognitive self-consciousness, with N-Back, LNS and WCST as significant predictors. The model accounted for 14% of the variance in cognitive self-consciousness. However, neurocognition did not result in a significant predictive model of cognitive competence.ConclusionsNeurocognition was associated with an increased focus on one's thoughts, but it was not associated with higher confidence in one's cognitive skills. Neurocognition accounted for less than one-sixth of the variance in metacognition, suggesting that interventions that target neurocognition are unlikely to improve metacognitive abilities.
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Project description:ObjectivesIt is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP).MethodsTwenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed.ResultsThere were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP.ConclusionsOur study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.
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Project description:ImportanceNeurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined.ObjectiveTo provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P.Data sourcesWeb of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020.Study selectionMultistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P.Data extraction and synthesisIndependent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted.Main outcomes and measuresThe primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis.ResultsA total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = -1.17; 95% CI, -1.86 to -0.48), Hopkins Verbal Learning Test-Revised (g = -0.86; 95% CI, -1.43 to -0.28), digit symbol coding test (g = -0.74; 95% CI, -1.19 to -0.29), Brief Assessment of Cognition Scale Symbol Coding (g = -0.67; 95% CI, -0.95 to -0.39), University of Pennsylvania Smell Identification Test (g = -0.55; 95% CI, -0.97 to -0.12), Hinting Task (g = -0.53; 95% CI, -0.77 to -0.28), Rey Auditory Verbal Learning Test (g = -0.50; 95% CI, -0.78 to -0.21), California Verbal Learning Test (CVLT) (g = -0.50; 95% CI, -0.64 to -0.36), and National Adult Reading Test (g = -0.52; 95% CI, -1.01 to -0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = -0.58; 95% CI, -1.12 to -0.05). Meta-regressions found significant effects for age and education on processing speed.Conclusions and relevanceFindings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches.
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Project description:This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central Register of Reviews and Ovid/PsycINFO and trial registries up to July 1, 2020. The risk of bias was assessed using a modified version of the NOS for cohort and cross-sectional studies. Original studies reporting neurocognitive functioning in individuals at CHR-P compared to healthy controls (HC) or first-episode psychosis (FEP) patients were included. The primary outcome was the random-effect meta-analytic variability ratios (VR). Secondary outcomes included the coefficient of variation ratios (CVR). Seventy-eight studies were included, relating to 5162 CHR-P individuals, 2865 HC and 486 FEP. The CHR-P group demonstrated higher variability compared to HC (in descending order of magnitude) in visual memory (VR: 1.41, 95% CI 1.02-1.94), executive functioning (VR: 1.31, 95% CI 1.18-1.45), verbal learning (VR: 1.29, 95% CI 1.15-1.45), premorbid IQ (VR: 1.27, 95% CI 1.09-1.49), processing speed (VR: 1.26, 95% CI 1.07-1.48), visual learning (VR: 1.20, 95% CI 1.07-1.34), and reasoning and problem solving (VR: 1.17, 95% CI 1.03-1.34). In the CVR analyses the variability in CHR-P population remains in the previous neurocognitive domains and emerged in attention/vigilance, working memory, social cognition, and visuospatial ability. The CHR-P group transitioning to psychosis showed greater VR in executive functioning compared to those not developing psychosis and compared to FEP groups. Clinical high risk for psychosis subjects shows increased variability in neurocognitive performance compared to HC. The main limitation of this study is the validity of the VR and CVR as an index of variability which has received debate. This finding should be explored by further individual-participant data research and support precision medicine approaches.
