An evaluation of irreversible psychosurgical treatment of patients with obsessive-compulsive disorder in the Netherlands, 2001-2008.

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.

Is there change in intelligence quotient in chronically ill schizophrenia patients? A longitudinal study in twins discordant for schizophrenia.

BACKGROUND: Intellectual 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. METHOD: We 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). RESULTS: A significant interaction effect over time was found between IQ measurement and illness (F=4.22, df=1, p<0.05), indicating that change in IQ over time is significantly different between the groups. A stable course in IQ over time was found in the patients with schizophrenia (mean IQ from 109.78 at baseline to 108.44 at follow-up) relative to both the healthy control twins who showed a small increase (from 114.61 at baseline to 119.18 at follow-up) (t=2.06, p<0.05) and the unaffected co-twins (from 111.60 to 117.60, t=-2.32, p<0.05). IQ change in the unaffected co-twins of schizophrenia patients was comparable with that in healthy control twins (t=-0.49, p=0.63). CONCLUSIONS: Patients 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.

[Postoperative cognitive dysfunction]. / Postoperatieve cognitieve disfunctie.

Memory loss and lack of concentration are symptoms that frequently occur in patients who have undergone a surgical procedure. Although cognitive function can be assessed using neuropsychological tests, diagnosing postoperative cognitive decline (POCD) reliably appears to be difficult. Therefore, the true incidence of POCD is unknown. Severe POCD, which is apparent even without neuropsychological testing, is predominantly reported after cardiac and hip-replacement surgery. In these cases, POCD probably reflects micro embolic brain injury. Apart from the nature of the surgical procedure, advanced age is the most important risk factor for POCD. The anaesthetic technique used is not a determinant: the risks of POCD occurring appear to be similar following both general and local anaesthesia.

The incidence of cognitive decline after (not) undergoing coronary artery bypass grafting: the impact of a controlled definition.

BACKGROUND: After coronary artery bypass grafting (CABG), 20-30% of patients are reported to suffer from cognitive decline. Studies reporting these high incidences, however, have not included an appropriate control group. METHODS: We repeatedly administered a series of neuropsychological tests to 112 healthy middle-aged volunteers not undergoing surgery, and applied two widely used definitions of cognitive decline to their test results. In addition, we re-analysed the neuropsychological test data of 281 CABG patients with a definition of cognitive decline that takes into account the natural variability of test performance that was found in the volunteers. RESULTS: Three months after their first assessment, 14-28% of the volunteers suffered from cognitive decline according to the definitions of cognitive decline after CABG. Using the controlled definition of cognitive decline that takes the natural variability in test performance into account, we found that only 7.7% of the CABG patients suffered from cognitive decline at 3 months after their operation. CONCLUSION: These data suggest that the incidence of cognitive dysfunction after CABG has previously been greatly overestimated.

Association between early and three month cognitive outcome after off-pump and on-pump coronary bypass surgery.

OBJECTIVE: 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. DESIGN: Randomised trial with an additional prediction study within the two randomised groups. SETTING: Three centres for heart surgery in the Netherlands. PATIENTS: 281 patients, mean age 61 years. INTERVENTIONS: Participants were randomly assigned to off-pump or on-pump coronary bypass surgery. MAIN OUTCOME MEASURES: 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. RESULTS: 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, p < 0.01) 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). CONCLUSIONS: 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.

The effect of zero-balanced ultrafiltration during cardiopulmonary bypass on S100b release and cognitive function.

