A longitudinal study of neurocognitive function in individuals at-risk for psychosis

INTRODUCTION: Clinically defined prodromal diagnostic criteria identify at-risk individuals with a 35-40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established. METHODS: A comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed. RESULTS: At-risk subjects performed more poorly than healthy subjects (t=2.93, P=0.01), but better than first episode subjects (t=4.72, p<0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N=11; z=-1.2), while those at-risk subjects who did not progress to psychosis (N=17) performed better (z=-0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis. CONCLUSION: Neurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

A longitudinal study of neurocognitive function in individuals at-risk for psychosis

IntroductionClinically defined prodromal diagnostic criteria identify at-risk individuals with a 35–40% likelihood of developing a psychotic disorder within a year. The time course and predictive value of cognitive deficits in the development of psychosis has not been established.MethodsA comprehensive neurocognitive battery and clinical assessments were administered to 37 subjects meeting Criteria of Prodromal States (COPS) criteria for being at risk for psychosis, and two comparison groups: 59 first episode and 47 healthy subjects. Subjects were also evaluated at 6-month and 1-year follow-up periods. Primary analyses used a neurocognitive composite score derived from individual neurocognitive measures, including measures of vigilance, verbal memory, working memory, and processing speed.ResultsAt-risk subjects performed more poorly than healthy subjects (t = 2.93, P = 0.01), but better than first episode subjects (t = 4.72, p < 0.0001). At-risk subjects were particularly impaired on measures of vigilance and processing speed. Cognitive composite scores were significantly lower in at-risk subjects who progressed to psychosis (N = 11; z = − 1.2), while those at-risk subjects who did not progress to psychosis (N = 17) performed better (z = − 0.5), and not significantly different from controls. Poor CPT performance combined with better WAIS-R digit symbol performance predicted progression to psychosis. Severity of neurocognitive deficits was not related to duration of prodrome or to time to development of psychosis and neurocognitive function improved in all subjects except those who progressed to psychosis.ConclusionNeurocognitive impairment emerges early in the course of psychotic illness. Performance on tests of neurocognition may prove to be an early risk predictor for subsequent development of psychotic disorders.     

Neurocognition in the Extended Psychosis Phenotype: Performance of a Community Sample of Adolescents With Psychotic Symptoms on the MATRICS Neurocognitive Battery

Neurocognitive dysfunction is well established in psychosis, but recent work suggests that processing speed deficits might represent a particularly important cognitive deficit. A number of significant confounds, however, such as disease chronicity and antipsychotic medication use, have been shown to affect processing speed, causing debate as to the core cognitive features of psychosis. We adopted a novel strategy of testing neurocognitive performance in the “extended psychosis phenotype,” involving community-based adolescents who are not clinically psychotic but who report psychotic symptoms and who are at increased risk of psychosis in adulthood. This allows investigation of the earliest cognitive factors associated with psychosis risk, while excluding potential confounds such as disease chronicity and antipsychotic use. A population sample of 212 school-going adolescents aged 11–13 years took part in this study. Psychotic symptoms were assessed using the psychosis section of the Schedule for Affective Disorders and Schizophrenia. Neurocognition was assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus neurocognitive battery. Adolescents with psychotic symptoms performed significantly more poorly on 3 processing speed tasks: Trail Making Test-A (F = 3.3, P < .05), Trail Making Test-B (F = 3.1, P < .05), and digit symbol coding task (F = 7.0, P < .001)—as well as on a nonverbal working memory (spatial span) task (F = 3.2, P < .05). Our findings support the idea that neurocognitive impairment, and processing speed impairment in particular, is a core feature of psychosis risk. This group likely demonstrates some of the earliest cognitive impairments associated with psychosis vulnerability.Key words: epidemiology/adolescents/cognitionKey words: epidemiology, adolescents, cognition     

