Widening the net: Use of social media data in personal injury and disability evaluations.

A central tenet of forensic mental health assessment is the use of multiple sources of data. Traditionally, these sources have included clinical interviews with and observations of the examinee, written records review, psychological test data, and interviews with collateral sources. Data from social media and social networking sites (SNS) is now widely used in civil litigation. However, existing professional practice standards and guidelines do not specifically address the use of SNS data. This leaves forensic mental health evaluators with little guidance as to why, when and how to incorporate SNS data into their evaluations. We review the extant literature on the use of SNS and other social media data in personal injury and disability cases, including legal, ethical, and practical considerations, with the goal of providing forensic mental health practitioners with a framework for making decisions about when and how to incorporate these data into their evaluations and opinions. We advocate caution in conducting independent searches of social media and the Internet, and in making inferences about internal states based on SNS postings. To illustrate these points, we include a case study.

The magnitude and variability of neurocognitive performance in first-episode psychosis: a systematic review and meta-analysis of longitudinal studies.

Neurocognitive deficits are a core feature of psychotic disorders, but it is unclear whether they affect all individuals uniformly. The aim of this systematic review and meta-analysis was to synthesize the evidence on the magnitude, progression, and variability of neurocognitive functioning in individuals with first-episode psychosis (FEP). A multistep literature search was conducted in several databases up to November 1, 2022. Original studies reporting on neurocognitive functioning in FEP were included. The researchers extracted the data and clustered the neurocognitive tasks according to the seven Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and six additional domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted. The primary effect size reported was Hedges g of (1) neurocognitive functioning in individuals at FEP measuring differences with healthy control (HC) individuals or (2) evolution of neurocognitive impairment across study follow-up intervals. Of 30,384 studies screened, 54 were included, comprising 3,925 FEP individuals and 1,285 HC individuals. Variability analyses indicated greater variability in FEP compared to HC at baseline and follow-up. We found better neurocognitive performance in the HC group at baseline and follow-up but no differences in longitudinal neurocognitive changes between groups. Across the 13 domains, individuals with FEP showed improvement from baseline in all studied domains, except for visual memory. Metaregressions showed some differences in several of the studied domains. The findings suggest that individuals with FEP have marked cognitive impairment, but there is greater variability in cognitive functioning in patients than in HC. This suggests that subgroups of individuals suffer severe disease-related cognitive impairments, whereas others may be much less affected. While these impairments seem stable in the medium term, certain indicators may suggest potential further decline in the long term for a specific subgroup of individuals, although more research is needed to clarify this. Overall, this study highlights the need for tailored neurocognitive interventions for individuals with FEP based on their specific deficits and progression.

Longitudinal change in neurocognitive functioning in children and adolescents at clinical high risk for psychosis: a systematic review.

Clinical high risk of psychosis (CHR-P) population has become an attractive area of interest in preventing transitions to psychosis. The consequences of developing a psychotic disorder may be worse in cases of early onset. Thus, childhood and adolescence represent a critical developmental window, where opportunities to gain social and adaptive abilities depend on the individuals' neurocognitive performance. There have been previous syntheses of the evidence regarding neurocognitive functioning in CHR-P individuals and its longitudinal changes. However, there has been less focus on children and adolescents at CHR-P. A multistep literature search was performed from database inception until July 15th, 2022. PRIMSA/MOOSE compliant systematic review and PROSPERO protocol were used to identify studies reporting on longitudinal changes in neurocognitive functioning in children and adolescents (mean age of sample ≤ 18 years) at CHR-P and matched healthy control (HC) group. A systematic review of identified studies was then undertaken. Three articles were included, resulting in a total sample size of 151 CHR-P patients [mean (SD) age, 16.48 (2.41) years; 32.45% female] and 64 HC individuals [mean (SD) age, 16.79 (2.38) years; 42.18% female]. CHR-P individuals had worse outcomes in verbal learning, sustained attention and executive functioning domains compared to HC. Individuals taking antidepressants had better outcomes in verbal learning in contrast with those taking antipsychotics. In children and adolescents, neurocognition may be already impaired before the psychosis onset, and remains stable during the transition to psychosis. Further study should be performed to obtain more robust evidence.

