Search

BackgroundIntellectual deficits are commonly found in schizophrenia patients. These intellectual deficits have been found to be heritable. However, whether the intellectual deficits change over time and, if so, whether the change is related with an increased genetic risk for the disease are not known.MethodWe investigated change of intelligence quotient (IQ) in a twin sample of chronically ill schizophrenia patients, the discordant co-twins and healthy controls during a follow-up period of 5 years. A total of 52 twins completed two IQ assessments: nine patients [three monozygotic (MZ) and six dizygotic (DZ)], 10 unaffected co-twins (three MZ and seven DZ) and 33 healthy control twins (21 MZ and 12 DZ).ResultsA significant interaction effect over time was found between IQ measurement and illness (F=4.22, df=1, pt=2.06, pt=−2.32, pt=−0.49, p=0.63).ConclusionsPatients with schizophrenia in the chronic phase of the disease, but not the discordant co-twins, show a lack of increase in IQ, which is probably due to environmental (non-genetic) factors related to the disease.

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.

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. Depression and Anxiety, 2009. © 2008 Wiley-Liss, Inc.

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.

ContextConventional 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.ObjectiveTo compare the effect of off-pump CABG and on-pump CABG surgery on long-term cognitive and cardiac outcomes.Design, Setting, and ParticipantsThe 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.InterventionPatients were randomly assigned to receive either off-pump (n = 142) or on-pump (n = 139) CABG surgery.Main Outcome MeasureThe 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.ResultsAfter 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.ConclusionIn low-risk patients undergoing CABG surgery, avoiding the use of cardiopulmonary bypass had no effect on 5-year cognitive or cardiac outcomes.Trial Registrationisrctn.org Identifier: ISRCTN69438133

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. (c) 2006 Elsevier B.V. All rights reserved.

Admissions for irreversible psychosurgical treatment of obsessive-compulsive disorder (OCD) by the Working Group for Indication Psychosurgery in the Netherlands were analyzed, and the postsurgical effects on symptom severity and quality of life were evaluated. The data were extracted from patient records in the period 2001-2008, and there was a postoperative assessment with a semistructured interview. Fourteen patients applied, having severe OCD with mostly one or more comorbid disorders. The mean Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score was 32 points. Four of seven patients in whom psychosurgery was deemed useful were operated on. The decrease of the Y-BOCS score from registration to after surgery was 9 points (range, 3-17 points). An improvement in social function was present in three of four patients. In conclusion, psychosurgery can be a valuable treatment option for patients with severe OCD in whom other treatments fail.

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.

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.

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.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.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 (p0.001), 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.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).

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.

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 (0) 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Patients with type 2 (non-insulin dependent) diabetes mellitus may express moderate degrees of cognitive impairment. The aim of this study was to further characterise these cognitive deficits. Cognitive functions were assessed in 13 patients and 16 controls, matched for age, sex, education and occupational level. In addition, a neurological examination was performed. The performance of diabetic patients was impaired on the neuropsychological examination, in particular in tasks assessing learning and memory. Attention, motor planning and reaction time appeared to be unaffected. Symptoms and/or signs of distal symmetric polyneuropathy were detected in 31% and 56% of the diabetic patients, respectively. The observed deficits are in line with previous neuropsychological studies in type 2 diabetic patients, showing deficits in learning and memory and complex information processing. The fact that these cognitive impairments are reported consistently stresses the need to obtain further insights into pathogenic mechanisms, in order to be able to take adequate preventive measures.