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Project description:Study objectivesSleep spindles are waxing and waning EEG waves exemplifying the main fast oscillatory activity occurring during NREM sleep. Several recent studies have established that sleep spindle abnormalities are present in schizophrenia spectrum disorders, including in early-course and first-episode patients, and those spindle deficits are associated with some of the cognitive impairments commonly observed in these patients. Cognitive deficits are often observed before the onset of psychosis and seem to predict poor functional outcomes in individuals at clinical high-risk for psychosis (CHR). Yet, the presence of spindle abnormalities and their relationship with cognitive dysfunction has not been investigated in CHR.MethodsIn this study, overnight high-density (hd)-EEG recordings were collected in 24 CHR and 24 healthy control (HC) subjects. Spindle density, duration, amplitude, and frequency were computed and compared between CHR and HC. Furthermore, WM was assessed for both HC and CHR, and its relationship with spindle parameters was examined.ResultsCHR had reduced spindle duration in centro-parietal and prefrontal regions, with the largest decrease in the right prefrontal area. Moderation analysis showed that the relation between spindle duration and spindle frequency was altered in CHR relative to HC. Furthermore, CHR had reduced WM performance compared to HC, which was predicted by spindle frequency, whereas in HC spindle frequency, duration, and density all predicted working memory performance.ConclusionAltogether, these findings indicate that sleep spindles are altered in CHR individuals, and spindle alterations are associated with their cognitive deficits, thus representing a sleep-specific putative neurophysiological biomarker of cognitive dysfunction in psychosis risk.
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Project description:Motor deficits appear prior to psychosis onset, provide insight into vulnerability as well as mechanisms that give rise to emerging illness, and are predictive of conversion. However, to date, the extant literature has often targeted a complex abnormality (e.g., gesture dysfunction, dyskinesia), or a single fundamental domain (e.g., accuracy) but rarely provided critical information about several of the individual components that make up more complex behaviors (or deficits). This preliminary study applies a novel implicit motor task to assess domains of motor accuracy, speed, recognition, and precision in individuals at clinical high risk for psychosis (CHR-p). Sixty participants (29 CHR-p; 31 healthy volunteers) completed clinical symptom interviews and a novel Serial Interception Sequence Learning (SISL) task that assessed implicit motor sequence accuracy, speed, precision, and explicit sequence recognition. These metrics were examined in multilevel models that enabled the examination of overall effects and changes in motor domains over blocks of trials and by positive/negative symptom severity. Implicit motor sequence accuracy, speed, and explicit sequence recognition were not detected as impacted in CHR-p. When compared to healthy controls, individuals at CHR-p were less precise in motor responses both overall (d = 0.91) and particularly in early blocks which normalized over later blocks. Within the CHR-p group, these effects were related to positive symptom levels (t = - 2.22, p = 0.036), such that individuals with higher symptom levels did not improve in motor precision over time (r's = 0.01-0.05, p's > 0.54). CHR-p individuals showed preliminary evidence of motor precision deficits but no other motor domain deficits, particularly in early performance that normalized with practice.
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Project description:IntroductionClinical high risk for psychosis (CHR) is associated with mild cognitive impairments. Symptoms are clustered into positive, negative and disorganization symptoms. The association between specific symptom dimensions and cognitive functions remains unclear. The aim of this study was to investigate the associations between cognitive functions and positive, negative, and disorganization symptoms.Method53 CHR subjects fulfilling criteria for attenuated psychotic syndrome in the Structural Interview for Prodromal Syndromes (SIPS) were assessed for cognitive function. Five cognitive domain z-scores were defined by contrasting with observed scores of a group of healthy controls (n = 40). Principal Components Analyses were performed to construct general cognitive composite scores; one using all subtests and one using the cognitive domains. Associations between cognitive functions and symptoms are presented as Spearman's rank correlations and partial Spearman's rank correlations adjusted for age and gender.ResultsPositive symptoms were negatively associated with executive functions and verbal memory, and disorganization symptoms with poorer verbal fluency. Negative symptoms were associated with better executive functioning. There were no significant associations between the general cognitive composites and any of the symptom domains, except for a trend for positive symptoms.ConclusionIn line with previous research, data indicated associations between positive symptoms and poorer executive functioning. Negative symptoms may not be related to executive functions in CHR the same way as in psychosis. Our results could indicate that attenuated positive symptoms are more related to cognitive deficits in CHR than positive symptoms in schizophrenia and FEP.
