Overlap between individual differences in cognition and symptoms of schizophrenia.

BACKGROUND: Neurocognitive impairment is a core feature of schizophrenia spectrum disorders (SSDs), and the relationship between cognition and symptoms in SSDs has been widely researched. Negative symptoms are related to a wide range of cognitive impairments; however, the aspects of negative symptoms that underpin this relationship have yet to be specified. STUDY DESIGN: We used iterative Constrained Principal Component Analysis (iCPCA) to explore the relationship between 18 cognitive measures (including processing speed, attention, working, spatial and verbal memory and executive functions) and 46 symptoms in schizophrenia at the individual item level while minimizing the risk of Type I errors. ICPCA was conducted on a sample of SSD patients in the early stages of psychiatric treatment (n = 121) to determine the components of cognition overlapping with symptoms measured by the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: We found that a verbal memory component was associated with items from SANS and SAPS related to impoverished and disorganized emotional communication, language, and thought. In contrast, a working memory component was associated with SANS items related to motor system impoverishment. CONCLUSIONS: The iCPCA allowed us to explore the associations between individual items, optimized to understand the overlap between symptoms and cognition. The specific symptoms linked to verbal and working memory impairments imply distinct brain networks, which further investigation may lead to our deeper understanding of the illness and the development of treatment methods.

Cortical impoverishment in a stable subgroup of schizophrenia: Validation across various stages of psychosis.

BACKGROUND: Cortical thinning is a well-known feature in schizophrenia. The considerable variation in the spatial distribution of thickness changes has been used to parse heterogeneity. A 'cortical impoverishment' subgroup with a generalized reduction in thickness has been reported. However, it is unclear if this subgroup is recoverable irrespective of illness stage, and if it relates to the glutamate hypothesis of schizophrenia. METHODS: We applied hierarchical cluster analysis to cortical thickness data from magnetic resonance imaging scans of three datasets in different stages of psychosis (n = 288; 160 patients; 128 healthy controls) and studied the cognitive and symptom profiles of the observed subgroups. In one of the samples, we also studied the subgroup differences in 7-Tesla magnetic resonance spectroscopy glutamate concentration in the dorsal anterior cingulate cortex. RESULTS: Our consensus-based clustering procedure consistently produced 2 subgroups of participants. Patients accounted for 75%-100% of participants in one subgroup that was characterized by significantly lower cortical thickness. Both subgroups were equally symptomatic in clinically unstable stages, but cortical impoverishment indicated a higher symptom burden in a clinically stable sample and higher glutamate levels in the first-episode sample. There were no subgroup differences in cognitive and functional outcome profiles or antipsychotic exposure across all stages. CONCLUSIONS: Cortical thinning does not vary with functioning or cognitive impairment, but it is more prevalent among patients, especially those with glutamate excess in early stages and higher residual symptom burden at later stages, providing an important mechanistic clue to one of the several possible pathways to the illness.

Normal-range verbal memory in the first-episode of psychosis: Clinical and functional outcomes across 24 months and impact of estimated verbal memory decrement.

Verbal memory (VM) dysfunction is prevalent in first-episode psychosis (FEP) and has major impacts on long-term functional and clinical outcomes. Nevertheless, a substantial proportion of FEP patients have VM performance in the norm, called normal-range (NR) VM, and only a few studies have explored its relation to outcomes. Moreover, probable decrements between estimated premorbid and current cognitive performance could confuse the relationship between VM and clinical or functional outcomes in FEP patients. These potential interactions have not yet been considered in FEP, thus, we examined 1) the longitudinal relationship between VM performance (NR vs. below NR (BNR)) in FEP and clinical and functional outcomes over 24 months following admission to treatment, and 2) compared the clinical and functional status of NR patients with and without cognitive decrement at baseline and 12 months. A total of 271 patients (BNR = 114, NR = 157; 81 out of 105 NR with decrement) completed measures of psychosocial functioning and clinical symptoms at baseline, month 12, and month 24. Generalized Estimating Equations and unpaired t-tests were used to address the first and second aim, respectively. NR demonstrated better functioning and fewer negative symptoms when compared to BNR. Interestingly, NR patients with decrement reported significantly more negative symptoms at baseline compared to their counterparts without decrement. These findings document that a large proportion (57.9 %) of FEP patients have NR VM that appear to be functionally advantageous but that NR VM is nuanced by the presence or absence of a potential decrement early in the developmental course of the disorder.