Zero-balanced ultrafiltration (ZBUF) might reduce the systemic inflammatory response (SIRS) during cardiopulmonary bypass (CPB) by removing inflammatory mediators. The objective of this study was to determine the effect of ZBUF on postoperative serum S100b levels, a marker of neuronal injury. In addition, the possible effects of ZBUF on postoperative neurocognitive function were assessed. Sixty patients undergoing elective coronary bypass grafting were randomly assigned either to a control group or to a protocol group in which ZBUF was performed. Serum S100b levels were measured five minutes after intubation, at the end of bypass and eight and 20 hours after arrival at the intensive care unit (ICU). Cognitive function was assessed with neuropsychological tests on the day before the operation and the sixth day after surgery. The S100b level at 20 hours after arrival at the ICU was 0.27 g/L (SD 0.16) in the control and 0.25 g/L (SD 0.12) in the group with ZBUF. There were no statistical differences at any time between the two groups. S100b was not detectable in the ultrafiltrate, indicating that these results were not obscured by washout of S100b. Thirteen patients (52%) in the control group and 14 patients (56%) in the ZBUF group showed a cognitive deficit. In conclusion, ZBUF during CPB does not decrease the release of S100b. This result is not affected by washout. ZBUF did not reduce the incidence of early neurocognitive deficits. The role of SIRS in the development of cognitive dysfunction following CPB remains to be resolved.

[Presymptomatic detection of Parkinson's disease]. / Presymptomatische detectie van de ziekte van Parkinson.

Parkinson's disease (PD) is characterized by a progressive degeneration of mesencephalic dopaminergic neurons. More than half of these neurons are lost in a presymptomatic phase of an estimated 4-6 years duration. It is obvious that any type of treatment aimed at slowing down the disease process should preferably be applied in this presymptomatic phase. Presymptomatic detection of PD has therefore become an important goal. In a recent study in a population of 361 asymptomatic first degree relatives of PD patients, we were able to demonstrate that presymptomatic detection is possible by means of a combination of three olfactory processing tasks and [123l] beta-CIT single photon emission computed tomography (SPECT) scanning of the nigrostriatal dopaminergic system. These results are a first step towards the development of a screening strategy that may be applied in the general population. Impairments of olfactory function, however, are not specific to PD but are also associated with other neurodegenerative disorders (e.g. Alzheimer's disease) and certain lifestyle characteristics (e.g. smoking). In the next few years our research efforts will focus on two different approaches to develop a more specific screening strategy. First, olfactory processing tasks will be combined with tasks aimed at detecting subtle (visuo)motor disturbances and early cognitive impairments. In parallel, an effort will be made to define disease-specific patterns of olfactory dysfunction in neurodegenerative disorders.

Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell.

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]beta-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]beta-CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs in PD.

Neurocognitive dysfunction after coronary artery bypass surgery: a systematic review.

OBJECTIVE: Substantial, albeit scattered, evidence suggests that coronary artery bypass grafting may impair cognitive function. As methods and definitions differ greatly across studies, the reported incidence of cognitive decline after coronary bypass surgery varies widely as well. The aim of the present study was to systematically review those studies on cognitive decline that are relatively comparable and meet with certain quality criteria. METHODS: Four electronic databases and the references of several abstract books and earlier reviews were used to identify relevant literature. Stringent criteria, based in part on the 1994 consensus meeting on assessment of neurobehavioral outcomes after cardiac surgery, were used to assess the studies that were found. In total, 256 different titles were found, of which 23 met with the formulated selection criteria. RESULTS: Twelve cohort studies and eleven intervention studies were evaluated. A pooled analysis of six highly comparable studies yielded a proportion of 22.5% (95% confidence interval, 18.7%-26.4%) of patients with a cognitive deficit (a decrease of at least 1 standard deviation in at least two of nine or ten tests) 2 months after the operation. CONCLUSIONS: Neurocognitive dysfunction is a frequently occurring complication of coronary artery bypass grafting. The etiologic contribution of cardiopulmonary bypass to this complication will remain unclear until a randomized trial that directly compares off-pump and on-pump bypass surgery is carried out.

Neuropsychological dysfunctions in siblings discordant for schizophrenia.

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.

Component structure of the positive and negative syndrome scale (PANSS) in patients with recent-onset schizophrenia and spectrum disorders.