Social cognition and neurocognition as independent domains in psychosis

Patients with psychosis display alterations in social cognition as well as in the realm of neurocognition. It is unclear, however, to what degree these cognitive domains represent two separate dimensions of liability or the pleiotropic expression of a single deficit. The purpose of the present study was to investigate (i) to what extent alterations in social cognition represent an independent area of vulnerability to psychosis, separate from neurocognitive deficits and (ii) whether social cognition is one construct or can be divided into several subcomponents. Five social cognition and three neurocognitive tasks were completed by 186 participants with different levels of vulnerability for psychosis: 44 patients with psychotic disorder; 47 subjects at familial risk; 41 subjects at psychometric risk and 54 control subjects. The social cognition tasks covered important basic subcomponents of social cognition, i.e. mentalisation (or theory of mind), data gathering bias (jumping to conclusions), source monitoring and attribution style. Neurocognitive tasks assessed speed of information processing, inhibition, cognitive shifting and strategy-driven retrieval from semantic memory. The results of factor analysis suggested that neurocognition and social cognition are two separate areas of vulnerability in psychosis. Furthermore, the social cognition measures lacked significant overlap, suggesting a multidimensional construct. Cognitive liabilities to psychosis are manifold, and include key processes underlying basic person-environment interactions in daily life, independent of cognition quantified by neuropsychological tests.     

Neurocognitive indicators for a conversion to psychosis: comparison of patients in a potentially initial prodromal state who did or did not convert to a psychosis

The study aims to identify potential neurocognitive indicators of an enhanced risk for developing psychosis. N=44 patients meeting clinical inclusion criteria for initial prodromal states (IPS) who developed psychosis within a median interval of 10 months were compared to N=39 IPS patients not developing psychosis within a minimum interval of 1 year (median 36 months), and to N=44 healthy controls on a comprehensive neuropsychological test battery (pattern recognition, divided and sustained attention, spatial and verbal working memory, verbal/visual memory, speed of processing, executive and intellectual functions). IPS patients who converted to psychosis performed worse than healthy controls on all broad neurocognitive domains. They were more impaired than IPS patients not developing psychosis on the Subject Ordered Pointing Task (SOPT; working memory), verbal memory functions, verbal executive, verbal IQ and speed of processing tests. After a Bonferroni-Holms adjustment for multiple testing differences on SOPT, Digit-Symbol Test, and verbal IQ remained significant (effect sizes d=0.54-0.88). Neurocognitive predictors had a sensitivity of 0.75 and a specificity of 0.79. Results support several cognitive domains as indicators of vulnerability to psychosis, and additionally suggest that subtle deficits in verbal abilities (working and long-term memory, executive and intellectual functions) and decreased speed of processing may help to predict conversion to psychosis in a clinically defined IPS group.     

Multivariate patterns of brain-cognition associations relating to vulnerability and clinical outcome in the at-risk mental states for psychosis

Background: Neuropsychological deficits are a core feature of established psychosis and have been previously linked to fronto‐temporo‐limbic brain alterations. Both neurocognitive and neuroanatomical abnormalities characterize clinical at‐risk mental states (ARMS) for psychosis. However, structure–cognition relationships in the ARMS have not been directly explored using multivariate neuroimaging techniques. Methods: Voxel‐based morphometry and partial least squares were employed to study system‐level covariance patterns between whole‐brain morphological data and processing speed, working memory, verbal learning/IQ, and executive functions in 40 ARMS subjects and 30 healthy controls (HC). The detected structure–cognition covariance patterns were tested for significance and reliability using non‐parametric permutation and bootstrap resampling. Results: We identified ARMS‐specific covariance patterns that described a generalized association of neurocognitive measures with predominantly prefronto‐temporo‐limbic and subcortical structures as well as the interconnecting white matter. In the conversion group, this generalized profile particularly involved working memory and verbal IQ and was positively correlated with limbic, insular and subcortical volumes as well as negatively related to prefrontal, temporal, parietal, and occipital cortices. Conversely, the neurocognitive profiles in the HC group were confined to working memory, learning and IQ, which were diffusely associated with cortical and subcortical brain regions. Conclusions: These findings suggest that the ARMS and prodromal phase of psychosis are characterized by a convergent mapping from multi‐domain neurocognitive measures to a set of prefronto‐temporo‐limbic and subcortical structures. Furthermore, a neuroanatomical separation between positive and negative brain–cognition correlations may not only point to a biological process determining the clinical risk for disease transition, but also to possible compensatory or dysmaturational neural processes. Hum Brain Mapp 33:2104–2124, 2012. © 2011 Wiley Periodicals, Inc.     