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a significant loss of dopaminergic neurons has already occurred. Identifying patients in the period between the presumed onset of dopaminergic cell loss and the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effort to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmic individuals from a total of 250 relatives (parents, siblings, or children) of subjects with PD. Single photon emission computed tomography (SPECT) with [123I]β-CIT as a dopamine transporter ligand was used to assess nigrostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients. An abnormal reduction in striatal dopamine transporter binding was found in 4 out of 25 hyposmic relatives of PD patients, two of whom subsequently developed clinical parkinsonism, and in none of the 23 normosmic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives of sporadic PD patients by means of [123I] β-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Objectives. In this study the hypothesis was tested that hallucinations result from confusing external and internal stimulus sources, i.e., perception and imagery, respectively. Design and methods. Thirteen hallucinating and 19 non-hallucinating schizophrenic patients, as well as 14 control participants performed multiple tests of perception, vividness of mental imagery and the ability to discriminate between them (reality discrimination). These functions were tested in both the auditory and the visual modalities. Results. There were no group differences on perceptual acuity. The results on one imagery task indicated that for the hallucinating patients, the relative, but not the absolute, level of vividness of mental images might be higher in the auditory modality, which was the modality in which 12 of the patients also experienced hallucinations, than in the visual modality. Finally, there was a positive relationship between severity of (auditory) hallucinations and reality discrimination problems. Conclusions. Hallucinations may result from increased vividness of mental imagery, and their severity increases with larger impairments in reality discrimination. It is recommended that research into, and cognitive behavioural therapy for, hallucinations should also focus on their sensory qualities.

Although cognitive impairments are well recognized in patients with schizophrenia, it is unclear which impairments are due to a genetic predisposition and which are caused by secondary disease effects or phenotype. The aim of this study is to investigate the possible relationship between genetic vulnerability to schizophrenia and cognitive functioning. Three groups of subjects were compared: 14 patients with schizophrenia, 15 healthy siblings and 32 healthy control subjects. All subjects were tested neuropsychologically. The raw test data were rescaled to standard equivalents (z-scores). Subjects' z scores on tests assessing the same cognitive domain were clustered and analyzed. Differences in cognitive functioning were found in the domains of abstraction, attention, executive functioning, spatial memory, and sensory-motor functioning. The schizophrenic probands were impaired on all these five domains whereas the healthy probands showed impairments on executive functioning and partially on sensory-motor functioning. Furthermore, for spatial memory the significant finding could mainly be attributed to impaired functioning in the patients, but not healthy siblings or control subjects, whereas for executive functioning patients and healthy siblings seemed equally impaired as compared to control subjects. The planning time of the Tower of London (TOL) and the initiation time of the Motor Planning Task (MPT) were used for measures of executive functioning, while the 'time to move of the Motor Planning Task' was used as measures of sensory motor functioning. These results suggest that the cognitive abnormalities in schizophrenia that may be related to genotype are represented in the domain of executive functioning and to some extent in the domain of sensory-motor functioning.

Background: The purpose of this study was to examine the structure of dorsolateral, medial, and orbital regions of the frontal lobe in schizophrenia, and to determine whether their volumetric measurements were related to cognitive function and symptomatology. Methods: High resolution magnetic resonance imaging scans of the brains of 14 schizophrenic patients and 14 closely matched healthy controls were acquired. Volumes of gray and white matter of the left and right dorsolateral, medial, and orbital prefrontal brain regions were measured. Tests of verbal and visual memory and executive functions were used to assess cognitive function. The SANS and SAPS were used to obtain symptom ratings in patients. Results: Data of 13 schizophrenic patients were analyzed. Patients showed a general, though not significant, decrease in volumes of frontal regions as compared to controls. In patients, but not in controls, smaller left and right prefrontal gray matter volumes were significantly correlated with impaired performance on immediate recall in verbal and visual memory and semantic fluency. Furthermore, in patients, smaller total orbitofrontal gray matter volume was significantly correlated with more severe negative symptomatology (r s = −.76, p = .006). Conclusions: These findings suggest that in schizophrenia, deficits in verbal and visual memory and semantic fluency and negative symptoms may be related to (subtle) abnormalities in frontal lobe structure.

This study evaluated whether the intensity of previously smelled odors could unintentionally influence the subsequent judgement of odor intensity. The predicted context effect was based on the adaptation-level theory. Before and 25 min after either WEAK or STRONG biasing odor concentrations, 51 subjects were required to rate the intensity of 10 different odor concentrations of California Orange Oil. After the WEAK bias, subjects judged the odor intensity as being stronger than they did after the STRONG bias. Thus the intensity of odors smelled 25 min earlier can unintentionally influence subsequent odor intensity judgement. The findings are discussed in the light of two alternative explanations, namely, a central implicit memory process and a stimulus-level-based change at the peripheral level.

