Neuropsychological performance is related to current social and occupational functioning in veterans with posttraumatic stress disorder.

BACKGROUND: Several studies have reported deficits in both immediate and delayed recall of verbal memory in patients with posttraumatic stress disorder (PTSD). However, most of these studies had several methodological disadvantages. None of these studies assessed parameters related to social or occupational functioning. METHODS: Fifty Dutch veterans of UN peacekeeping missions (25 with PTSD and 25 without PTSD) were assessed with a comprehensive neuropsychological test battery consisting of four subtests of the Wechsler Adult Intelligence Scale-III, California Verbal-Learning Test, and the Rey Auditory Verbal-Learning Test. Veterans with PTSD were free of medication and substance abuse. RESULTS: Veterans with PTSD had similar total intelligence quotient scores compared to controls, but displayed deficits of figural and logical memory. Veterans with PTSD also performed significantly lower on measures of learning and immediate and delayed verbal memory. Memory performance accurately predicted current social and occupational functioning. CONCLUSIONS: Deficits of memory performance were displayed in a sample of medication- and substance abuse-free veterans with PTSD. Deficits in memory performance were not related to intelligence quotient, length of trauma exposure, or time since trauma exposure. This study showed that cognitive performance accurately predicted current social and occupational functioning in veterans with PTSD.

Cognitive and cardiac outcomes 5 years after off-pump vs on-pump coronary artery bypass graft surgery.

CONTEXT: Conventional coronary artery bypass graft surgery with use of cardiopulmonary bypass (on-pump CABG) is associated with excellent long-term cardiac outcomes but also with a high incidence of cognitive decline. The effect of avoiding cardiopulmonary bypass (off-pump CABG) on long-term cognitive and cardiac outcomes is unknown. OBJECTIVE: To compare the effect of off-pump CABG and on-pump CABG surgery on long-term cognitive and cardiac outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Octopus Study, a multicenter randomized controlled trial conducted in the Netherlands, which enrolled 281 low-risk CABG patients between 1998 and 2000. Five years after their surgery, surviving patients were invited for a follow-up assessment. INTERVENTION: Patients were randomly assigned to receive either off-pump (n = 142) or on-pump (n = 139) CABG surgery. MAIN OUTCOME MEASURE: The primary measure was cognitive status 5 years after surgery, which was determined by a psychologist blinded to treatment allocation who administered 10 standardized validated neuropsychological tests. Secondary measures were occurrence of cardiovascular events (all-cause mortality, stroke, myocardial infarction, and coronary reintervention), anginal status, and quality of life. RESULTS: After 5 years, 130 patients were alive in each group. Cognitive outcomes could be determined in 123 and 117 patients in the off-pump and on-pump groups, respectively. When using a standard definition of cognitive decline (20% decline in performance in 20% of the neuropsychological test variables), 62 (50.4%) of 123 in the off-pump group and 59 (50.4%) of 117 in the on-pump group had cognitive decline (absolute difference, 0%; 95% confidence interval [CI], -12.7% to 12.6%; P>.99). When a more conservative definition of cognitive decline was used, 41 (33.3%) in the off-pump group and 41 (35.0%) in the on-pump group had cognitive decline (absolute difference, -1.7%; 95% CI, -13.7% to 10.3%; P = .79). Thirty off-pump patients (21.1%) and 25 on-pump patients (18.0%) experienced a cardiovascular event (absolute difference, 3.1%; 95% CI, -6.1% to 12.4%; P = .55). No differences were observed in anginal status or quality of life. CONCLUSION: In low-risk patients undergoing CABG surgery, avoiding the use of cardiopulmonary bypass had no effect on 5-year cognitive or cardiac outcomes. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN69438133.

The five-factor model of the Positive and Negative Syndrome Scale II: a ten-fold cross-validation of a revised model.