Neurocognitive deficits in the (putative) prodrome and first episode of psychosis

OBJECTIVE: International research programs have contributed to the creation of operationally defined criteria to identify individuals at risk for schizophrenia. Although there has been substantial progress in the prospective study of the schizophrenia prodrome, the utility of current diagnostic criteria remains questionable because of the relatively low base rates of incident psychoses, the high false-positive rate and ethical concerns regarding the treatment of individuals at risk. The identification of brain based neurocognitive vulnerability markers for schizophrenia may contribute to the development of an at risk algorithm with greater predictive accuracy. METHODS: Forty subjects at risk (AR) for schizophrenia, 15 in their first episode (FE) of schizophrenia, and 36 healthy comparison (HC) subjects were administered a neurocognitive battery that assessed the domains of processing speed, working memory, verbal episodic memory, executive functioning and general intelligence. RESULTS: At baseline, AR subjects showed neurocognitive deficits across all domains compared to HC subjects that were less severe than those observed in the FE sample. In preliminary analyses, AR subjects who later converted to psychosis (N=5) had greater neurocognitive impairment at baseline evaluation compared to those individuals who remained "at risk" at follow-up. CONCLUSIONS: Neurocognitive deficits may be important in the pathogenesis of early psychosis and could help to define individuals at greatest risk for schizophrenia. Continued research in larger cohorts is needed to test the validity of this neurocognitive profile and its utility as a vulnerability marker.     

Neuropsychological Profiles in Different At-Risk States of Psychosis: Executive Control Impairment in the Early—and Additional Memory Dysfunction in the Late—Prodromal State

Impairments in neuropsychological functioning have been described in subjects clinically at high risk for psychosis, but the specific cognitive deficits in different clinical high-risk groups remain to be elucidated. The German Research Network on Schizophrenia employs a heuristic 2-stage model: a putatively late prodromal state (LPS), characterized by the onset of attenuated positive or brief psychotic symptoms, and an early prodromal state (EPS), mainly characterized by the presence of basic symptoms, which are predictive for psychosis within the next 10 years.A total of 205 subjects met the criteria for either an EPS or an LPS of psychosis and were assessed with a comprehensive neuropsychological test battery. Neurocognitive profiles of high-risk groups were compared with data of 87 healthy controls comparable with regard to gender, age, and premorbid verbal IQ.Patients in the LPS were impaired in all neurocognitive domains (memory/learning, executive control/processing speed, and working memory) examined, with memory being the worst. Deficits were less pronounced in patients in the EPS, with a specific deficit in the executive control/processing speed domain. Consistent with a progressive neurodevelopmental disorder, some cognitive abilities were already impaired in patients in the EPS, followed by further deterioration in the LPS. Specifically, deficits in executive control functioning were related to the presence of basic symptoms, indicating a vulnerability for psychosis. Memory deficits were associated with the onset of psychotic symptoms indicating further disease progression in the trajectory to psychosis and, thus, may be useful in predicting psychosis and targeting early intervention.     

Social Cognition Deficits Among Individuals at Familial High Risk for Schizophrenia

Social cognition in young relatives of schizophrenia probands (N = 70) and healthy controls (N = 63) was assessed using the Penn Emotion Recognition Test-40 to examine the presence of social cognitive deficits in individuals at risk for the disorder. Measures of neurocognitive function and prodromal psychopathology were collected to assess the cognitive and clinical correlates of social cognitive impairments in at-risk relatives. Results indicated that when compared with healthy controls, individuals at familial high risk for schizophrenia were significantly more likely to overattribute emotions to neutral faces, with such individuals frequently misinterpreting neutral faces as negative. In addition, at-risk individuals had significantly greater reaction times when completing emotion recognition tasks, regardless of valence. Impairments in neurocognition were largely independent of social cognitive performance, and emotion recognition impairments persisted after adjusting for deficits in neurocognitive function. Further, social cognitive impairments in the interpretation of neutral faces were significantly associated with greater positive and general prodromal psychopathology, whereas neurocognitive impairments were only associated with disorganization. These results suggest that impairments in social cognition may be unique endophenotypes for schizophrenia.     

