Biological, life course, and cross-cultural studies all point toward the value of dimensional and developmental ratings in the classification of psychosis

The diagnostic criteria for schizophrenia in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV¹) are based on the premise that it is a discrete illness entity, in particular, distinct from the affective psychoses. This assumption has persisted for more than a century, even though patients with a diagnosis of schizophrenia show a wide diversity of symptoms and outcomes, and no biological or psychological feature has been found to be pathognomonic of the disorder. However, there has been sustained, and indeed growing, criticism of the concept. For example, writing about the diagnosis of schizophrenia more than a decade ago,² one of Britain''s most sophisticated nosological experts, Ian Brockington, enjoined “It is important to loosen the grip which the concept of ‘schizophrenia’ has on the minds of psychiatrists. Schizophrenia is an idea whose very essence is equivocal, a nosological category without natural boundaries, a barren hypothesis. Such a blurred concept is ‘not a valid object of scientific enquiry’.”³ Should Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-V), persist with the neo-Kraepelinian concept of schizophrenia with all its defects, or should it deconstruct psychosis into its component dimensions? In this article, we will address the question by considering 2 main themes, firstly, the role of culture and ethnicity in the diagnosis of psychosis, and secondly, a life course approach to understanding psychosis. We will then discuss whether more progress would be achieved in DSM-V by abandoning the familiar categorical system and instead moving to a dimensional system which rates both developmental impairment and symptom factor scores. However, we will begin by briefly reviewing the recent history of the classification of the psychoses.     

Cognitive Impairment in Affective Psychoses: A Meta-analysis

It has recently been suggested that cognitive impairment should be included in the diagnostic criteria of schizophrenia. One of the main arguments in support of this suggestion has been the hope that cognitive impairment can help distinguish schizophrenia from bipolar disorder (BD). However, recent evidence shows that cognitive deficits occur in BD and persist beyond euthymia. Further, mood disorders with psychotic features might be expected to manifest greater cognitive impairment, which further complicates the potential to differentiate these disorders. The goal of the current meta-analysis was to examine the magnitude and characteristics of cognitive impairments in affective psychoses (AP). A systematic search of the existing literature sourced 27 studies that met the inclusion criteria. These studies compared cognitive performances of 763 patients with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls. Meta-regression and subgroup analyses were used to examine the effects of moderator variables. Meta-analyses of these studies showed that patients with AP were impaired in all 15 cognitive tasks with large effect sizes for most measures. There were no significant differences between the magnitude of impairments between the BD and major depressive disorder groups. The largest effect size was found for symbol coding, stroop task, verbal learning, and category fluency, reflecting impairments in elementary and complex aspects of attentional processing, as well as learning and memory. In general, the pattern of cognitive impairments in AP was similar to reported findings in euthymic patients with BD, but relatively more pronounced.     

Differences in cognitive impairment between schizophrenia and bipolar disorder: Considering the role of heterogeneity

Schizophrenia is associated with significant cognitive impairment. Bipolar disorder (BD) also presents with cognitive deficits that are similar to, albeit less severe, than those reported in schizophrenia. There has been controversy over whether selective deficits in social cognition or developmental trajectory of cognitive deficits can distinguish schizophrenia from BD. Also, available studies have not generally considered the potential effect of cognitive heterogeneity within the two disorders on between‐group differences. The current review examines the evidence on the specificity of social cognitive deficits and early neurocognitive impairment to schizophrenia and explores the overall outcome of studies investigating within and cross‐diagnosis cognitive heterogeneity in schizophrenia and BD. Current evidence does not support the specificity of social cognitive impairment to schizophrenia. Available studies also suggest that cognitive impairment in premorbid and early stages is evident not only in schizophrenia but also in many BD patients. Both schizophrenia and BD have a number of cognitive subgroups, including severe impairment, good functioning, and one or more selective or modest impairment clusters. While both disorders are represented in each cognitive subgroup, there are significant cross‐diagnostic differences regarding prevalences of individuals belonging to the severe impairment and good functioning subgroups. Individuals with schizophrenia are much more likely to exhibit severe cognitive impairment than individuals with BD and good cognitive functioning is more often observed in BD patients than schizophrenia patients. Further identification of the neurobiological and genetic characteristics of the cognitive subgroups in major psychoses can improve the validity of diagnostic systems and can advance the development of personalized management approaches, including cognitive remediation.     