Brain structural abnormalities of the associative striatum in adolescents and young adults at genetic high-risk of schizophrenia: Implications for illness endophenotypes.

OBJECTIVE: Dysfunction in cortico-striatal circuitry represents a core component of the pathophysiology in schizophrenia (SZ) but its potential as a candidate endophenotype of the illness is often confounded by neuroleptic medication. METHODS: Accordingly, 26 adolescent and young adult participants at genetic high-risk for schizophrenia, but who were asymptomatic and neuroleptic naïve, and 28 age-matched controls underwent 1.5T structural magnetic resonance imaging of the striatum, manually parcellated into limbic (LST), associative (AST), and sensorimotor (SMST) functional subregions. RESULTS: In relation to their age peers, participants at genetic high-risk for schizophrenia showed overall lower striatal gray matter volume with their most pronounced loss, bilaterally in the AST, but not the LST or SMST. Neuropsychological testing revealed reduced executive functioning for genetically at-risk participants, although the groups did not differ significantly in overall intelligence or oral reading. For controls but not for at-genetic high-risk participants, stronger executive functioning correlated with increased bilateral AST volume. CONCLUSIONS: Reduced bilateral AST volume in genetic high-risk adolescents and young adults, accompanied by heritable loss of higher cognitive brain-behavior relationships, might serve as a useful endophenotype of SZ.

Examining the variability of neurocognitive functioning in individuals at clinical high risk for psychosis: a meta-analysis.

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.

Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis.

IMPORTANCE: Neurocognitive 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. OBJECTIVE: To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P. DATA SOURCES: Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020. STUDY SELECTION: Multistep 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 SYNTHESIS: Independent 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 MEASURES: The 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. RESULTS: A 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 RELEVANCE: Findings 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.

Cognitive dysfunction in a psychotropic medication-naïve, clinical high-risk sample from the ShangHai-At-Risk-for-Psychosis (SHARP) study: Associations with clinical outcomes.

OBJECTIVES: 1) to assess generalizability of neurocognitive deficits reported in previous Western clinical high-risk (CHR) for psychosis studies in a prodromal program in Shanghai, China; and 2) to investigate neurocognition in CHR subjects in relation to a broader range of clinical outcomes (e.g. remission) than presence or absence of psychosis. METHOD: Baseline neurocognitive assessments of CHR (n = 217) and healthy control (HC; n = 133) subjects were compared based on 1-year follow-up clinical status using MANOVA. CHR subjects were first divided into 'converter' (CHR-C; n = 41) and 'non-converter' (CHR-NC; n = 155) to psychosis groups and compared to HC and to each other. CHR subjects were then divided into 'remission' (i.e. achieved remission; n = 102), 'symptomatic' (persistent positive symptoms in the absence of conversion; n = 37) and 'poor-outcome' (converted and symptomatic subjects who did not respond to treatment; n = 57) groups. RESULTS: CHR neurocognitive performance was broadly impaired compared to HC; CHR-C subjects showed lower performance in processing speed and visual learning than CHR-NC. CHRs with poor clinical outcomes showed lower performance on most MCCB tasks compared to HC, particularly in learning and processing speed, as clinical outcome worsened from remission to symptomatic to poor outcome groups. CONCLUSIONS: Level and pattern of baseline neurocognitive weaknesses in SHARP CHR subjects were similar to those in NAPLS-2. Outcome stratification into remission, symptomatic and poor groups was associated with increasing cognitive deficits in learning and processing speed. These findings support cross-cultural generalizability and advance understanding of CHR neurocognitive heterogeneity associated with 1-year clinical outcomes.