An ecologically sensitive measure of executive cognition (the Breakfast Task) improves prediction of functional outcome in schizophrenia.

Previous work has found that the Breakfast Task (BT), a computerized, ecologically informed executive ability measure, is sensitive to group differences in aging, acquired brain injury, and Parkinson's disease. We investigated whether this measure improves the prediction of functional status over and above standard measures of general intellectual ability, relationship perception, life skills, and symptom severity in individuals with schizophrenia. Regression analyses were conducted to evaluate the joint and incremental validity of the BT in predicting functional disability scores on the World Health Organization Disability Assessment Scale (WHODAS 2.0). Analyses with combined patient (n = 25) and control (n = 32) participants showed that participant status (patients versus control) was the only significant predictor of functional outcome. However, in the patient data, the proportion of variance accounted for improved significantly (model R2 of 4% vs. 25%) when BT scores were added to a model containing clinical (Brief Psychiatric Rating Scale), social (Relationships Across Domains), intellectual (Wechsler Abbreviated Scale of Intelligence), and life skills (Canadian Objective Assessment of Life Skills) measures. Results suggest that the BT, a tool that captures complex executive functioning, improves the prediction of disability in patients with schizophrenia and has potential assessment applications.

Cognitive decline and impairment in schizophrenia spectrum disorders reconsidered.

BACKGROUND: This study applied an algorithm developed to identify schizophrenia spectrum disorder patients with probable decrements between estimated premorbid and current cognitive ability (Keefe et al., 2005). Cognitive trajectories and associated functional status were examined in patients and control participants. METHODS: Patients with schizophrenia or schizoaffective disorder (n = 139) and control participants (n = 63) completed measures of verbal and working memory, processing speed, verbal fluency, reading ability and non-verbal reasoning. A predicted cognitive composite score was generated using control participants' parental education and reading scores, consistent with methods in Keefe et al. (2005), and compared to current performance. Three performance trajectory profiles were identified: decrement, stable, and increment. Functionality and clinical status were assessed with the Multidimensional Scale of Independent Functioning (MSIF) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: Approximately 60% (n = 83) of patients demonstrated a decrement trajectory, 16% (n = 22) demonstrated an increment trajectory, and 24% (n = 34) demonstrated a stable trajectory. Patients with decrement profiles were significantly more symptomatic (negative) and functionally impaired (MSIF) than those with increment profiles. Patients with increment and normal-range performance profiles remained functionally deficient relative to controls. CONCLUSIONS: Schizophrenia and schizoaffective patients meeting psychometric criteria for cognitive decline relative to estimated premorbid levels are common in the outpatient population but may occur less frequently than earlier estimates suggest. Minorities with stable and improved performance profiles also exist, show clinical and functional advantage relative to more typical patients, but underperform healthy controls.

The duality of human cognition: operations and intentionality in mental life and illness.

What people think about, the intentional aspect of cognition, is distinguished from its operational aspect, or how proficiently they think. Many psychiatric disorders as well as social problems like racism, are defined largely by specified thought contents, whereas neurological disorders including dementia are defined by low proficiency. Intentionality contrasts with operational cognition in resisting objectification and in being expressed primarily in verbal narratives and subjective self-disclosure. This yields insecure data that have slowed progress in fields where intentional cognition plays a key role. The question is how to produce more secure knowledge and open the intentional domain itself to objective investigation. The use of operational methods to infer intentionality has provided only partial answers. However, the science of reconstructing mental events with neural data is providing a new horizon for the study of intentional cognition. Reconstruction science must address major challenges related to fidelity and validity. Nevertheless, this approach is showing the first steps on the road to accessing and revealing objectively the contents of thought.