Toxoplasma Gondii and Cognitive Deficits in Schizophrenia: An Animal Model Perspective

Cognitive deficits are a core feature of schizophrenia. Epidemiological evidence indicates that microbial pathogens may contribute to cognitive impairment in patients with schizophrenia. Exposure to Toxoplasma gondii (T. gondii) has been associated with cognitive deficits in humans. However, the mechanisms whereby the parasite impacts cognition remain poorly understood. Animal models of T. gondii infection may aid in elucidating the underpinnings of cognitive dysfunction. Here, we (1) overview the literature on the association of T. gondii infection and cognitive impairment, (2) critically analyze current rodent models of cognitive deficits resulting from T. gondii infection, and (3) explore possible mechanisms whereby the parasite may affect cognitive function.Key words: infection, immune system, kynurenine, learning and memory, gene–, environment interactions, Toxoplasma     

Should cognitive deficit be a diagnostic criterion for schizophrenia?

This review examines the question of whether cognitive deficits in schizophrenia are sufficiently reliable, stable and specific to warrant inclusion in the diagnostic criteria for schizophrenia. The literature provides evidence that cognitive deficits are highly prevalent and fairly marked in adult patients with schizophrenia. Similar deficits have been found in children and adolescents with schizophrenia, and in children before they exhibit the signs and symptoms of schizophrenia. These deficits may in fact be central to the pathophysiology underlying the development of overt psychosis in schizophrenia. The deficits appear to be relatively stable across the course of the illness. They are generally more severe in schizophrenia than in affective disorders and may have a relatively specific pattern in schizophrenia. It is concluded that the evidence that cognitive deficits are a core feature of schizophrenia is sufficiently compelling to warrant inclusion of these deficits in the diagnostic criteria for schizophrenia, at least as a nonessential criterion.     

Cognitive functioning in young people with first episode psychosis: relationship to diagnosis and clinical characteristics

OBJECTIVE: To examine the extent and nature of neuropsychological deficits in adolescents and young people with first episode psychosis (FEP), and to determine whether the pattern and extent of neuropsychological deficits varied according to diagnosis. METHOD: A total of 83 FEP subjects aged 13-25 years, and 31 healthy controls completed a comprehensive battery of neuropsychological tests, grouped into 10 cognitive domains. First episode psychosis subjects were stratified into three diagnostic groups (schizophrenia, affective disorders, substance-induced psychosis) and differences in cognitive profiles were examined. The contribution of demographic and clinical characteristics to cognitive performance was also explored. RESULTS: The schizophrenia group demonstrated significantly worse performance on tasks of verbal learning and memory than the affective disorders group. Compared to healthy controls, the schizophrenia group also demonstrated global impairment across the majority of cognitive domains. The substance-induced group's performance lay between that of the schizophrenia and affective disorders groups. Analyses of differential deficits revealed that verbal learning, verbal memory and current intellectual functioning were selectively impaired in the schizophrenia group, whereas the affective disorders group demonstrated a selective deficit in speeded processing. Premorbid intellectual functioning, negative symptomatology and medication levels were the strongest predictors of cognitive performance in FEP subjects. CONCLUSIONS: Verbal memory deficits differentiate individuals with schizophrenia from those with psychotic affective disorders. Although significant cognitive deficits are evident across all diagnostic FEP groups, individuals with schizophrenia appear to have more generalized impairment across a broad array of cognitive functions than other psychotic diagnoses. Lower premorbid intellectual functioning does not appear to contribute to greater cognitive deterioration following onset of psychosis, but severity of illness may be a more important factor than levels of mood disturbance.     

Influence of diagnostic classification on gender ratio in schizophrenia

BACKGROUND: The research literature on hospital admissions for psychoses in youths was reviewed in order to test whether there was a gender ratio discrepancy in diagnostic subgroups; the effect of the diagnostic criteria classification on this measure was also investigated. METHOD: A meta-analysis was conducted on 12 primary studies by assessing the male/female odds ratio (OR) in the schizophrenia and mood disorders with psychosis subgroups as well as the amount of variability between studies. Study inclusion criteria were: patients between the ages of 8 and 19, at least 15 patients with psychosis and a standardized diagnostic criteria classification system such as DSM, ICD or RDC. RESULTS: The male/female OR measured in this meta-analysis implies that a male subject with psychosis is 1.7 times as likely to obtain a diagnosis of schizophrenia; conversely, a female subject with psychosis is 2.1 times as likely to be assigned in the mood disorders with psychosis subgroup. Disparity in diagnostic criteria nomenclature (ICD-9 vs. DSM) could account for a statistically significant difference in male/female OR for the schizophrenia subgroup in a subset of 11 studies. CONCLUSIONS: Under the narrower definition of schizophrenia in studies using DSM diagnostic criteria classification, the shift towards a greater proportion of patients diagnosed with mood disorders with psychosis could be explained by the time criteria; the simultaneous emergence of the gender ratio difference is discussed. This study shows that subtle changes in diagnostic criteria in psychiatric illnesses can greatly influence observational data pertaining to youths.     