Clinical Outcomes and Satisfaction following Neuropsychological Assessment for Adults: A Community Hospital Prospective Quasi-Experimental Study.

OBJECTIVE: Patients and other stakeholders generally report high satisfaction with neuropsychological evaluations (NPEs), but no research has examined effects of cognitive, emotional, and other factors that often prompt evaluations. A prospective, quasi-experimental study was conducted to examine self-reported cognitive and psychiatric symptoms, self-efficacy, motivation, and satisfaction following a NPE. METHOD: Participants from a neuropsychology clinic who were diagnosed with AD/HD and/or a DSM-IV mood disorder based on a NPE were included, and excluded if diagnosed with dementia or failure on performance validity tests. RESULTS: To examine whether a NPE with an interventional feedback session was associated with outcomes, changes from baseline to post-feedback session were examined with repeated-measures analysis of variance. Pearson correlations determined whether changes in hypothesized mechanisms (i.e., self-efficacy, goal importance and confidence ratings, and use of cognitive strategies) were related to changes in cognitive or psychiatric symptom severity. At follow-up, participants reported reductions in psychiatric (change in Brief Symptom Inventory depression: M = -2.8, SD = 4.4, range = -11 to 8, ${\eta}_p^2$=.30; anxiety: M = 3.2, SD = 6.6, range = -21 to 10, ${\eta}_p^2$ = .20) and cognitive symptoms (change in Multiple Ability Self-Report Questionnaire attention: M = -0.3, SD = 0.5, range = -1.6 to 0.5, ${\eta}_p^2$ = .31; verbal memory: M = -0.3, SD = 0.5, range = -1.1 to 0.5, ${\eta}_p^2$ = .24; language: M = -0.4, SD = 0.4, range = -1.3 to 0.4, ${\eta}_p^2$ = .48), and improved cognition (change in Meta-Memory Questionnaire ability: M = 4.4,SD = 6.2, range = -10 to 16, ${\eta}_p^2$ = .35; contentment: M = 4.3, SD = 4.5, range = -7 to 14, ${\eta}_p^2$ = .49). Participants reported increased self-efficacy for general and evaluation-specific goals. Increased goal-specific self-efficacy was associated with large reductions in psychiatric symptoms. CONCLUSIONS: Participants reported high levels of satisfaction with the NPE. Results support the clinical utility of NPE and feedback, and underscore the importance of individualized goal setting as part of the evaluation process.

Neurocognitive profiles in the prodrome to psychosis in NAPLS-1.

BACKGROUND: Most studies of neurocognitive functioning in Clinical High Risk (CHR) cohorts have examined group averages, likely concealing heterogeneous subgroups. We aimed to identify neurocognitive subgroups and to explore associated outcomes. METHODS: Data were acquired from 324 participants (mean age 18.4) in the first phase of the North American Prodrome Longitudinal Study (NAPLS-1), a multi-site consortium following individuals for up to 2 1/2 years. We applied Ward's method for hierarchical clustering data to 8 baseline neurocognitive measures, in 166 CHR individuals, 49 non-CHR youth with a family history of psychosis, and 109 healthy controls. We tested whether cluster membership was associated with conversion to psychosis, social and role functioning, and follow-up diagnosis. Analyses were repeated after data were clustered based on independently developed clinical decision rules. RESULTS: Four neurocognitive clusters were identified: Significantly Impaired (n = 33); Mildly Impaired (n = 82); Normal (n = 145) and High (n = 64). The Significantly Impaired subgroup demonstrated the largest deviations on processing speed and memory tasks and had a conversion rate of 58%, a 40% chance of developing a schizophrenia spectrum diagnosis (compared to 24.4% in the Mildly Impaired, and 10.3% in the other two groups combined), and significantly worse functioning at baseline and 12-months. Data clustered using clinical decision rules yielded similar results, pointing to high convergent validity. CONCLUSION: Neurocognitive profiles vary substantially in their severity and are associated with diagnostic and functional outcome, underscoring neurocognition as a predictor of illness outcomes. These findings, if replicated, are a first step toward personalized treatment for individuals at-risk for psychosis.