OBJECTIVE: The lack of fit of 25 previously published five-factor models for the PANSS items, can be due to the statistics used. The purpose of this study was to use a 'new' statistical method to develop and confirm an improved five-factor model. The improved model is both complex and stable. Complex means that symptoms can have multiple factor loadings, because they have multiple causes, not because they are ill defined. Stable means that the complex structure is found repeatedly in validations. METHODS: A ten-fold cross-validation (10 CV) was applied on a large data set (N = 5769) to achieve an improved factor model for the PANSS items. The advantages of 10 CV are minimal effect of sample characteristics and the ability to investigate the stability of items loading on multiple factors. RESULTS: The results show that twenty-five items contributed to the same factor all ten validations with one item showing a consistent loading on two factors. Three items were contributing to the same factor nine out of ten validations, and two items were contributing to the same factor six to eight times. The resulting five-factor model covers all thirty items of the PANSS, subdivided in the factors: positive symptoms, negative symptoms, disorganization, excitement, and emotional distress. The five-factor model has a satisfactory goodness-of-fit (Comparative Fit Index = .905; Root Mean Square Error of Approximation = .052). CONCLUSIONS: The five-factor model developed in this study is an improvement above previously published models as it represents a complex factor model and is more stable.

The five-factor model of the Positive and Negative Syndrome Scale I: confirmatory factor analysis fails to confirm 25 published five-factor solutions.

OBJECTIVE: The aim of this study was to test the goodness-of-fit of all previously published five-factor models of the Positive and Negative Syndrome Scale (PANSS). METHODS: We used confirmatory factor analysis (CFA) with a large data set (N = 5769). RESULTS: The different subsamples were tested for heterogeneity and were found to be homogeneous. This indicates that despite variability in age, sex, duration of illness, admission status, etc., in the different subsamples, the structure of symptoms is the same for all patients with schizophrenia. Although previous research has shown that a five-factor model fits the data better than models with three or four factors, no satisfactory fit for any of the 25 published five-factor models was found with CFA. CONCLUSIONS: Variability in age, sex, admission status and duration of illness has no substantial effect on the structure of symptoms in schizophrenia. The lack of fit can be caused by ill-defined items that aim to measure several properties in a single rating. Another explanation is that well-defined symptoms can have two or more causes. Then a double or triple loading item should not be discarded, but included because the complexity of symptoms in schizophrenia is represented by these multiple loadings. Such a complex model not only needs confirmation by CFA, but also has to be proven stable. A 10-fold cross-validation is suggested to develop a complex and stable model.

Odor discrimination in patients with frontal lobe damage and Korsakoff's syndrome.

The involvement of the frontal cortex and thalamic nucleus in odor discrimination in humans was assessed. Six patients with frontal lobe brain damage, seven patients with alcoholic Korsakoff's syndrome and 16 healthy comparison subjects completed odor detection and odor discrimination tasks. Multivariate general linear modeling with age as a covariant revealed significantly decreased odor discrimination ability in frontal lobe damaged patients and marginally decreased odor discrimination ability in Korsakoff's syndrome patients as compared to the healthy comparison subjects. No deficits were found in odor detection ability. The findings suggest that in human odor discrimination, there is more involvement of cortico-cortical pathways than of thalamo-cortical pathways.

Cognitive basis of hallucinations in schizophrenia: role of top-down information processing.

Hallucinations in schizophrenia have been regarded to result from the erroneous attribution of internally generated information to an external source. Distortions in mental imagery may underlie such confusions. We investigated performance of 77 subjects on multiple behavioral measures of auditory and visual mental imagery and perception, and a measure of reality monitoring. Comparisons were made between performance of schizophrenia patients with (N=22) and without (N=35) hallucinations and matched normal comparison subjects (N=20), after controlling for attentional factors. No differences emerged on any of the mental imagery measures, nor on reality monitoring accuracy. This suggests that there is no stable disposition towards abnormal mental imagery associated with hallucinations. However, for patients with active hallucinations (N=12), hallucination severity correlated positively with a measure of imagery-perception interaction in the auditory modality, r=0.70, p=0.01. Although preliminary, this finding is consistent with recent theoretical proposals in which hallucinations have been suggested to result from an increased influence of top-down sensory expectations on conscious perception.