Comparing symptoms of autism spectrum disorders using the current DSM-IV-TR diagnostic criteria and the proposed DSM-V diagnostic criteria

The American Psychiatric Association has proposed major revisions for the diagnostic category encompassing Autism Spectrum Disorders (ASD), which will reportedly increase the specificity and maintain the sensitivity of diagnoses. As a result, the aim of the current study was to compare symptoms of ASD in children and adolescents (N = 208) who met criteria for ASD according to only the DSM-IV-TR to those who met criteria according to the forthcoming version of the DSM and to those that were typically developing. Participants comprising the DSM-IV-TR and DSM-V groups did not score significantly different from each other on overall autism symptoms, but both groups scored significantly different from the control group. However significant differences emerged between the DSM-IV-TR and DSM-V groups in the core domain of nonverbal communication/socialization. Implications of the results and the proposed changes to the ASD diagnostic category are discussed.     

Neuropsychological Performance in Older Patients With Schizophrenia: A Meta-Analysis of Cross-sectional and Longitudinal Studies

Objective: Cognitive deficits are among the most reliable predictors of functional impairment in schizophrenia and a particular concern for older individuals with schizophrenia. Previous reviews have focused on the nature and course of cognitive impairments in younger cohorts, but a quantitative meta-analysis in older patients is pending. Method: A previously used search strategy identified studies assessing performance on tests of global cognition and specific neuropsychological domains in older patients with schizophrenia and age-matched comparison groups. Both cross-sectional and longitudinal studies were included. Potential methodological, demographic, and clinical moderators were analyzed. Results: Twenty-nine cross-sectional (2110 patients, 1738 comparison subjects) and 14 longitudinal (954 patients) studies met inclusion criteria. Patients were approximately 65 years old, with 11 years of education, 53% male and 79% Caucasian. Longitudinal analysis (range 1–6 years) revealed homogeneity with small effect sizes (d = −0.097) being observed. Cross-sectional analyses revealed large and heterogeneous deficits in global cognition (d = −1.19) and on specific neuropsychological tests (d = −0.7 to −1.14). Moderator analysis revealed a significant role for demographic (age, sex, education, race) and clinical factors (diagnosis, inpatient status, age of onset, duration of illness, positive and negative symptomology). Medication status (medicated vs nonmedicated) and chlorpromazine equivalents were inconsequential, albeit underrepresented. Conclusions: Large and generalized cognitive deficits in older individuals with schizophrenia represent a robust finding paralleling impairments across the life span, but these deficits do not decline over a 1–6 year period. The importance of considering demographic and clinical moderators in cross-sectional analyses is highlighted.     

Intermittent explosive disorder: development of integrated research criteria for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

This study was designed to develop a revised diagnostic criteria set for intermittent explosive disorder (IED) for consideration for inclusion in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). This revised criteria set was developed by integrating previous research criteria with elements from the current DSM-IV set of diagnostic criteria. Evidence supporting the reliability and validity of IED-IR (“IED Integrated Criteria”) in a new and well-characterized group of subjects with personality disorder is presented. Clinical, phenomenologic, and diagnostic data from 201 individuals with personality disorder were reviewed. All IED diagnoses were assigned using a best-estimate process (eg, kappa for IED-IR >0.85). In addition, subjects meeting IED-IR criteria had higher scores on dimensional measures of aggression and had lower global functioning scores than non–IED-IR subjects, even when related variables were controlled. The IED-IR criteria were more sensitive than the DSM-IV criteria only in identifying subjects with significant impulsive-aggressive behavior by a factor of 16. We conclude that the IED-IR criteria can be reliably applied and have sufficient validity to warrant consideration as DSM-V criteria for IED.     

The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample

Cannabis use is highly prevalent among people with schizophrenia, and coupled with impaired cognition, is thought to heighten the risk of illness onset. However, while heavy cannabis use has been associated with cognitive deficits in long-term users, studies among patients with schizophrenia have been contradictory. This article consists of 2 studies. In Study I, a meta-analysis of 10 studies comprising 572 patients with established schizophrenia (with and without comorbid cannabis use) was conducted. Patients with a history of cannabis use were found to have superior neuropsychological functioning. This finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In Study II, we examined the neuropsychological performance of 85 patients with first-episode psychosis (FEP) and 43 healthy nonusing controls. Relative to controls, FEP patients with a history of cannabis use (FEP + CANN; n = 59) displayed only selective neuropsychological impairments while those without a history (FEP − CANN; n = 26) displayed generalized deficits. When directly compared, FEP + CANN patients performed better on tests of visual memory, working memory, and executive functioning. Patients with early onset cannabis use had less neuropsychological impairment than patients with later onset use. Together, these findings suggest that patients with schizophrenia or FEP with a history of cannabis use have superior neuropsychological functioning compared with nonusing patients. This association between better cognitive performance and cannabis use in schizophrenia may be driven by a subgroup of “neurocognitively less impaired” patients, who only developed psychosis after a relatively early initiation into cannabis use.     