Development of a Boston Treatment Program for Youth at Clinical High Risk for Psychosis: Center for Early Detection, Assessment, and Response to Risk (CEDAR).

Over the past two decades, increasing attention has been given to the importance of early intervention for psychosis. This article describes the development of the Center for Early Detection, Assessment and Response to Risk (CEDAR), which focuses on early identification and treatment of youth at clinical high risk for psychosis. There are relatively few models in the United States for such programs, and we present our developmental story, focusing mainly on the CEDAR Clinic, as a case study of how such a program can develop. We describe the rationale, infrastructure, and services provided at the CEDAR Clinic, and present some descriptive data from the CEDAR Clinic through 2016. A case example is provided to illustrate treatment at CEDAR. We hope that the cultural history of our program's development is informative for clinicians and policy makers as one model of how to build an early intervention service. We believe that this article is timely in view of the growing momentum in the United States for developing programs for intervening as early as possible for youth at clinical high risk for psychosis.

Healthy adolescent performance on the MATRICS Consensus Cognitive Battery (MCCB): Developmental data from two samples of volunteers.

The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n=126) and Boston Center for Intervention Development and Applied Research (CIDAR; n=13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions.

Family-Directed Cognitive Adaptation Pilot: Teaching Cognitive Adaptation to Families of Individuals with Schizophrenia.

Cognitive deficits are a major determinant of functional outcome in schizophrenia. A promising treatment involves teaching individuals to use cognitive adaptation strategies to minimize the functional impact of cognitive difficulties. We developed Family Directed Cognitive Adaptation (FCA) to train caregivers to help their relatives with schizophrenia use cognitive adaptations to improve living skills. The goal of this open pilot trial was to examine the feasibility of FCA. Ten adults with schizophrenia, each with at least one relative, participated in FCA and were evaluated at baseline, post-treatment, and 6-month follow-up. Domains assessed included adaptive functioning, psychiatric symptoms, school/work involvement, hospitalizations, family burden, and treatment satisfaction. Participants reported high levels of satisfaction with FCA, and all families completed the 16-session intervention. Relatives reported reduced burden at termination and follow-up. No participants were hospitalized during the treatment or follow-up period, and rates of work/school involvement increased from 30% at baseline to 50% at the end of treatment and follow-up. Individuals improved in negative symptoms and adaptive functioning over the course of treatment, but these gains were not maintained. This pilot provides preliminary support for the acceptability and feasibility of FCA, and points to the need to address the maintenance of treatment gains after termination.

Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth.

BACKGROUND: Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. METHODS: This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at "clinical high risk" (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13-17), or adulthood (18+). RESULTS: Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. CONCLUSION: Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories.

The nature and evolution of insight in schizophrenia: a multi-informant longitudinal study of first-episode versus chronic patients.

BACKGROUND AND AIMS: This study investigated a novel distinction between two possible sources of poor insight in schizophrenia: primary unawareness, in which the ill person is not aware that other people think one has a problem, and secondary unawareness (or disagreement), in which a person does appreciate that other people think one has a problem. A secondary goal was to compare the evolution of insight in first-episode and chronic schizophrenia. METHODS: Sixty-eight first-episode and 51 chronic patients were administered two versions of the Scale of Unawareness of Mental Disorder (SUMD) at three time points: hospital admission, discharge, and 6-month post-discharge. In the first standard SUMD version, they were asked about their own opinions, whereas in the second modified version, they were asked about their best guess of their doctor's opinion. RESULTS: While overall level of unawareness remained stable within each single episode, there were significant Type of Unawareness (primary versus secondary) by Clinical Status (admission versus discharge versus 6-month post-discharge) and Type of Unawareness by Phase of Illness (first-episode versus chronic) interaction effects. More specifically, in the first-episode group, primary unawareness steadily decreased over time. In contrast, in the chronic group, primary unawareness decreased markedly during hospitalization and returned to baseline after discharge. CONCLUSIONS: These results provide preliminary support for the notion that impaired insight is an additive outcome of primary unawareness and disagreement, and that change in insight over time occurs mostly at the level of their relative proportion as opposed to their overall sum. Implications for studying and treating poor insight in schizophrenia are discussed.