Cognitive self-assessment one year after on-pump and off-pump coronary artery bypass grafting.

BACKGROUND: Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidity. This is usually manifested as cognitive decline and may be caused by cardiopulmonary bypass. The primary objective of this study was to explore whether patients report more cognitive failures 1 year after CABG than preoperatively. Secondary objectives were to evaluate whether there is a difference in reported cognitive failures between patients undergoing on-pump and off-pump CABG and whether a difference between CABG patients and healthy control subjects exists. Finally the relation between objective and subjective cognitive functioning was quantified. METHODS: In this prospective study, the Cognitive Failures Questionnaire (CFQ) was assigned preoperatively and 1 year postoperatively to 81 patients who were randomly assigned to undergo off-pump (n = 45) or on-pump (n = 36) CABG. A control sample of 112 age-matched healthy subjects was included who were administered the CFQ once. RESULTS: No difference was found in the total CFQ score (p = 0.222) and CFQ worry score (p = 0.207) between 1 year after CABG and before CABG. There was no difference between on-pump and off-pump CABG (total score, p = 0.458; worry score, p = 0.563). A significant difference was found in CFQ total score between CABG patients and control subjects (p < 0.001), with control subjects reporting more cognitive failures than CABG patients. Finally, patients who showed cognitive decline in the Octopus trial did not have a higher CFQ total score (p = 0.671) and CFQ worry score (p = 0.772) than patients without cognitive decline 1 year after CABG. CONCLUSIONS: The present findings suggest that CABG does not result in a substantial proportion of patients with subjectively experienced cognitive decline 1 year after the procedure, irrespective of the type of surgical technique (on-pump versus off-pump).

Global intellectual impairment does not accelerate with age in patients with schizophrenia: a cross-sectional analysis.

Neuropsychological studies show impairment in intellectual functions in schizophrenia patients. It is still unclear, however, whether intelligence scores decline progressively during the illness as compared to healthy subjects' scores. Longitudinal studies conducted so far have been restricted to relatively short time spans. The aim of this study is to investigate whether changes in intelligence scores accelerate with age in schizophrenia patients. In a cross-sectional design, performance of four subtests of the Wechsler Adult Intelligence Scale (WAIS) was analyzed in 112 schizophrenia patients and compared to that of 70 healthy subjects, across an age span of 40 years (16-56 years). A linear regression analysis was performed. A main effect on the total ratio score of the four tests was demonstrated between the two groups. No main effect of age and no interaction effect of age with group for the total ratio score were found. The results confirm that there is global intellectual impairment in schizophrenia patients at the onset of illness but no age-accelerated decline and are consistent with the neurodevelopmental hypothesis of schizophrenia.

Cognitive and emotional characteristics of alexithymia: a review of neurobiological studies.

OBJECTIVE: To review neurobiological studies of alexithymia in order to achieve a better understanding of the relationship between alexithymia and psychosomatic diseases and psychiatric illnesses. METHODS: Neurobiological studies of alexithymia were reviewed with a special focus on how emotional and cognitive elements of alexithymia are reflected in earlier research. RESULTS: Studies that have correlated alexithymia to corpus callosum dysfunctioning have mainly found impairments in cognitive characteristics of alexithymia, whereas from studies of right hemisphere and frontal lobe deficits, it may be concluded that both cognitive and emotional characteristics of alexithymia are impaired. CONCLUSION: The fact that there is no general agreement on how to define alexithymia seems to have hampered theoretical and empirical progress on the neurobiology of alexithymia and related psychosomatic diseases and psychiatric illnesses. Alexithymia should no longer be approached as one distinct categorical phenomenon and follow-up studies should monitor subjects according to both the cognitive and emotional characteristics of alexithymia.