Cortical thickness correlates of cognitive performance in cognitively-matched individuals with and without schizophrenia.

Schizophrenia is characterized by psychosis and, in most cases, cognitive impairment. It is unclear, however, whether these elements of the disorder represent distinct or related disease processes. Accordingly, this study investigated 3-way interactions between group, cognition and cortical thickness in cognitively-matched patients with schizophrenia and healthy control groups. Patients and healthy controls were group-matched on demographics and a broadly-based index of cognitive performance. T1-weighted images were processed using Freesurfer. Variable selection techniques were applied to determine which regions best predicted 3-way interaction effects. Independent variables included age, sex, IQ, and 87 regional cortical thickness values strongly associated with group or cognition. Antipsychotic treatment effects were also investigated. Twenty regions were selected by the best fitting model. The top 6 regions included the left pre- and post-central, left superior frontal and temporal and right rostral and caudal middle frontal cortices. No antipsychotic treatment effects were seen. Cortical thinning in schizophrenia exists even in the absence of cognitive impairment. Our findings support the separation of psychosis and cognitive impairment as independent disease processes, with distinct relations with cortical thickness in prefrontal cortical areas. Parsing out these two disease processes will increase understanding of heterogeneity in schizophrenia and may modify treatment targets.

The continuing story of schizophrenia and schizoaffective disorder: One condition or two?

Although schizophrenia and schizoaffective disorder remain separable in diagnostic systems, the validity of the distinction is uncertain. This study asked whether schizophrenia and schizoaffective disorder are distinguishable on selected cognitive, social cognitive and structural social brain measures. Outpatients with a diagnosis of schizophrenia (n = 44) or schizoaffective disorder (n = 29) and non-psychiatric control participants (n = 62) were studied. Patients were assessed clinically (Positive and Negative Syndrome Scale) and all participants were administered a battery of cognitive (MATRICS Consensus Cognitive Battery; Wechsler Abbreviated Scale of Intelligence, Wide Range Achievement Reading) and social cognitive (Reading the Mind in the Eyes, Mayer-Salovey-Caruso Emotional Intelligence Test; MSCEIT) tasks. In addition, participants underwent structural magnetic resonance imaging (MRI) to yield cortical thickness data for 42 regions associated with the social brain network. Results showed no significant differences between patient groups on 17/18 cognitive/social cognitive and social brain cortical thickness measures. In contrast, schizophrenia and schizoaffective disorder patients differed from controls on 16/18 and 11/18 measures respectively. Schizoaffective disorder patients outperformed schizophrenia patients on an emotion regulation task (MSCEIT). Schizophrenia and schizoaffective disorder are largely indistinguishable on key cognitive, social cognitive and neural measures. The continuing separation of these syndromes in diagnostic systems and disease models requires is questionable and requires further attention.

Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia.

This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ±â€Š10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

Normal-range verbal-declarative memory in schizophrenia.

OBJECTIVE: Cognitive impairment is prevalent and related to functional outcome in schizophrenia, but a significant minority of the patient population overlaps with healthy controls on many performance measures, including declarative-verbal-memory tasks. In this study, we assessed the validity, clinical, and functional implications of normal-range (NR), verbal-declarative memory in schizophrenia. METHOD: Performance normality was defined using normative data for 8 basic California Verbal Learning Test (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) recall and recognition trials. Schizophrenia patients (n = 155) and healthy control participants (n = 74) were assessed for performance normality, defined as scores within 1 SD of the normative mean on all 8 trials, and assigned to normal- and below-NR memory groups. RESULTS: NR schizophrenia patients (n = 26) and control participants (n = 51) did not differ in general verbal ability, on a reading-based estimate of premorbid ability, across all 8 CVLT-II-score comparisons or in terms of intrusion and false-positive errors and auditory working memory. NR memory patients did not differ from memory-impaired patients (n = 129) in symptom severity, and both patient groups were significantly and similarly disabled in terms of functional status in the community. CONCLUSION: These results confirm a subpopulation of schizophrenia patients with normal, verbal-declarative-memory performance and no evidence of decline from higher premorbid ability levels. However, NR patients did not experience less severe psychopathology, nor did they show advantage in community adjustment relative to impaired patients. (PsycINFO Database Record

Neurocognitive normality in schizophrenia revisited.

