Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for DSM-V Criteria and Beyond

It has recently been suggested that the diagnostic criteria of schizophrenia should include specific reference to cognitive impairments characterizing the disorder. Arguments in support of this assertion contend that such inclusion would not only serve to increase the awareness of cognitive deficits in affected patients, among both clinicians and researchers alike, but also increase the “point of rarity” between schizophrenia and mood disorders. The aim of the current article is to examine this latter assertion in light of the recent opinion piece provided by Keefe and Fenton (Keefe RSE, Fenton WS. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull. 2007;33:912–920). Through literature review, we explore the issue of whether cognitive deficits do in fact differentiate the major psychoses. The overall results of this inquiry suggest that inclusion of cognitive impairment criteria in Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (DSM-V) would not provide a major advancement in discriminating schizophrenia from bipolar disorder and affective psychoses. Therefore, while cognitive impairment should be included in DSM-V, it should not dictate diagnostic specificity—at least not until more comprehensive evidence-based reviews of the current diagnostic system have been undertaken. Based on this evidence, we consider several alternatives for the DSM-V definition of cognitive impairment in schizophrenia, including (1) the inclusion of cognitive impairment as a specifier and (2) the definition of cognitive impairment as a dimension within a hybrid categorical-dimensional system. Given the state of current evidence, these possibilities appear to represent the most parsimonious approaches to the inclusion of cognitive deficits in the diagnostic criteria of schizophrenia and, potentially, of mood disorders.     

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.     

Cognitive Predictors of Social and Occupational Functioning in Early Psychosis: A Systematic Review and Meta-analysis of Cross-Sectional and Longitudinal Data

Many individuals with early psychosis experience impairments in social and occupational function. Identification of modifiable predictors of function such as cognitive performance has the potential to inform effective treatments. Our aim was to estimate the strength of the relationship between psychosocial function in early psychosis and different domains of cognitive and social cognitive performance. We conducted a systematic review and meta-analysis of peer-reviewed, cross-sectional, and longitudinal studies examining cognitive predictors of psychosocial function. Literature searches were conducted in PsycINFO, PubMed, and reference lists of relevant articles to identify studies for inclusion. Of the 2565 identified, 46 studies comprising 3767 participants met inclusion criteria. Separate meta-analyses were conducted for 9 cognitive domains. Pearson correlation values between cognitive variables and function were extracted. All cognitive domains were related to psychosocial function both cross-sectionally and longitudinally. Importantly, these associations remained significant even after the effects of symptom severity, duration of untreated psychosis, and length of illness were accounted for. Overall, general cognitive ability and social cognition were most strongly associated with both concurrent and long-term function. Associations demonstrated medium effect sizes. These findings suggest that treatments targeting cognitive deficits, in particular those focusing on social cognition, are likely to be important for improving functional outcomes in early psychosis.     

Cognitive functions in bipolar affective disorder and schizophrenia: comparison

Aims: Earlier comparisons of cognitive impairment among patients with bipolar disorder and schizophrenia have found a largely similar profile of deficits, but results have varied between studies. This prompted the current attempt at another such comparison. Methods: Executive functions, memory, IQ, attention–concentration and perceptuomotor function were assessed in 48 bipolar disorder patients with operationally defined euthymia, and compared with 32 schizophrenia patients in remission, and 23 normal controls. Comparisons were re‐attempted after controlling for years of schooling and residual affective symptoms. Results: Uncontrolled comparisons indicated that, compared to controls, both bipolar disorder and schizophrenia patients were significantly impaired on different tests of executive function, memory, IQ and perceptuomotor functions. Controlling for years of schooling and residual affective symptoms, however, served to remove most of the differences between patients and controls, apart from some aspects of executive function in schizophrenia and memory impairment in both schizophrenia and bipolar disorder. Patients with schizophrenia consistently performed worse than patients with bipolar disorder, but none of the differences between schizophrenia and bipolar disorder were significant. Conclusions: Patients with bipolar disorder exhibit cognitive difficulties that are very similar to schizophrenia in terms of their profile, although patients with schizophrenia may have more severe and widespread impairments. The resemblance in cognitive profiles has important implications for the etiology and treatment of both disorders.     

Cognitive decline in elderly bipolar disorder patients: a follow‐up study

Schouws SNTM, Stek ML, Comijs HC, Dols A, Beekman ATF. Cognitive decline in elderly bipolar disorder patients: a follow‐up study. Bipolar Disord 2012: 14: 749–755. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Older individuals with bipolar disorder may exhibit greater cognitive decline over time compared to mentally healthy elderly individuals. We aimed to investigate neurocognitive performance in bipolar disorder over a period of two years. Methods: A comprehensive neuropsychological test battery was applied at baseline and two years later to 65 euthymic elderly outpatients with bipolar disorder (mean age = 68.35, range: 60–90 years) and to a demographically comparable sample of 42 healthy elderly controls. A general linear model was used to measure changes over time for the two groups. The impact of baseline illness characteristics on intra‐individual change in neurocognitive performance within the bipolar group was studied by using logistic regression analysis. Results: At baseline and at follow up, bipolar disorder patients performed worse on all neurocognitive measures compared to the healthy elderly group. However, there was no significant group‐by‐time interaction between the bipolar disorder patients and the comparison group. Conclusions: Although older bipolar disorder patients have worse cognitive function than normal controls, they did not have greater cognitive decline over a period of two years.     