Shared intermediate phenotypes for schizophrenia and bipolar disorder: neuroanatomical features of subtypes distinguished by executive dysfunction

Background

Shared genetic vulnerability for schizophrenia and bipolar disorder may be associated with common neuroanatomical features. In view of the evidence for working memory dysfunction as a candidate intermediate phenotype for both disorders, we explored neuroanatomical distinctions between subtypes defined according to working memory (n-back task) performance.

Methods

We analyzed T₁-weighted MRI scans for patients with schizophrenia-spectrum disorder, bipolar-I disorder (BD-I) and healthy controls. The VBM8 toolbox was used to assess differences in grey and white matter volume across traditional diagnostic groups (schizophrenia v. BD-I). Subsequently, groups were defined as “executively spared” (ES) based on the achievement of greater than 50% accuracy in the 2-back task performance (comparable to performance in the control group) or “executively deficit” (ED) based on the achievement of less than 50% accuracy.

Results

Our study included 40 patients with schizophrenia-spectrum disorders, 30 patients with BD-I and 34 controls. Both the schizophrenia and BD-I groups showed grey matter volume reductions relative to the control group, but not relative to each other. The ED subtype (n = 32 [10 BD-I, 22 schizophrenia]) showed grey matter volume reductions in the bilateral superior and medial frontal gyri, right inferior opercular gyri and hippocampus relative to controls. The ES subtype (n = 38 [20 BD-I, 18 schizophrenia]) showed grey matter volume reductions in the right precuneus and left superior and medial orbital frontal gyri relative to controls. The ED subtype showed grey matter volume reduction in the right inferior frontal and precentral gyri relative to the ES subtype. There were no significant differences in white matter volume in any group comparisons.

Limitations

This analysis was limited by small sample sizes. Further, insufficient numbers were available to assess a control-deficit comparison group. We were unable to assess the effects of mood stabilizer dose on brain structure.

Conclusion

Neuroanatomical commonalities are evident among patients with schizophrenia-spectrum disorders and BD-I with working memory deficits. Reduced inferior frontal lobe volume may mediate cognitive deficits shared across the psychosis–mood spectrum.     

Visual N80 latency as a marker of neuropsychological performance in schizophrenia: Evidence for bottom-up cognitive models

ObjectiveCognitive deficits and visual impairment in the magnocellular (M) pathway, have been independently reported in schizophrenia. The current study examined the association between neuropsychological (NPS) performance and visual evoked potentials (VEPs: N80/P1 to M- and P(parvocellular)-biased visual stimuli) in schizophrenia and healthy controls.MethodsNPS performance and VEPs were measured in n = 44 patients and n = 34 matched controls. Standardized NPS-scores were combined into Domains and a PCA (Principal Component Analysis) generated Composite. Group differences were assessed via (M)ANOVAs, association between NPS and VEP parameters via PCA, Pearson’s coefficient and bootstrapping. Logistic regression was employed to assess classification power.ResultsPatients showed general cognitive impairment, whereas group differences for VEP-parameters were non-significant. In patients, N80 latency across conditions loaded onto one factor with cognitive composite, showed significant negative correlations of medium effect sizes with NPS performance for M/P mixed stimuli and classified low and high performance with 70% accuracy.ConclusionThe study provides no evidence for early visual pathway impairment but suggests a heightened association between early visual processing and cognitive performance in schizophrenia.SignificanceOur results lend support to bottom-up models of cognitive function in schizophrenia and implicate visual N80 latency as a potential biomarker of cognitive deficits in schizophrenia.     