The validity and significance of normal range neurocognition in schizophrenia remain unclear and controversial. We assessed whether normal range patients and controls demonstrate evidence of decline relative to premorbid ability and differ in performance profiles across measures, including those external to the normality criterion. In addition, we compared below normal range healthy control participants with patients at the same ability level. Performance normality was defined as a MATRICS Consensus Cognitive Battery (MCCB) composite T score between 40 and 60. Patients (n = 17) and controls (n = 24) meeting the criterion were compared on MCCB domain scores and on independent measures of reading ability, probabilistic and social reasoning. Patients (n = 19) and controls (n = 20) scoring below 40 on the MCCB composite were compared on the same set of measures. Cognitively normal range patients and controls did not differ on estimated premorbid ability or decline and differed only on the Processing Speed domain of the MCCB. Performance did not differ across other domains or on social and probabilistic reasoning tasks. Cognitively below normal range patients and controls showed marked discrepancies between premorbid and current ability, but there were no group differences. In addition, below normal range groups did not differ on any MCCB domain score or in terms of external cognitive measures. Cognitively normal range schizophrenia patients may be largely indistinguishable from normal range controls, with the exception of processing speed performance. More typical schizophrenia patients below the normal range may be indistinguishable from low-performing controls even in terms of processing speed.

Community outcome in cognitively normal schizophrenia patients.

Recent reports suggest that cognition is relatively preserved in some schizophrenia patients. However, little is known about the functional advantage these patients may demonstrate. The purpose of this study was to identify cognitively normal patients with a recently developed test battery and to determine the functional benefit of this normality relative to cognitively impaired patients. Average-range cognitive ability was defined by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) composite score (T≥40) and applied to 100 patients with schizophrenia or schizoaffective disorder and to 81 non-psychiatric research participants. With group assignment adjusted for demographic variables, this procedure yielded 14 cognitively normal patients, 21 cognitively impaired patients, and 21 healthy adults with normal-range MCCB scores. Cognitively normal patients were indistinguishable from controls across all MCCB scales. Furthermore, their performance was superior to impaired patients on all scales except Social Cognition. Cognitively normal patients were also superior to impaired patients on a summary index of simulated life skills and functional competence. Nevertheless, both patient groups were equally disadvantaged relative to controls in independent community living. These findings suggest that normal-range cognition exists in schizophrenia, but fails to translate into enhanced community outcome.

Preserved, deteriorated, and premorbidly impaired patterns of intellectual ability in schizophrenia.

OBJECTIVE: The main purpose of this investigation was to identify patterns of intellectual performance in schizophrenia patients suggesting preserved, deteriorated, and premorbidly impaired ability, and to determine clinical, cognitive, and functional correlates of these patterns. METHOD: We assessed 101 patients with schizophrenia or schizoaffective disorder and 80 non-psychiatric control participants. The "preserved" performance pattern was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference <10 points). The "deteriorated" pattern was defined by a difference between estimated premorbid and current IQ estimates of 10 points or more. The premorbidly "impaired" pattern was defined by below average estimated premorbid and current IQ and no evidence of decline greater than 10 points. Preserved and deteriorated patterns in healthy controls were also identified and studied in comparison to patient findings. The groups were compared on demographic, neurocognitive, clinical and functionality variables. RESULTS: Patients with the preserved pattern outperformed those meeting criteria for deteriorated and compromised intellectual ability on a composite measure of neurocognitive ability as well as in terms of functional competence. Patients demonstrating the deteriorated and compromised patterns were equivalent across all measures. However, "preserved" patients failed to show any advantage in terms of community functioning and demonstrated cognitive impairments relative to control participants. CONCLUSIONS: Our results suggest that proposed patterns of intellectual decline and stability exist in both the schizophrenia and general populations, but may not hold true across other cognitive abilities and do not translate into differential functional outcome.