Development of liability syndromes for schizophrenia: where did they come from and where are they going?

Three decades after Paul Meehl proposed the term "schizotaxia" to describe a conceptual framework for understanding the liability to schizophrenia, Ming Tsuang et al. at Harvard University reformulated the concept as a clinical syndrome with provisional research criteria. The reformulated view relied heavily on more recent data showing that many non-psychotic, un-medicated biological relatives of individuals with schizophrenia showed difficulties in cognitive and other clinical functions that resembled those seen in their ill relatives. The reformulation raised questions about both whether and when liability could be assessed validly in the absence of psychosis, and about the extent to which symptoms of liability are reversible. Both questions bear on the larger issue of early intervention in schizophrenia. This article reviews the efforts of Tsuang et al. to conceptualize and validate schizotaxia as one such syndrome of liability. Towards this end, liability is considered first more generally as an outcome of interactive genetic and environmental factors. Liability is then considered in the context of endophenotypes as a concept that is both broader and is potentially more specific (and predictive) than many DSM or ICD diagnostic symptoms. Liability syndromes are then considered in the context of their proximity to illness, first by reviewing prodromal syndromes (which are more proximal), and then by considering schizotaxia, which, as it is currently formulated, is pre-prodromal and, therefore, less proximal. Finally, challenges to validation and future directions for research are considered.

Change in neuropsychological functioning over one year in youth at clinical high risk for psychosis.

Schizophrenia and related psychotic disorders are associated with significant neuropsychological (NP) impairments. Yet the onset and developmental evolution of these impairments remains incompletely characterized. This study examined NP functioning over one year in a sample of youth at clinical high risk (CHR) for psychosis participating in a treatment study. We assessed functioning across six cognitive domains at two time points in a sample of 53 CHR and 32 healthy comparison (HC) subjects. Linear regression of HC one-year scores was used to predict one-year performance for CHR from baseline scores and relevant demographic variables. We used raw scores and MANOVAs of the standardized residuals to test for progressive impairment over time. NP functioning of CHR at one year fell significantly below predicted levels. Effects were largest and most consistent for a failure of normative improvement on tests of executive function. CHR who reached the highest positive symptom rating (6, severe and psychotic) on the Structured Interview of Prodromal Syndromes after the baseline assessment (n = 10/53) demonstrated a particularly large (d = -1.89), although non-significant, discrepancy between observed and predicted one-year verbal memory test performance. Findings suggest that, although much of the cognitive impairment associated with psychosis is present prior to the full expression of the psychotic syndrome, some progressive NP impairments may accompany risk for psychosis and be greatest for those who develop psychotic level symptoms.

Neurocognitive and clinical dysfunction in adult Chinese, nonpsychotic relatives of patients with schizophrenia: Findings from the Changsha study and evidence for schizotaxia.