RATIONALE: Earlier studies have examined the symptom dimensions of the PANSS (Positive And Negative Syndrome Scale) in patients with chronic schizophrenia. Results have suggested that three to eight component solutions best explain underlying symptom dimensions. OBJECTIVES: To examine the component structure of the PANSS and the MADRS (Montgomery Asberg Depression Rating Scale) in young patients with recent-onset schizophrenia and related disorders and the correlations between the components of both instruments. METHODS: Symptomatology was measured in 138 patients with recent-onset schizophrenia, by administering the PANSS and the MADRS. RESULTS: Principal component analysis of the PANSS revealed five components: a positive, negative, depression, agitation-excitement and disorganisation component. The MADRS only showed one component. A high correlation was found between the depression component of the PANSS and the overall score of the MADRS (p=0.87, P<0.001). A moderate correlation was found between the PANSS negative component and the overall score of the MADRS (p=0.51, P<0.001). CONCLUSIONS: The data suggest a five component structure of the PANSS. The depression component of the PANSS seems to be a valid way of assessing depression in patients with recent-onset schizophrenia.

Odor discrimination and task duration in young and older adults.

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.

Perception, mental imagery and reality discrimination in hallucinating and non-hallucinating schizophrenic patients.

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.

Memory impairment in schizophrenia: a meta-analysis.

OBJECTIVE: Memory impairment is well documented in schizophrenia. Less is known, however, about the exact magnitude, pattern, and extent of the impairment. The effect of potential moderator variables, such as medication status and duration of illness, is also unclear. In this article, the authors presented meta-analyses of the published literature on recall and recognition memory performance between patients with schizophrenia and normal comparison subjects. METHOD: Meta-analyses were conducted on 70 studies that reported measures of long-term memory (free recall, cued recall, and recognition of verbal and nonverbal material) and short-term memory (digit span). Tests of categorical models were used in analyses of potential moderators (clinical variables and study characteristics). RESULTS: The findings revealed a significant and stable association between schizophrenia and memory impairment. The composite effect size for recall performance was large. Recognition showed less, but still significant, impairment. The magnitude of memory impairment was not affected by age, medication, duration of illness, patient status, severity of psychopathology, or positive symptoms. Negative symptoms showed a small but significant relation with memory impairment. CONCLUSIONS: This meta-analysis documented significant memory impairment in schizophrenia. The impairment was stable, wide ranging, and not substantially affected by potential moderating factors such as severity of psychopathology and duration of illness.

Volumetric analysis of frontal lobe regions in schizophrenia: relation to cognitive function and symptomatology.

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 (rs = -.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.

Effects of context on judgements of odor intensities in humans.

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.

Effect of acute and chronic treatment with desglycinamide-[Arg8]vasopressin in young male and female volunteers.

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.

Pharmacokinetics of DGAVP in plasma following intranasal and oral administration to healthy subjects.

A pharmacokinetic study was carried out to assess the bioavailability of desglycinamide-[Arg8]vasopressin (DGAVP, Org 5667). DGAVP (2 mg) was administered both intranasally and orally to healthy subjects with a treatment interval of 1 week. Blood samples were taken regularly between 15 min before and 210 min after administration and were assayed for DGAVP by radioimmunoassay. In all subjects endogenous vasopressin (AVP) levels were detectable. Peak levels of DGAVP occurred at 15 min after both treatments. The mean absorption half-life was 8.7 and 7.3 min and the mean elimination half-life was 38 and 34.6 min for the intranasal and oral route of administration, respectively. The bioavailability of orally administered DGAVP was low compared with the intranasally administered drug; the relative bioavailability of oral/nasal administration was 0.7%. The results indicate that DGAVP is absorbed rapidly after both oral and intranasal administration, but the intranasal route of administration of DGAVP is 100 times more effective in increasing plasma DGAVP levels.

Effect of a single dose of des-glycinamide-[Arg8]vasopressin or oxytocin on cognitive processes in young healthy subjects.

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.