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Project description:Memory deficits are a hallmark of psychotic disorders such as schizophrenia. However, whether the neural dysfunction underlying these deficits is present before the onset of illness and potentially predicts conversion to psychosis is unclear. In this study, we investigated brain functional alterations during memory processing in a sample of 155 individuals at clinical high risk (including 18 subjects who later converted to full psychosis) and 108 healthy controls drawn from the second phase of the North American Prodrome Longitudinal Study (NAPLS-2). All participants underwent functional magnetic resonance imaging with a paired-associate memory paradigm at the point of recruitment and were clinically followed up for approximately 2 years. We found that at baseline, subjects at high risk showed significantly higher activation during memory retrieval in the prefrontal, parietal, and bilateral temporal cortices (PFWE < .035). This effect was more pronounced in converters than nonconverters and was particularly manifested in unmedicated subjects (P < .001). The hyperactivation was significantly correlated with retrieval reaction time during scan in converters (P = .009) but not in nonconverters and controls, suggesting an exaggerated retrieval effort. These findings suggest that hyperactivation during memory retrieval may mark processes associated with conversion to psychosis, and such measures have potential as biomarkers for psychosis prediction.
| S-EPMC6581134 | biostudies-literature
Project description:BackgroundIn the early intervention in psychosis, ultra-high risk (UHR) criteria have been used to identify individuals who are prone to develop psychosis. Although the transition rate to psychosis in individuals at UHR is 10% to 30% within several years, some individuals at UHR present with poor prognoses even without transition occurring. Therefore, it is important to identify biomarkers for predicting the prognosis of individuals at UHR, regardless of transition. We investigated whether mismatch negativity (MMN) in response to both duration deviant stimuli (dMMN) and frequency deviant stimuli (fMMN) could predict prognosis, including remission and neurocognitive function in individuals at UHR.Materials and methodsIndividuals at UHR (n = 24) and healthy controls (HC; n = 18) participated in this study. In an auditory oddball paradigm, both dMMN and fMMN were measured at baseline. Remission and neurocognitive function after > 180 days were examined in the UHR group. Remission from UHR was defined as functional and symptomatic improvement using the Global Assessment of Functioning (GAF) score and Scale of Prodromal Symptoms (SOPS) positive subscales. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia (BACS). We examined differences in MMN amplitude at baseline between those who achieved remission (remitters) and those who did not (non-remitters). Multiple regression analyses were performed to identify predictors for functioning, positive symptoms, and neurocognitive function.ResultsCompared with the HC group, the UHR group had a significantly attenuated dMMN amplitude (p = 0.003). In the UHR group, GAF scores significantly improved during the follow-up period (mean value 47.1 to 55.5, p = 0.004). The dMMN amplitude at baseline was significantly larger in the remitter (n = 6) than in the non-remitter group (n = 18) (p = 0.039). The total SOPS positive subscale scores and fMMN amplitude at baseline could predict BACS attention subscore at the follow-up point (SOPS positive subscales, p = 0.030; fMMN, p = 0.041).ConclusionOur findings indicate that dMMN and fMMN predicted remission and neurocognitive function, respectively, in individuals at UHR, which suggests that there are both promising biomarker candidates for predicting prognosis in individuals at UHR.
| S-EPMC7416637 | biostudies-literature
Project description:IntroductionDisturbed sleep is a common feature of psychotic disorders that is also present in the clinical high risk (CHR) state. Evidence suggests a potential role of sleep disturbance in symptom progression, yet the interrelationship between sleep and CHR symptoms remains to be determined. To address this knowledge gap, we examined the association between disturbed sleep and CHR symptoms over time.MethodsData were obtained from the North American Prodrome Longitudinal Study (NAPLS)-3 consortium, including 688 CHR individuals and 94 controls (mean age 18.25, 46% female) for whom sleep was tracked prospectively for 8 months. We used Cox regression analyses to investigate whether sleep disturbances predicted conversion to psychosis up to >2 years later. With regressions and cross-lagged panel models, we analyzed longitudinal and bidirectional associations between sleep (the Pittsburgh Sleep Quality Index in conjunction with additional sleep items) and CHR symptoms. We also investigated the independent contribution of individual sleep characteristics on CHR symptom domains separately and explored whether cognitive impairments, stress, depression, and psychotropic medication affected the associations.ResultsDisturbed sleep at baseline did not predict conversion to psychosis. However, sleep disturbance was strongly correlated with heightened CHR symptoms over time. Depression accounted for half of the association between sleep and symptoms. Importantly, sleep was a significant predictor of CHR symptoms but not vice versa, although bidirectional effect sizes were similar.DiscussionThe critical role of sleep disturbance in CHR symptom changes suggests that sleep may be a promising intervention target to moderate outcome in the CHR state.
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