Many first-degree relatives of patients with schizophrenia demonstrate deficits in neurocognitive, social, clinical and other dimensions, in the absence of psychosis. Based on a reformulation of Meehl's concept of "schizotaxia" as a clinically meaningful syndrome reflecting liability to schizophrenia, we proposed research criteria in relatives focused on negative symptoms and neurocognitive deficits. Here we assess validity of the syndrome in a sample of Chinese adult relatives by assessing measures of concurrent validity, and by using cluster analysis to test the hypothesis that relatives could be grouped into distinct schizotaxic and non-schizotaxic subgroups based on our diagnostic criteria. Thirty community comparison subjects (CCS) and 189 relatives were evaluated with measures of clinical, cognitive, medical and social function at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan, China), as part of a larger study to identify and ameliorate symptoms of schizotaxia. Using modified research criteria based on negative symptoms and neurocognitive deficits, 103 relatives did not meet criteria for schizotaxia, and 86 did. The cluster analysis confirmed a two-group solution that corresponded to our non-schizotaxic and schizotaxic groups, but it increased the non-schizotaxic group to 135, and reduced the schizotaxic group to 53. Both schizotaxic groups, but especially the cluster-derived group, showed significant impairment in a variety of independent (i.e. non-criterion related) measures of clinical and social function. These findings provide additional validity for a liability syndrome, and for its utility as an intervention target for strategies aimed at ameliorating both its core and its associated symptoms.

Auditory working memory impairments in individuals at familial high risk for schizophrenia.

OBJECTIVES: The search for predictors of schizophrenia has accelerated with a growing focus on early intervention and prevention of psychotic illness. Studying nonpsychotic relatives of individuals with schizophrenia enables identification of markers of vulnerability for the illness independent of confounds associated with psychosis. The goal of these studies was to develop new auditory continuous performance tests (ACPTs) and evaluate their effects in individuals with schizophrenia and their relatives. METHODS: We carried out two studies of auditory vigilance with tasks involving working memory (WM) and interference control with increasing levels of cognitive load to discern the information-processing vulnerabilities in a sample of schizophrenia patients, and two samples of nonpsychotic relatives of individuals with schizophrenia and controls. Study 1 assessed adults (mean age = 41), and Study 2 assessed teenagers and young adults age 13-25 (M = 19). RESULTS: Patients with schizophrenia were impaired on all five versions of the ACPTs, whereas relatives were impaired only on WM tasks, particularly the two interference tasks that maximize cognitive load. Across all groups, the interference tasks were more difficult to perform than the other tasks. Schizophrenia patients performed worse than relatives, who performed worse than controls. For patients, the effect sizes were large (Cohen's d = 1.5), whereas for relatives they were moderate (d = ~0.40-0.50). There was no age by group interaction in the relatives-control comparison except for participants <31 years of age. CONCLUSIONS: Novel WM tasks that manipulate cognitive load and interference control index an important component of the vulnerability to schizophrenia.

Are neurocognitive, clinical and social dysfunctions in schizotaxia reversible pharmacologically?: Results from the Changsha study.

The Changsha study identifies adult, non-psychotic relatives of patients with schizophrenia who show deficits in neurocognitive, social, clinical and other dimensions, and who meet provisional criteria for a liability syndrome for schizophrenia ('schizotaxia'). In this study, we investigated whether negative symptoms, neurocognitive deficits, or other measures of clinical and social function in subjects who met our research criteria for schizotaxia were amenable to pharmacological remediation with a low dose (2.0 mg) of risperidone, a second generation antipsychotic medication. One hundred eighty nine relatives were assessed at the Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha (Hunan Province, China), between 12/06 - 12/08. Eighty six of these individuals met modified criteria for schizotaxia, and 36 agreed to enter a 6-week, double-blind, placebo-controlled protocol. ANCOVAs using age and gender as covariates showed significant improvement in the risperidone group (n=20) on neurocognitive function (Wisconsin Card Sorting Test Total Errors and Perseverative Errors) and on a self-report measure of social function (Social Adjustment Scale), compared to the placebo-control group (n=16). Effect sizes were small to medium. Notably, risperidone effect sizes were larger (medium to large) in a subset of subjects (risperidone=15; placebo=10) whose membership in the schizotaxic group was supported empirically by cluster analysis. Negative symptoms did not change significantly in either analysis. The results are generally consistent with previous open-label investigations of risperidone administration in subjects with schizotaxia, and provide evidence that some neurocognitive and clinical problems are amenable to remediation in non-psychotic relatives of people with schizophrenia.