Stability and change in symptoms, cognition, and community outcome in schizophrenia.

It has been well established that neurocognitive deficits are a core feature in schizophrenia and predict difficulties in functional independence. However, few studies have assessed the longitudinal stability of cognition and key aspects of functional outcome concurrently. Even less attention has been directed at the contingency of cognitive change on real world outcome changes. Accordingly, this study will assess the extent to which significant changes in cognition and community status are independent or related. As a point of comparison, the stability of clinical symptom status and the relationship between symptom and outcome change are evaluated. Symptoms, cognitive abilities, and community outcome was assessed in 128 patients with schizophrenia at baseline and again one year later. Intraclass correlation coefficients were used to index stability and reliable change index analyses quantified the prevalence of significant improvement or deterioration in each of the three illness features. Results from these analyses revealed that symptom status, cognitive functioning, and community outcome are similarly stable in treated schizophrenia outpatients. A small proportion of the sample demonstrated significant improvement or deterioration in these domains, with only weak evidence that such change was predicted by changes in symptoms or cognition. Further, there was no strong evidence of a preferential relationship for cognition relative to symptoms in relation to functional outcome. These results shed light on the strength and nature of the cognition-real world outcome relationship in schizophrenia and have implications for pharmacological and behavioral interventions aimed at improving real world outcome.

WAIS-IV profile of cognition in schizophrenia.

The Wechsler Adult Intelligence Scale (WAIS) has been used extensively to study impairment across a range of cognitive domains in schizophrenia. However, cognitive performance among those with the illness has yet to be examined using the newest edition of this measure. Hence, the current study aims first, to provide WAIS-IV normative data for Canadian individuals with schizophrenia of low average intelligence; second, to examine schizophrenia performance on all WAIS-IV subtest, index and general intelligence scores relative to healthy comparison subjects; and third, to revalidate the pattern of impairment identified in this clinical group using the WAIS-III, where processing speed (PS) was most affected, followed by working memory (WM), perceptual reasoning (PR) and verbal comprehension (VC). The WAIS-IV was administered to outpatients with schizophrenia and their performance compared with age, gender, and education matched controls. WAIS-IV schizophrenia performance data are provided. Analyses revealed significant impairment on several tasks, including the new Cancellation subtest and the VC supplemental subtest, Comprehension. At the index score level, group differences in PS were significantly larger than those observed in all other cognitive domains. Impairments were also observed in WM amid relatively preserved performance in VC, thereby confirming the pattern of impairment identified using the WAIS-III.

The Canadian Objective Assessment of Life Skills (COALS): a new measure of functional competence in schizophrenia.

This study examined the reliability and validity of a new performance-based measure of functional competence for individuals with serious mental illness, the Canadian Objective Assessment of Life Skills (COALS). The COALS assesses both routinized procedural knowledge routines (PKR) and executive operations (EXO) in order to capture functional outcome variance. The COALS was administered to 101 outpatients with schizophrenia and schizoaffective disorder and 80 non-psychiatric controls. One month later, 95 patients and 63 controls completed a follow-up assessment. Measures of psychopathology, neurocognition, functionality and community adjustment were also administered. Results indicated that the COALS summary scores had good test-retest reliability for patient data. Further, the COALS correlated with other measures of functionality and with negative symptoms, but was independent of positive symptoms, demonstrating concurrent and discriminant validity. The overall COALS summary score added incremental validity to the prediction of community independence over and above the contribution of symptoms, intellectual ability and neurocognitive performance. Inclusion of EXO scores provided incremental validity not available with PKR scores alone. The COALS increases the number of functional competence instruments and offers the advantage of specific validity while incorporating important distinctions in cognitive performance.

Exploring logical reasoning abilities in schizophrenia patients.