Early recognition and disease prediction in the at-risk mental States for psychosis using neurocognitive pattern classification

Background: Neuropsychological deficits predate overt psychosis and overlap with the impairments in the established disease. However, to date, no single neurocognitive measure has shown sufficient power for a prognostic test. Thus, it remains to be determined whether multivariate neurocognitive pattern classification could facilitate the diagnostic identification of different at-risk mental states (ARMS) for psychosis and the individualized prediction of illness transition. Methods: First, classification of 30 healthy controls (HC) vs 48 ARMS individuals subgrouped into 20 "early," 28 "late" ARMS subjects was performed based on a comprehensive neuropsychological test battery. Second, disease prediction was evaluated by categorizing the neurocognitive baseline data of those ARMS individuals with transition (n = 15) vs non transition (n = 20) vs HC after 4 years of follow-up. Generalizability of classification was estimated by repeated double cross-validation. Results: The 3-group cross-validated classification accuracies in the first analysis were 94.2% (HC vs rest), 85.0% (early at-risk subjects vs rest), and, 91.4% (late at-risk subjects vs rest) and 90.8% (HC vs rest), 90.8% (converters vs rest), and 89.0% (nonconverters vs rest) in the second analysis. Patterns distinguishing the early or late ARMS from HC primarily involved the verbal learning/memory domains, while executive functioning and verbal IQ deficits were particularly characteristic of the late ARMS. Disease transition was mainly predicted by executive and verbal learning impairments. CONCLUSIONS: Different ARMS and their clinical outcomes may be reliably identified on an individual basis by evaluating neurocognitive test batteries using multivariate pattern recognition. These patterns may have the potential to substantially improve the early recognition of psychosis.     

Neurocognitive Dysfunction in Bipolar and Schizophrenia Spectrum Disorders Depends on History of Psychosis Rather Than Diagnostic Group

Objectives: Neurocognitive dysfunction is milder in bipolar disorders than in schizophrenia spectrum disorders, supporting a dimensional approach to severe mental disorders. The aim of this study was to investigate the role of lifetime history of psychosis for neurocognitive functioning across these disorders. We asked whether neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends more on history of psychosis than diagnostic category or subtype. Methods: A sample of individuals with schizophrenia (n = 102), schizoaffective disorder (n = 27), and bipolar disorder (I or II) with history of psychosis (n = 75) and without history of psychosis (n = 61) and healthy controls (n = 280), from a large ongoing study on severe mental disorder, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery. Results: Compared with controls, all 3 groups with a history of psychosis performed poorer across neurocognitive measures, while the bipolar group without a history of psychosis was only impaired on a measure of processing speed. The groups with a history of psychosis did not differ from each other but performed poorer than the group without a history of psychosis on a number of neurocognitive measures. These neurocognitive group differences were of a magnitude expected to have clinical significance. In the bipolar sample, history of psychosis explained more of the neurocognitive variance than bipolar diagnostic subtype. Conclusions: Our findings suggest that neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders is determined more by history of psychosis than by Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnostic category or subtype, supporting a more dimensional approach in future diagnostic systems.     