In this review some issues in the domain of human memory research are discussed. Recent neuropsychological data on topics such as declarative memory, procedural memory and episodic retrieval of information are highlighted. A plea is done to use other modalities in memory research, e.g. olfaction, than auditorily and visually presented stimuli alone. Functional imaging in which visuospatial and verbal working memory tasks are used have been reviewed. The role of the double dissociation paradigm in memory research has been stressed, especially in the convergence of data from neuropsychological studies and imaging studies.

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

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, p0.001) 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.

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. (C) 2012 Elsevier B.V. All rights reserved

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.

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. (c) 2006 Elsevier B.V All rights reserved.

To describe the association between cognitive outcome in the first postoperative week and that at three months after both off-pump and on-pump coronary bypass surgery, and to make a direct comparison of early cognitive outcome after off-pump versus on-pump surgery.Randomised trial with an additional prediction study within the two randomised groups.Three centres for heart surgery in the Netherlands.281 patients, mean age 61 years.Participants were randomly assigned to off-pump or on-pump coronary bypass surgery.Cognitive outcome, assessed by psychologists who administered neuropsychological tests one day before and four days and three months after surgery. A logistic regression model was used to study the predictive association between early cognitive outcome, together with eight clinical variables, and cognitive outcome after three months.Cognitive outcome in the first week after surgery was determined for 219 patients and was a predictor of cognitive decline after three months. This association was stronger in on-pump patients (odds ratio (OR) 5.24, p0.01) than in off-pump patients (OR 1.80, p = 0.23). Early decline was present in 54 patients (49%) after off-pump surgery and 61 patients (57%) after on-pump surgery (OR 0.73, p = 0.25).In patients undergoing first time coronary bypass surgery, early cognitive decline predicts cognitive outcome after three months. Early cognitive decline is not significantly influenced by the use of cardiopulmonary bypass.

To review neurobiological studies of alexithymia in order to achieve a better understanding of the relationship between alexithymia and psychosomatic diseases and psychiatric illnesses.Neurobiological studies of alexithymia were reviewed with a special focus on how emotional and cognitive elements of alexithymia are reflected in earlier research.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.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.

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.To compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome.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.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).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.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.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.

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 a-Lis 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.

The effect of task duration on odor discrimination in aging was studied. Twenty-seven young male adults and 24 young female adults between 18 and 30 years of age, and 17 older male adults between 45 and 65 years of age completed an odor discrimination task. The odor discrimination task consisted of two parts of 16 trials each in which, from three bottles consisting of two identical and one aberrant odor, the aberrant odor had to be identified. The two parts were identical except that the aberrant odor was interchanged with the identical odors in the second as compared with the first part. Results revealed a decrease in odor discrimination with age. Moreover, with increased task duration odor discrimination performance decreased considerably in older male adults while it remained unchanged in young male adults. In addition, in young adults a small advantage in females as compared with males was found in the first part of the odor discrimination task, but this effect disappeared with increased task duration. In conclusion, task duration should be taken into consideration as a factor influencing odor discrimination in aging.

A single dose of DGAVP (2 mg) and a chronic treatment of 2 weeks (1 mg/day) were given to male and female volunteers by the intranasal route. Memory, mood, vigilance, and attention were tested starting 60 min after treatment. Initial storage of abstract words was improved in the males but not in the females after chronic treatment with DGAVP. This effect persisted after discontinuation of treatment. Initial storage and learning of concrete words were not affected by treatment with DGAVP. Chronic, but not acute, treatment with DGAVP reduced the reaction time for scanning of digits in a memory comparison task (Sternberg paradigm) in both sexes. No treatment effects were found for visual memory, vigilance, attention, mood, or blood pressure. The present study indicates a sexual dimorphism in the effect of DGAVP on certain memory processes.