Schizophrenic patients without neuropsychological deficits: subgroup, disease severity or cognitive compensation?

Some schizophrenic patients do not show clinically relevant cognitive deficits. The question remains whether this represents the existence of an etiologically different subgroup, a general effect of disease severity or whether their cognitive deficits do not reach a clinical threshold due to a greater cognitive compensation ('brain reserve') capacity. A group of 23 out of 118 first onset patients was identified as cognitively normal (CN). The cognitive profile of these patients was compared with that of 45 healthy controls. Next these patients were compared with the cognitively impaired (CI) patients on obstetric complications (OCs), premorbid adjustment, age at onset, Positive and Negative Syndrome Scale ratings, social functioning and substance abuse. In addition both groups were compared on intelligence and educational level as indirect indicators of cognitive compensation capacity. There were no differences in OCs, premorbid adjustment, age at onset, psychopathology or substance abuse between the two patient groups. There was a significant difference in social functioning, which is a consequence rather than a cause of cognitive deficits. However, the CN patients scored significantly higher on measures of intelligence and educational level than the CI patients. This suggests that a difference in cognitive compensation capacity could explain the existence of a CN patient group.

Kraepelin was right: a latent class analysis of symptom dimensions in patients and controls.

Phenotypic heterogeneity within patients and controls may explain why the genetic variants contributing to schizophrenia risk explain only a fraction of the heritability. The aim of this study is to investigate quantitative and qualitative differences in psychosis symptoms in a sample including psychosis patients, their relatives, and community controls. We combined factor analysis and latent class analysis to analyze variation in Comprehensive Assessment of Symptoms and History lifetime-rated symptoms in 4286 subjects. The Wechsler Adult Intelligence Scale-Intelligence Quotient (N = 2663) and the Camberwell Assessment of Need rating scale (N = 625) were assessed in a subsample. Variation in 5 continuous dimensions (disorganization, positive, negative, mania, and depression) was accounted for by the presence of 7 homogeneous classes (Kraepelinian schizophrenia, affective psychosis, manic-depression, deficit nonpsychosis, depression, healthy, and no symptoms). Eighty-five percent of the schizophrenia patients was assigned to the Kraepelinian schizophrenia class (characterized by high scores on the 5 dimensions, low IQ, and poor outcome) while 15% was assigned to the affective psychosis class (relatively low disorganization and negative scores, normal IQ, and good outcome). In bipolar patients (91% bipolar I), 41% was assigned to the Kraepelinian schizophrenia class, 44% to the affective psychosis class, and 10% to the manic-depression class. Latent class membership was associated with intelligence in psychosis patients and in their relatives but not in community controls. In conclusion, symptom heterogeneity is more pronounced in bipolar disorder compared with schizophrenia. Reducing phenotypic heterogeneity within psychosis patients and controls may facilitate etiological research.

Effect of cannabis use on the course of schizophrenia in male patients: a prospective cohort study.

BACKGROUND: Findings on the impact of cannabis use on the course of schizophrenia are inconsistent and not conclusive. AIMS: To study the effect of cannabis use on the course of schizophrenia taking into account the effects of the quantity of cannabis use and important confounders. METHODS: Prospective cohort study with assessments of symptoms, confounders and hospitalizations at baseline, 6 month and 12 month follow up. RESULTS: In a representative cohort of 145 male patients with schizophrenia, 68 (46.9%) used cannabis. Mean age at onset of schizophrenia in cannabis using patients was significantly lower than in non-cannabis using patients. No other cross-sectional demographic or clinical differences were observed between users and non-users. In a series of longitudinal analyses, cannabis use was not associated with differences in psychopathology, but relapse in terms of the number of hospitalizations was significantly higher in cannabis using patients compared to non-cannabis using patients. CONCLUSIONS: Patients with schizophrenia using cannabis are more frequently hospitalized than non-cannabis using patients but do not differ with respect to psychopathology. Possible explanations for these findings are discussed.