Distinguishing Prodromal From First-Episode Psychosis Using Neuroanatomical Single-Subject Pattern Recognition

Background: The at-risk mental state for psychosis (ARMS) and the first episode of psychosis have been associated with structural brain abnormalities that could aid in the individualized early recognition of psychosis. However, it is unknown whether the development of these brain alterations predates the clinical deterioration of at-risk individuals, or alternatively, whether it parallels the transition to psychosis at the single-subject level. Methods: We evaluated the performance of an magnetic resonance imaging (MRI)-based classification system in classifying disease stages from at-risk individuals with subsequent transition to psychosis (ARMS-T) and patients with first-episode psychosis (FE). Pairwise and multigroup biomarkers were constructed using the structural MRI data of 22 healthy controls (HC), 16 ARMS-T and 23 FE subjects. The performance of these biomarkers was measured in unseen test cases using repeated nested cross-validation. Results: The classification accuracies in the HC vs FE, HC vs ARMS-T, and ARMS-T vs FE analyses were 86.7%, 80.7%, and 80.0%, respectively. The neuroanatomical decision functions underlying these discriminative results particularly involved the frontotemporal, cingulate, cerebellar, and subcortical brain structures. Conclusions: Our findings suggest that structural brain alterations accumulate at the onset of psychosis and occur even before transition to psychosis allowing for the single-subject differentiation of the prodromal and first-episode stages of the disease. Pattern regression techniques facilitate an accurate prediction of these structural brain dynamics at the early stage of psychosis, potentially allowing for the early recognition of individuals at risk of developing psychosis.Key words: at-risk mental state, early prediction of psychosis, voxel-based morphometry, multivariate analysis, machine learning, support vector machine     

Elevated Antisaccade Error Rate as an Intermediate Phenotype for Psychosis Across Diagnostic Categories

Background: Elevated antisaccade error rate, reflecting problems with inhibitory behavioral control, is a promising intermediate phenotype for schizophrenia. Here, we consider whether it marks liability across psychotic disorders via common or different neurophysiological mechanisms and whether it represents a neurocognitive risk indicator apart from the generalized cognitive deficit. Methods: Schizophrenia (n = 267), schizoaffective (n = 150), and psychotic bipolar (n = 202) probands, their first-degree relatives (ns = 304, 193, 242, respectively), and healthy controls (n = 244), participating in the Bipolar-Schizophrenia Network on Intermediate Phenotypes consortium, performed antisaccade and prosaccade tasks and completed a neuropsychological battery. Results: Antisaccade error rate was elevated in proband groups with greatest deficit observed in schizophrenia and was unrelated to symptoms and antipsychotic treatment. Increased error rate was also observed among relatives, even those without history of psychosis or psychosis spectrum personality traits. Relatives’ deficits were similar across proband diagnoses. Error rate was familial and remained elevated in proband and relative groups after accounting for generalized cognitive impairment. Speed of attentional shifting, indexed by prosaccade latency, was similarly influenced in all groups by manipulations that freed vs increasingly engaged attention systems and was inversely associated with antisaccade error rate in all but schizophrenia probands. Conclusions: These findings indicate that elevated antisaccade error rate represents an intermediate phenotype for psychosis across diagnostic categories, and that it tracks risk beyond that attributable to the generalized cognitive deficit. The greater severity of antisaccade impairment in schizophrenia and its independence from attention shifting processes suggest more severe and specific prefrontal inhibitory control deficits in this disorder.Key words: schizophrenia, schizoaffective disorder, bipolar disorder, endophenotype, family study     

The nature and consequences of cognitive deficits among tobacco smokers with HIV: a comparison to tobacco smokers without HIV

HIV-infected smokers lose more years of life to tobacco-related disease than HIV. Since neurocognitive deficits are common among those with HIV and are associated with smoking persistence, these deficits may be a unique barrier to smoking cessation among HIV-infected smokers. Documenting unique differences in and correlates of cognition among HIV-infected smokers is a critical step towards developing a population-specific tobacco cessation treatment. We compared neurocognitive function between HIV-infected (n = 103) and HIV-uninfected smokers (n = 70), accounting for demographic and smoking-related variables. We also evaluated whether HIV-related health outcomes (e.g., CD4 count, viral load, depression ratings, quality of life [QoL]) and HAART adherence were associated with cognition. Participants completed neurocognitive tasks (N-back and Continuous Performance Task [CPT]) measuring working memory, attention, and processing speed, and intra-individual variability. Stepwise regression models were conducted and validated with resampling techniques. HIV-infected smokers performed worse than HIV-uninfected smokers on working memory, processing speed, and intra-individual variability (all p < 0.01). ROC analysis for the model including cognitive measures demonstrated 85% area under the curve, which indicates “good prediction” for distinguishing between HIV-infected and HIV-uninfected smokers. This was a significant improvement over the model including demographic and smoking-related variables only (p = 0.0003). Among HIV-infected smokers, neurocognitive performance was negatively associated with QoL and depression ratings. Smoking cessation interventions for HIV-infected smokers should consider cognitive neurorehabilitation as a potential strategy to decrease the likelihood of nicotine relapse and decrease tobacco-related morbidity in this population.     