Stable Cognitive Deficits in Schizophrenia Patients With Comorbid Obsessive-Compulsive Symptoms: A 12-Month Longitudinal Study

Background: Amongst schizophrenia patients, a large subgroup of up to 25% also suffers from comorbid obsessive-compulsive symptoms (OCSs). The association between comorbid OCSs in these patients and neuropsychological impairment remains unclear and somewhat contradictory. Longitudinal approaches investigating the stability of OCS-associated cognitive deficits are missing. Methods: Thirty-seven patients with schizophrenia and comorbid OCSs and 43 schizophrenia patients without OCS were assessed with a comprehensive cognitive test battery and compared at baseline and, again, 12 months later. Results: Schizophrenia patients with comorbid OCSs showed significant pronounced deficits, with increasing effect sizes over the 12-month assessment period in specific cognitive areas such as visuospatial perception and visual memory (WAIS-R block design, Rey–Osterrieth Complex Figure Test), executive functioning (perseveration in the Wisconsin Card Sorting test), and cognitive flexibility (Trail Making test B). These cognitive domains are correlated with OCS severity and are known to be candidate cognitive domains in obsessive-compulsive disorder (OCD). Conclusions: OCSs in schizophrenia is associated with specific and longitudinally stable cognitive deficits, strongly arguing for at least partially overlapping neurobiological mechanisms with OCD. Prospective studies involving patients with at-risk mental states for psychosis are necessary to decipher the interaction of cognitive impairment and the clinical manifestations of schizophrenia and OCSs. This might facilitate the definition of patients at high risk for OCSs, an early detection of subclinical levels, therapeutic interventions, and clinical monitoring.Key words: schizophrenia, obsessive-compulsive symptoms, cognitive deficits, comorbidity, neuropsychology, psychosis     

Meta-analysis of Cognitive Impairment in First-Episode Bipolar Disorder: Comparison With First-Episode Schizophrenia and Healthy Controls

Neurocognitive deficits are evident both in established schizophrenia and bipolar disorder (BP). However, it has been suggested that schizophrenia, but not BP, is characterized by neurodevelopmental abnormalities that can lead to cognitive deficits at the earliest stages of the illness. The aim of this meta-analytic review was to compare neurocognitive deficits in first-episode BP (FEBP) with healthy controls and first-episode schizophrenia (FES) patients. The current meta-analysis included a total of 22 adult studies and involved comparisons of 533 FEBP patients with 1417 healthy controls and 605 FEBP and 822 FES patients. FEBP patients were significantly impaired in all cognitive domains (d = 0.26–0.80) and individual tasks (d = 0.22–0.66) investigated. FES patients significantly underperformed FEBP patients in most cognitive domains (d = 0.05–0.63) and on individual tasks (d = 0.13–0.77). Neuropsychological impairment, which is comparable to chronic BP, was evident in FEBP. Similar to chronic patients, cognitive functions in FEBP lie intermediate between FES and healthy controls. Neurodevelopmental factors are likely to play a significant role not only in schizophrenia but also in BP.Key words: bipolar disorder, cognition/mania, psychosis, schizophrenia     

Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders

Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms of intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10 criteria. A healthy control group (N = 40) was included, matched on gender and age. Cognitive functions were assessed using WISC-III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschke's selective reminding task. A similar profile and level of impairment was found on measures of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently after illness onset. Compared to the deficits of adult schizophrenia described in the literature, the results suggest relatively spared simple reaction times in early onset patients.     

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.     

The cognitive aspect of formal thought disorder and its relationship with global social functioning and the quality of life in schizophrenia

Purpose

It was expected that using a comprehensive scale like the Thought and Language Disorder Scale (TALD) for measurement of FTD would enable assessing its heterogeneity and its associations with cognitive impairment and functionality. This study has aimed to analyze the relationship between formal thought disorder (FTD) and cognitive functions, functionality, and quality of life in schizophrenia.

Methods

This cross-sectional exploratory study included 46 clinical participants meeting the DSM-5 diagnostic criteria for schizophrenia and 35 healthy individuals as the control groups. Data were acquired by means of the Turkish language version of the TALD, the Positive and Negative Syndrome Scale, the Clinical Global Impression Scale, the Functioning Assessment Short Test, the Social Functioning Scale, the World Health Organization Quality of Life Instrument-Short Form, and a neuropsychological test battery on executive functions, working memory, verbal fluency, abstract thinking, and response inhibition. Correlation analyses were conducted to detect significant relationships.

Results

The clinical group scored failures in all cognitive tests. The objective positive FTD was associated with deficits in executive functions and social functioning. The objective negative FTD was associated with poor performance in all cognitive domains, physical quality of life, and social and global functioning. The subjective negative FTD was negatively correlated with psychological quality of life.

Conclusion

This study demonstrated that objective FTD factors reflect different underlying cognitive deficits and correlate with different functioning domains. Significant correlation was determined between subjective negative FTD and psychological quality of life. Given the close relationship of FTD with functioning and quality of life, the FTD-related cognitive deficits should be the key treatment goal in schizophrenia.

     

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