Dynamic and Static Cognitive Deficits in Schizophrenia and Bipolar Disorder After the First Episode

Few studies have comprehensively examined the profile of cognitive functioning in first episode psychosis patients throughout the lifespan, and from first episode to chronic stage. We assessed functioning in general and specific cognitive functions, comparing both schizophrenia (N = 64) and bipolar I (N = 19) patients to controls (N = 103). Participants were from a population-based, case-control study of first episode psychosis patients, who were followed prospectively up to 10 years post first admission. A cognitive battery was administered at baseline and follow-up. By combining longitudinal and cross-sectional data, we were able to examine the cognitive profile of patients and controls throughout the entire age range of our sample (16–65). Schizophrenia patients exhibited widespread declines in IQ, executive function, visual memory, language ability, and verbal knowledge. However, the ages at which these declines occurred differed between functions. Deficits in verbal memory, working memory, processing speed, and visuospatial ability, on the other hand, were present at the first episode, and remained relatively static thereafter. Bipolar I patients also showed declines in IQ, verbal knowledge, and language ability, albeit at different ages to schizophrenia patients and only in verbal functions. Deficits on measures of verbal memory, processing speed, and executive function remained relatively static. Thus, both schizophrenia and bipolar I patients experienced cognitive decline in general and specific functions after the first episode, but the age at which these declines occurred differed between disorder and function. Cognitive remediation efforts may be most fruitful when targeting individual functions during specific time periods throughout adulthood.     

Cognitive functioning in euthymic bipolar I and bipolar II patients

Objective: There is growing evidence of cognitive impairment as a trait factor in bipolar disorder. The generalizability of this finding is limited because previous studies have either focussed exclusively on bipolar I disorder or have analysed mixed patient groups. Thus, it is still largely unknown whether bipolar II patients perform differently from bipolar I patients on measures of cognitive functioning. Methodology: A total of 65 patients with bipolar I disorder, 38 with bipolar II disorder, and 62 healthy controls participated in the study. Patients had to be euthymic for at least one month. Clinical and demographic variables were collected in a clinical interview and with the Structured Clinical Interview for DSM‐IV. Cognitive functioning was assessed using a neuropsychological battery. Univariate and multivariate analyses of variance were conducted for analyzing possible differences between the groups. Results: The multivariate analysis of covariance (MANCOVA) indicated overall differences in neuropsychological performance between the three groups (Pillai Spur: F 1.96, p = 0.003). Post hoc comparisons revealed that patients with bipolar I disorder showed significantly lower scores in psychomotor speed, working memory, verbal learning, delayed memory, and executive functions than healthy controls. Patients with bipolar II disorder showed significant deficits in psychomotor speed, working memory, visual/constructional abilities, and executive functions compared to controls, but not on verbal learning and delayed memory. The two patient groups did not differ significantly from each other on any domain tested. Conclusion: These results support a similar pattern of cognitive deficits in both subtypes of bipolar disorder.     

Cognitive functioning in elderly patients with early onset bipolar disorder

BACKGROUND: Very little is known about the long term cognitive sequelae of bipolar disorder. AIM: To investigate neuropsychological functioning in older euthymic persons with early onset bipolar disorder. METHOD: Fifteen older patients (age >60) with an early onset (<50 years) bipolar-I disorder in a euthymic mood were tested using a comprehensive neuropsychological test battery. Neuropsychological functioning was compared with that of a sex, age and education-matched group of 15 comparison subjects without mood disorders or memory complaints. RESULTS: Bipolar subjects scored lower than comparison subjects on selective attention, verbal memory, verbal fluency and mental effort tests. CONCLUSIONS: The findings suggest that euthymic bipolar patients are impaired across a range of cognitive domains. This could represent a trait-like cognitive disability related to the disease, as the impairments are comparable with those found in younger bipolar patients.     

Blood Groups Affective Disorders

Abstract: Distributions of seven blood groups (ABO, MNSs, P, Rh, Duffy, Kidd and Xg) were studied in a total of 118 Japanese patients with affective disorders. The patients were diagnosed according to the DSM-III (1) Major Depression (= Unipolar Disorder, UP) (2) Bipolar Disorder (BP) (3) Other Affective Disorders.
The following results were found (1) a high frequency of the B blood group in all patients with affective disorders compared with controls; (2) a high frequency of the Fy(a + b +) a low frequency of the Fy(a + b −) in all patients with affective disorders, UP BP compared with controls; (3) a low frequency of the Jk(a + b +) a high frequency of the Jk(a + b −) in BP compared with controls with UP.     

Investigating the association between neurocognition and psychosis in bipolar disorder: further evidence for the overlap with schizophrenia

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder. Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first‐degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first‐degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives. Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance. Conclusions: The finding of similar psychosis‐cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.     