Does olanzapine inhibit the psychomimetic effects of Δ9-tetrahydrocannabinol?

Δ9-Tetrahydrocannabinol (THC) produces transient psychomimetic effects in healthy volunteers, constituting a pharmacological model for psychosis. The dopaminergic antagonist haloperidol has previously been shown to reduce these effects. This placebo-controlled, cross-over study in 49 healthy, male, mild cannabis users aimed to further explore this model by examining the effect of a single oral dose of olanzapine (with dopaminergic, serotonergic, adrenergic, muscarinergic and histaminergic properties) or two oral doses of diphenhydramine (histamine antagonist) on the effects of intrapulmonarily administered THC. Transient psychomimetic symptoms were seen after THC administration, as measured on the positive and negative syndrome scale (20.6% increase on positive subscale, p<0.001) and the visual analogue scale for psychedelic effects (increase of 10.7 mm on feeling high). Following the combination of THC and olanzapine, the positive subscale increased by only 13.7% and feeling high by only 8.7 mm. This reduction of THC effects on the positive subscale failed to reach statistical significance (p=0.066). However, one-third of the subjects did not show an increase in psychomimetic symptoms after THC alone. Within responders, olanzapine reduced the effects of THC on the positive subscale (p=0.005). Other outcome measures included pharmacokinetics, eye movements, postural stability, pupil/iris ratio, and serum concentrations of cortisol and prolactin.

Central nervous system effects of haloperidol on THC in healthy male volunteers.

In this study, the hypothesis that haloperidol would lead to an amelioration of Δ9-tetrahydrocannabinol (THC)-induced 'psychotomimetic' effects was investigated. In a double-blind, placebo-controlled, partial three-way crossover ascending dose study the effects of THC, haloperidol and their combination were investigated in 35 healthy, male mild cannabis users, measuring Positive and Negative Syndrome Scale, Visual Analogue Scales for alertness, mood, calmness and psychedelic effects, saccadic and smooth pursuit eye measurements, electroencephalography, Body Sway, Stroop test, Visual and Verbal Learning Task, hormone levels and pharmacokinetics. Compared with placebo, THC significantly decreased smooth pursuit, Visual Analogue Scales alertness, Stroop test performance, immediate and delayed word recall and prolactin concentrations, and significantly increased positive and general Positive and Negative Syndrome Scale score, Visual Analogue Scales feeling high, Body Sway and electroencephalography alpha. Haloperidol reversed the THC-induced positive Positive and Negative Syndrome Scale increase to levels observed with haloperidol alone, but not THC-induced 'high' feelings. Compared with placebo, haloperidol significantly decreased saccadic peak velocity, smooth pursuit, Visual Analogue Scales mood and immediate and delayed word recall and significantly increased Body Sway, electroencephalography theta and prolactin levels. THC-induced increases in positive Positive and Negative Syndrome Scale but not in Visual Analogue Scales feeling high were reversed by haloperidol. This indicates that psychotic-like effects induced by THC are mediated by dopaminergic systems, but that other systems are involved in 'feeling high'. Additionally, the clear reductions of psychotic-like symptoms by a clinically relevant dose of haloperidol suggest that THC administration may be a useful pharmacological cannabinoid model for psychotic effects in healthy volunteers.

Cognitive outcomes five years after not undergoing coronary artery bypass graft surgery.