OBJECTIVE: To assess deductive reasoning in schizophrenia patients with special reference to whether accuracy varies across type of stimulus problem. Previous research suggests that patients, unlike healthy controls, are insensitive to emotionally provocative (salient) problem content. METHOD: A syllogistic reasoning task consisting of five argument types varying in salience, congruence with commonly held beliefs and meaningfulness was administered along with standard intellectual and symptom measures to 25 schizophrenia patients and 26 healthy control participants. RESULTS: Patients performed below control participants in all reasoning task conditions, but group differences were non significant after controlling for IQ. There were no significant interactions between group and argument type in terms of reasoning accuracy and both patients and controls performed better when reasoning with belief congruent material. In addition, no relation between deduction and paranoid symptoms was found. CONCLUSION: Formal deductive reasoning abnormalities in schizophrenia are a reflection of the broadly based cognitive impairment documented in the illness.

"Real world" functioning in schizophrenia patients and healthy adults: assessing validity of the Multidimensional Scale of Independent Functioning.

As treatment efforts to enhance cognitive abilities in schizophrenia increase, so too does the need for a critical appraisal of instruments that measure functionality and adjustment to community living. The Multidimensional Scale of Independent Functioning (MSIF; Jaeger et al., 2003) is a promising instrument that assesses functionality in relation to different life settings, performance levels, responsibilities and environmental supports. However, its applicability to the schizophrenia population has been questioned because relevant data are scarce. This study provides descriptive and validity-related information by reporting MSIF scores in healthy community-dwelling adults (n=71) and in schizophrenia outpatients (n=156). Results show that healthy adults performed within defined "normal" ranges in most MSIF domains in comparison to schizophrenia patients who showed moderate to severe impairments. Moreover, the MSIF distinguished between the two groups with accuracy rates as high as 98% and effect sizes (standardized mean group difference) above 2.0 in almost all domains. Accordingly, the MSIF is a potentially valuable measure of community independence that can inform treatment initiatives and may be adaptable to the evaluation of functionality changes over time. The unique structure and content of information obtained by the MSIF makes it a candidate for inclusion in studies aimed at developing a new generation of instruments for the assessment of real world functioning in schizophrenia.

An investigation of 3 neurocognitive subtypes in schizophrenia.

The purpose of this investigation was to identify patients with cognitively impaired, cognitively normal and verbal memory-impaired subtypes of schizophrenia and to examine their clinical and functional validity as distinct forms of the disorder. These subtypes occurred in 73 of 154 patients meeting DSM-IV criteria for schizophrenia or schizoaffective disorder. A control group comprised of 18 healthy participants was also analyzed. Patient subtype and healthy groups were compared on adjunct cognitive as well as clinical and functional measures. The data support the cognitive validity and differentiation of these subtypes, with evidence that the generalized cognitive normality/impairment distinction associates with important aspects of symptom severity and functional outcome. Support for the clinical and functional validity of the verbal memory subtype was more equivocal. Overall, cognitively-based subtyping merits additional attention in efforts to organize the heterogeneity of the schizophrenia syndrome.

Neurological soft signs in non-psychotic first-degree relatives of patients with schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Neurological soft signs (NSS) have been associated with the neuropsychopathology of schizophrenia, and have been proposed as candidate endophenotypes for this clinical group. However, the prevalence rate of NSS in non-psychotic first-degree relatives is not fully known. The authors systematically and quantitatively reviewed the literature to determine the magnitude of difference between: (1) first-degree non-psychotic relatives of schizophrenia patients and healthy controls, and (2) between schizophrenia patients and their non-psychotic relatives. METHODS: An article search and meta-analysis was conducted using the Comprehensive Meta-Analysis software package to quantify group differences. Mean effect sizes (standardized group mean differences) and associated confidence intervals along with homogeneity and publication bias tests and statistics were calculated. RESULTS: Search procedures identified 11 independent studies that met the inclusion criteria. Quantification of NSS differences yielded a mean effect size of 0.81 for schizophrenia patients and their non-psychotic relatives and 0.97 for non-psychotic relatives of schizophrenia patients and healthy controls. CONCLUSIONS: The current findings show that there are large group differences in NSS prevalence between patients with schizophrenia, non-psychotic relatives, and healthy controls. These results are consistent with the argument that NSS are familial in nature, segregate with the illness and may be valid and useful endophenotypes.