Psychosis Prediction: Stratification of Risk Estimation With Information-Processing and Premorbid Functioning Variables

Background: The period preceding the first psychotic episode is regarded as a promising period for intervention. We aimed to develop an optimized prediction model of a first psychosis, considering different sources of information. The outcome of this model may be used for individualized risk estimation. Methods: Sixty-one subjects clinically at high risk (CHR), participating in the Dutch Prediction of Psychosis Study, were assessed at baseline with instruments yielding data on neuropsychology, symptomatology, environmental factors, premorbid adjustment, and neurophysiology. The follow-up period was 36 months. Results: At 36 months, 18 participants (29.5%) had made a transition to psychosis. Premorbid adjustment (P = .001, hazard ratio [HR] = 2.13, 95% CI = 1.39/3.28) and parietal P300 amplitude (P = .004, HR = 1.27, 95% CI = 1.08/1.45) remained as predictors in the Cox proportional hazard model. The resulting prognostic score (PS) showed a sensitivity of 88.9% and a specificity of 82.5%. The area under the curve of the PS was 0.91 (95% CI = 0.83–0.98, cross-validation: 0.86), indicating an outstanding ability of the model to discriminate between transition and nontransition. The PS was further stratified into 3 risk classes establishing a prognostic index. In the class with the worst social-personal adjustment and lowest P300 amplitudes, 74% of the subjects made a transition to psychosis. Furthermore, transition emerged on average more than 17 months earlier than in the lowest risk class. Conclusions: Our results suggest that predicting a first psychotic episode in CHR subjects could be improved with a model including premorbid adjustment and information-processing variables in a multistep algorithm combining risk detection and stratification.Key words: clinical high risk, psychosis prediction, P300 event-related potential, premorbid adjustment, prognostic index     

Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

Objective: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. Method: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. Results: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. Conclusions: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention.     

Cognition in children and young adults with myoclonus dystonia – A case control study

IntroductionIn adult patients with myoclonus dystonia (MD), cognitive deficits regarding information processing speed and executive functioning have been demonstrated, but it is unclear whether cognition is also affected in young MD patients. The present study investigates cognition in young MD patients and the role of an SGCE mutation.MethodsIn this case control study 20 young MD patients (9 children (5.75–12.58 years) and 11 adolescents/young adults (13.5–25.42 years)) were included and compared to an age-, IQ- and gender-matched healthy control group (n = 40). Within the patient group, we compared patients with (n = 12) and without (n = 8) an SGCE mutation (SGCE+/-). All participants completed neuropsychological tests for memory, attention/processing speed, executive functioning, social cognition and language.ResultsOverall, patients performed in the (low) average range, comparable to healthy controls. Only on a semantic fluency test, patients scored significantly lower. SGCE + patients had lower emotion recognition scores (a social cognition test) compared to SGCE-patients.ConclusionWe could not demonstrate cognitive deficits as found in adult MD patients in our younger group. Patients performed on the same level as healthy controls, with only a small difference in semantic fluency. We did not find executive deficits that were manifest in adult SGCE + patients, but we did find an association of an SGCE mutation and lower scores on a social cognition test. Similar to executive functioning, social cognition is a prefrontally regulated function, but had not been tested in adult MD. Hence, social cognition may precede executive problems in adulthood, suggesting growing into deficit.     