Development and Validation of a Computerized Adaptive Assessment Tool for Discrimination and Measurement of Psychotic Symptoms

ObjectiveTime constraints limit the use of measurement-based approaches in research and routine clinical management of psychosis. Computerized adaptive testing (CAT) can reduce administration time, thus increasing measurement efficiency. This study aimed to develop and test the capacity of the CAT-Psychosis battery, both self-administered and rater-administered, to measure the severity of psychotic symptoms and discriminate psychosis from healthy controls.MethodsAn item bank was developed and calibrated. Two raters administered CAT-Psychosis for inter-rater reliability (IRR). Subjects rated themselves and were retested within 7 days for test-retest reliability. The Brief Psychiatric Rating Scale (BPRS) was administered for convergent validity and chart diagnosis, and the Structured Clinical Interview (SCID) was used to test psychosis discriminant validity.ResultsDevelopment and calibration study included 649 psychotic patients. Simulations revealed a correlation of r = .92 with the total 73-item bank score, using an average of 12 items. Validation study included 160 additional patients and 40 healthy controls. CAT-Psychosis showed convergent validity (clinician: r = 0.690; 95% confidence interval [95% CI]: 0.610–0.757; self-report: r = .690; 95% CI: 0.609–0.756), IRR (intraclass correlation coefficient [ICC] = 0.733; 95% CI: 0.611–0.828), and test-retest reliability (clinician ICC = 0.862; 95% CI: 0.767–0.922; self-report ICC = 0.815; 95%CI: 0.741–0.871). CAT-Psychosis could discriminate psychosis from healthy controls (clinician: area under the receiver operating characteristic curve [AUC] = 0.965, 95% CI: 0.945–0.984; self-report AUC = 0.850, 95% CI: 0.807–0.894). The median length of the clinician-administered assessment was 5 minutes (interquartile range [IQR]: 3:23–8:29 min) and 1 minute, 20 seconds (IQR: 0:57–2:09 min) for the self-report.ConclusionCAT-Psychosis can quickly and reliably assess the severity of psychosis and discriminate psychotic patients from healthy controls, creating an opportunity for frequent remote assessment and patient/population-level follow-up.     

Cognition and disability in bipolar disorder: lessons from schizophrenia research

Harvey PD, Wingo AP, Burdick KE, Baldessarini RJ. Cognition and disability in bipolar disorder: lessons from schizophrenia research.
Bipolar Disord 2010: 12: 364–375. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Background: Cognitive and functional impairments occur in patients diagnosed with bipolar disorder (BPD), although they are usually less severe and far less studied than in schizophrenia. There may be value in applying approaches developed in schizophrenia research to study cognitive functioning among BPD patients in areas including performance‐based disability assessment, cognitive remediation treatments, enhancement of the accuracy of real‐world functioning, and studying cognition and disability in relatives. Methods: We reviewed current research on cognitive and functional disability in BPD, noted areas of similarity and discrepancy to research on schizophrenia, and highlighted methods and approaches used to study schizophrenia that can be applied to study unmet needs of BPD patients. Results: Research in schizophrenia increasingly separates potential functional capacity from real‐world outcome status, and has assessed contributions of cognitive impairment and other illness factors to functional outcomes. For schizophrenia, various behavioral and pharmacological treatments aimed at cognitive enhancement have been attempted, with moderate success, compared to rare studies of treatment effects on cognitive impairment in BPD. Very little research has been performed in the occurrence of cognitive impairments in first‐degree relatives of people with BPD, despite evidence that cognitive impairments may be stable traits across symptomatic status in people with BPD. Conclusions: Research and treatment approaches developed for schizophrenia can productively be applied to the study and treatment of patients diagnosed with BPD, notably including studies of the characteristics of and treatments for functional impairment related to cognitive deficits.     

Serum calcium-independent phospholipase A2 activity in bipolar affective disorder

OBJECTIVE: Phospholipases A2 (PLA2) are a family of enzymes involved in membrane phospholipid metabolism and cell signalling. The gene encoding one form, type VI calcium-independent phospholipase A2, is located in a region of DNA that may contain a gene important in the aetiology of psychosis. Moreover, the activity of calcium-independent PLA2 is reported to be elevated in the blood and brain of patients with schizophrenia. In this study we determined whether a similar change takes place in patients with bipolar disorder with and without a history of psychosis. METHODS: Serum calcium-independent and -dependent PLA2 activities were determined in 24 patients with bipolar I disorder. RESULTS: Serum calcium-independent and -dependent PLA2 activities in bipolar cases did not differ significantly from that in healthy volunteers (HVs). However, calcium-independent PLA2 activity was significantly (p < 0.05) higher in patients with a history of psychosis compared with those with no history of psychosis (by 55%) or to HVs (by 31%). CONCLUSIONS: Our data suggest that a subset of bipolar I disorder patients with a history of psychosis have elevated calcium-independent PLA2 activity. Given that this enzyme activity is also increased in schizophrenia, elevated rates of phospholipid turnover mediated by the enzyme could represent a common biochemical feature of psychotic illness.