BACKGROUND: Patients with coronary artery disease who underwent coronary artery bypass graft surgery have a high risk of cognitive decline 5 years after the procedure. It is conceivable that this is not caused by the operation, but by natural aging. METHODS: Psychologists repeatedly administered a battery of seven neuropsychological tests with eight main variables to 112 subjects without known coronary artery disease, with a time interval of 5 years. Cognitive decline was defined as deterioration in performance beyond normal variation in at least two of the eight main variables. The incidence of cognitive decline in the control subjects was compared with the incidence of cognitive decline in the 281 participants of the Octopus Study, who underwent coronary artery bypass graft surgery 5 years earlier. Patients and control subjects were age-matched. RESULTS: After 5 years, cognitive outcome could be determined in 99 of 112 control subjects (88%) and 240 of 281 coronary artery bypass graft surgery patients (85%). Cognitive decline was present in 82 (34.2%) of 240 coronary artery bypass graft surgery patients and in 16 (16.2%) of 99 control subjects (crude odds ratio, 2.69; 95% confidence interval, 1.48 to 4.90). However, after correction for differences in age, sex, education, and baseline comorbidity between the patients and the control subjects, the odds ratio was 1.37 (95% confidence interval, 0.65 to 2.92). CONCLUSIONS: We were unable to demonstrate that patients who underwent coronary artery bypass graft surgery have more cognitive decline after 5 years than control subjects without coronary artery disease.

Caregiver burden in recent-onset schizophrenia and spectrum disorders: the influence of symptoms and personality traits.

Earlier studies that used two symptom dimensions indicate that the caregiver burden for patients with schizophrenia is significantly determined by their negative symptoms. The purpose of this study is to examine the relationship between symptom severity in recent-onset schizophrenia and caregiver burden in a more differentiated way (i.e., five-symptom dimensions). Based on previous research, which shows that patients' personality traits influence the course of schizophrenia, we theorize that personality traits could also influence caregiver burden. So far, this hypothesis has never been studied. Therefore, the second purpose of this study is to examine whether patients' personality traits would contribute to caregiver burden. The results of this study showed that the disorganization symptom component was the predicting variable of the subscales supervision, tension, urging, distress, and the overall amount of caregiver burden in a linear regression analysis. Personality traits of patients played no substantial role in caregiver burden. These findings suggest that psychoeducational programs should address the severity of disorganization symptoms to reduce caregiver burden in the early phase of schizophrenia.

Cognitive outcome after off-pump and on-pump coronary artery bypass graft surgery: a randomized trial.

CONTEXT: Coronary artery bypass graft (CABG) surgery is associated with a decline in cognitive function, which has largely been attributed to the use of cardiopulmonary bypass (on-pump procedures). Cardiac stabilizers facilitate CABG surgery without use of cardiopulmonary bypass (off-pump procedures) and should reduce the cognitive decline associated with on-pump procedures. OBJECTIVE: To compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome. DESIGN AND SETTING: Randomized controlled trial conducted in the Netherlands of CABG surgery patients enrolled from March 1998 through August 2000, with 3- and 12-month follow-up. PARTICIPANTS AND INTERVENTION: Patients scheduled for their first CABG surgery (mean age, 61 years; n = 281) were randomly assigned to off-pump surgery (n = 142) or on-pump surgery (n = 139). MAIN OUTCOME MEASURES: Cognitive outcome at 3 and 12 months, which was determined by psychologists (blinded for randomization) who administered 10 neuropsychological tests before and after surgery. Quality of life, stroke rate, and all-cause mortality at 3 and 12 months were secondary outcome measures. RESULTS: Cognitive outcome could be determined at 3 months in 248 patients. Cognitive decline occurred in 21% in the off-pump group and 29% in the on-pump group (relative risk [RR], 0.65; 95% confidence interval [CI], 0.36-1.16; P =.15). The overall standardized change score (ie, improvement of cognitive performance) was 0.19 in the off-pump vs 0.13 in the on-pump group (P =.03). At 12 months, cognitive decline occurred in 30.8% in the off-pump group and 33.6% in the on-pump group (RR, 0.88; 95% CI, 0.52-1.49; P =.69). The overall standardized change score was 0.19 in the off-pump vs 0.12 in the on-pump group (P =.09). No statistically significant differences were observed between the on-pump and off-pump groups in quality of life, stroke rate, or all-cause mortality at 3 and 12 months. CONCLUSION: Patients who received their first CABG surgery without cardiopulmonary bypass had improved cognitive outcomes 3 months after the procedure, but the effects were limited and became negligible at 12 months.