A single dose of des-glycinamide-[Arg8]vasopressin (DGAVP, 2 mg intranasal) or oxytocin (OXT, 20 IU intranasal) was given to female and male volunteers, respectively, in a placebo-controlled double-blind trial. Memory, vigilance, attention, and mood were tested starting 10 minutes after treatment. The DGAVP dose improved delayed recognition of abstract words when measured 1 week after treatment and reduced the intercept of a memory comparison task (Sternberg paradigm). A trend was present for DGAVP and OXT to affect learning, i.e., storage processes of verbal memory in an opposite way; DGAVP improved, while OXT attenuated initial storage and the rate of storage. No treatment effects on visual memory and vigilance were found. Of the mood measures, vigor was reduced immediately after treatment with OXT.

A series of five consecutive clinical trials were performed in which the neuropeptide desglycinamide‐(Arg8)‐vasopressin (DGAVP) was administered to human subjects suffering from cognitive and memory complaints. The patients selected for the study were carefully screened with the aid of neuropsychological assessment procedures. The trials were conducted according to a structured design in which the variables ‘dose’, ‘route of administration’, ‘treatment schedule’, ‘diagnostic group’, and ‘severity of deficit’ were varied from trial to trial in order to find optimal conditions for the possible expression of a peptide effect. The results indicate a statistically significant effect of DGAVP on word list learning in patients with mild brain trauma, suggesting that learning performance and memory retrieval are improved after peptide treatment in these patients. Patients with more severe brain trauma did not respond to peptide treatment. Some DGAVP effects, e.g. increased speed of memory search, were observed in patients with age‐associated memory deficits.

Four tasks relying on short-term retention, i.e. digit span, missing scan, randomization span, and pointing span were presented to patients with frontal-lobe lesions and normal controls. Digit span was considered a measure of passive short-term memory, the other three tasks additionally reflect comparison processes, and two of these, the randomization and pointing spans, also measure active ordering by the subject. The results confirmed Petrides and Milner's (Neuropsychologia20, 249–262, 1982) hypothesis that frontal-lobe patients are typically deficient in subject-ordered tasks. It is also suggested that they are deficient in a spontaneous generation, rather than comparison, component of subjective ordering.

ContextCoronary 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.ObjectiveTo compare the effect of CABG surgery with (on-pump) and without (off-pump) cardiopulmonary bypass on cognitive outcome.Design and SettingRandomized 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 InterventionPatients 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 MeasuresCognitive 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.ResultsCognitive 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.ConclusionPatients 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.

In animals, vasopressin and related peptides are present in specific neuronal pathways in the brain and modulate brain processes. It has been suggested that in particular memory processes, including consolidation and retrieval, short and long term memories are facilitated by vasopressin. Evidence has been presented that endogenous vasopressin is involved in these processes. But also other effects of these peptides e.g. an attenuation of acquisition of heroin self-administration have been reported. Vasopressin and related peptides have been administered to humans in a number of studies including volunteers and various patient populations with and without complaints about memory. Beneficial effects on several aspects of memory, learning, attention and concentration have been found, but not in all studies. Patients with severe deficits seem to benefit less from the peptide treatment. This may be related to the amount of brain damage. Beneficial effects of vasopressin treatment have been reported in schizophrenics and heroin addicts. In addition effects on social behavior, energy and mood of certain patients have been noted. The target patient population for vasopressin neuropeptide is thus not yet well defined. With respect to cognitive disorders, sophisticated neuropsychological test procedures, including information-processing tasks, may contribute to define such a patient population. These tasks may also be applied for treatment evaluation. It should however be kept in mind that other interesting influences of vasopressin e.g. on social behavior, mood and addictive behavior, may also appear of clinical significance. Future studies in humans may yield more detailed information in this respect. Desglycinamide (Arg8)-vasopressin or the recently discovered potent fragments of vasopressin may be recommended for these studies, because these peptides are practically devoid of the peripheral “side” effects on water homeostasis and blood pressure accompanying treatment with vasopressin or desamino-(D-Arg8)vasopressin (DDAVP).