The course of neurocognition and social functioning in individuals at ultra high risk for psychosis

OBJECTIVE: This study evaluates longitudinal neuropsychological performance and its association with clinical symptomatology and psychosocial outcome in individuals identified as ultra high risk (UHR) for psychosis. METHODS: Thirty-five UHR individuals completed neurocognitive, clinical, and social/role functioning assessments at baseline and, on average, 8.3 months later. RESULTS: UHR subjects showed significant cognitive deficits at baseline and 2 distinct profiles of cognitive change over time. On average, 50% demonstrated improvement in social and role functioning over the follow-up period, while the other half showed either stability or decline in functioning. Functional improvement was associated with improved processing speed and visual memory, as well as improvement in clinical symptoms over the follow-up period. In contrast, patients who did not improve functionally showed stable clinical symptoms and cognitive performance over time. CONCLUSIONS: Although the degree of neurocognitive deficit at baseline in UHR patients does not predict psychosocial outcome, the course of neurocognitive change over the first 8 months of follow-up does differentiate patients with good and poor functional outcomes.     

Neurocognitive predictors of functional outcome two to 13 years after identification as ultra-high risk for psychosis

Background and aim

Little is known about the relationship between neurocognitive performance and functional outcome before the onset of frank psychosis. This longitudinal study aimed to investigate neurocognitive predictors of poor functional outcome in a group identified as ultra-high risk (UHR) for psychosis between two and 13 years prior.

Method

Individuals (N = 230) identified as UHR for psychosis at the PACE Clinic in Melbourne completed assessment of psychopathology, functioning and neurocognition at baseline and follow-up. The mean length of follow-up was 7.26 years (SD 3.05).

Results

Forty-one individuals with the poorest functional outcome were identified. Only 48.8% of this group had transitioned to psychosis. Poor functional outcome was associated with reduced performance at baseline in the specific neurocognitive domains of verbal learning and memory, processing speed and attention, and verbal fluency, but not global cognitive impairment. Reduced performance on a verbal story recall task, in combination with higher negative symptoms at baseline, was the best predictor of later poor outcome. Baseline positive psychotic symptoms and GAF scores were not associated with later poor outcome.

Discussion

To date, this is the longest follow-up study of an UHR sample. Poor functional outcome was associated with specific neurocognitive decrements, regardless of transition to psychosis. The detection of individuals with poor functioning at follow-up, against a background of previously identified risk factors for psychotic disorder, may yield a valid group in which to study biomarkers and treatment of schizophrenia.     

Risk for Bipolar Disorder Is Associated With Face-Processing Deficits Across Emotions

ObjectiveYouths with euthymic bipolar disorder (BD) have a deficit in face-emotion labeling that is present across multiple emotions. Recent research indicates that youths at familial risk for BD, but without a history of mood disorder, also have a deficit in face-emotion labeling, suggesting that such impairments may be an endophenotype for BD. It is unclear whether this deficit in at-risk youths is present across all emotions or if the impairment presents initially as an emotion-specific dysfunction that then generalizes to other emotions as the symptoms of BD become manifest.MethodThirty-seven patients with pediatric BD, 25 unaffected children with a first-degree relative with BD, and 36 typically developing youths were administered the Emotional Expression Multimorph Task, a computerized behavioral task, which presents gradations of facial emotions from 100% neutrality to 100% emotional expression (happiness, surprise, fear, sadness, anger, and disgust).ResultsRepeated-measures analysis of covariance revealed that, compared with the control youths, the patients and the at-risk youths required significantly more intense emotional information to identify and correctly label face emotions. The patients with BD and the at-risk youths did not differ from each other. Group-by-emotion interactions were not significant, indicating that the group effects did not differ based on the facial emotion.ConclusionsThe youths at risk for BD demonstrate nonspecific deficits in face-emotion recognition, similar to patients with the illness. Further research is needed to determine whether such deficits meet all the criteria for an endophenotype. J. Am. Acad. Child Adolesc. Psychiatry, 2008;47(12):1455–1461.