Håkan Nyman

Capsulotomy for obsessive-compulsive disorder: long-term follow-up of 25 patients.

CONTEXT Capsulotomy is sometimes used as a treatment of last resort in severe and treatment-refractory cases of obsessive-compulsive disorder (OCD). OBJECTIVE To evaluate the long-term efficacy and safety of capsulotomy in OCD. DESIGN Noncontrolled, long-term follow-up trial (mean of 10.9 years after surgery). SETTING University hospital referral center. PATIENTS Twenty-five consecutive patients with OCD who underwent capsulotomy from 1988 to 2000. INTERVENTION Unilateral or bilateral capsulotomy. Lesions were created by means of radiofrequency heating (thermocapsulotomy) or gamma radiation (radiosurgery, gammacapsulotomy). MAIN OUTCOME MEASURE Yale-Brown Obsessive-Compulsive Rating Scale (Y-BOCS) score. RESULTS The mean Y-BOCS score was 34 preoperatively and 18 at long-term follow-up (P < .001). Response (defined as > or = 35% reduction at long-term follow-up compared with baseline) was seen in 12 patients at long-term follow-up. Nine patients were in remission (Y-BOCS score, < 16) at long-term follow-up. Only 3 patients were in remission without adverse effects at long-term follow-up. Response rates did not differ significantly between surgical methods. A mean weight gain of 6 kg was reported in the first postoperative year. Ten patients were considered to have significant problems with executive functioning, apathy, or disinhibition. Six of these 10 patients had received high doses of radiation or had undergone multiple surgical procedures. Results of our magnetic resonance imaging analysis in 11 patients suggest that the OCD symptom reduction may be increased by reducing the lateral extension of the lesions, and a reduction in the medial and posterior extension may limit the risk of adverse effects (ie, smaller lesions may produce better results). CONCLUSIONS Capsulotomy is effective in reducing OCD symptoms. There is a substantial risk of adverse effects, and the risk may vary between surgical methods. Our findings suggest that smaller lesions are safer and that high radiation doses and multiple procedures should be avoided.

Investigating relationships between cortical thickness and cognitive performance in patients with schizophrenia and healthy adults

Relationships between prefrontal and temporal lobe grey matter volumes as assessed by magnetic resonance imaging and neurocognitive test results have been reported in schizophrenia. This investigation aimed to localize brain regions where cortical thickness and neurocognitive performance were related, and investigate if such relationships might differ in schizophrenia patients and healthy controls. Sixty-seven patients with schizophrenia and 69 healthy controls were characterized by neurocognitive testing and by brain cortical thickness maps. Putative cortical thickness/cognitive score relationships were investigated with contrast analyses of general linear models for the combined sample. Regions in which relationships were present were further investigated for diagnostic interaction. In the combined sample, significant positive relationships were found between frontal, temporal and occipital regions and tests for verbal IQ, verbal learning and executive functions. Diagnostic interaction was found for the relationships between verbal IQ and the right temporo-occipital junction and the left middle occipital gyrus. In conclusion, the significant relationships between cortical thickness and neurocognitive performances were localized in brain areas known to be involved in cognition. The relationships were similar in patients and controls, except for the right temporo-occipital and left occipital cortical areas, indicating a disrupted structure-function relationship in patients with schizophrenia compared to healthy control subjects.

Morphological correlates to cognitive dysfunction in Schizophrenia as studied with Bayesian regression

BackgroundRelationships between cognitive deficits and brain morphological changes observed in schizophrenia are alternately explained by less gray matter in the brain cerebral cortex, by alterations in neural circuitry involving the basal ganglia, and by alteration in cerebellar structures and related neural circuitry. This work explored a model encompassing all of these possibilities to identify the strongest morphological relationships to cognitive skill in schizophrenia.MethodsSeventy-one patients with schizophrenia and sixty-five healthy control subjects were characterized by neuropsychological tests covering six functional domains. Measures of sixteen brain morphological structures were taken using semi-automatic and fully manual tracing of MRI images, with the full set of measures completed on thirty of the patients and twenty controls. Group differences were calculated. A Bayesian decision-theoretic method identified those morphological features, which best explained neuropsychological test scores in the context of a multivariate response linear model with interactions.ResultsPatients performed significantly worse on all neuropsychological tests except some regarding executive function. The most prominent morphological observations were enlarged ventricles, reduced posterior superior vermis gray matter volumes, and increased putamen gray matter volumes in the patients.The Bayesian method associated putamen volumes with verbal learning, vigilance, and (to a lesser extent) executive function, while caudate volumes were associated with working memory. Vermis regions were associated with vigilance, executive function, and, less strongly, visuo-motor speed. Ventricular volume was strongly associated with visuo-motor speed, vocabulary, and executive function. Those neuropsychological tests, which were strongly associated to ventricular volume, showed only weak association to diagnosis, possibly because ventricular volume was regarded a proxy for diagnosis. Diagnosis was strongly associated with the other neuropsychological tests, implying that the morphological associations for these tasks reflected morphological effects and not merely group volumetric differences. Interaction effects were rarely associated, indicating that volumetric relationships to neuropsychological performance were similar for both patients and controls.ConclusionThe association of subcortical and cerebellar structures to verbal learning, vigilance, and working memory supports the importance of neural connectivity to these functions. The finding that a morphological indicator of diagnosis (ventricular volume) provided more explanatory power than diagnosis itself for visuo-motor speed, vocabulary, and executive function suggests that volumetric abnormalities in the disease are more important for cognition than non-morphological features.

Effects of adjuvant treatment on cognitive function in women with early breast cancer.

PURPOSE Whether adjuvant therapy impairs cognitive function in women with breast cancer (BC) is unclear. We determined the effects of adjuvant therapy on cognitive function in women with early BC. METHODS We consecutively and prospectively enrolled women aged 40-69 years who had a positive radiographic finding from the mammography screening program at Stockholm South General Hospital. All women completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention before diagnosis (T1), after surgery and before adjuvant treatment (T2), 6 months after start of adjuvant treatment (T3), and after another 3 months of follow-up (T4). Women with BC were divided into those receiving chemotherapy, hormone therapy, or no adjuvant medical therapy. Women without a diagnosis of BC served as healthy controls. RESULTS Of the 146 women enrolled, 77 had BC of whom 18 received chemotherapy; 45, hormone therapy, and 14, no adjuvant medical therapy; 69 were healthy controls. Memory scores for women with BC were significantly lower than those for controls over time, even after controlling for age and education. Memory and response speed scores were lower after chemotherapy than before (P<0.01 for both). Processing speed and attention improved significantly over time in all groups, a result consistent with a practice effect. CONCLUSION Our results indicate subtle changes related to time course and treatment. Especially, that chemotherapy may impair memory and response speed in women with BC, consistent with those reported by BC survivors after adjuvant medical treatment.

Neurocognitive function in long-term treated schizophrenia: A five-year follow-up study

Neurocognitive deficits are a core feature of schizophrenia. Deficits covering a wide range of functions have been well documented. However there is still a lack of longitudinal studies regarding the development of neurocognitive impairment. The current study examined the effect of time in long-term treated patients with schizophrenia and healthy controls on cognitive functions. A neurocognitive test-battery was administered to 36 patients and 46 controls on two occasions with approximately 4.5 years interval. Patients performed significantly worse on all measures on both occasions. The only significant decline over time was the ability to shift mental set between different rules or categories (measured by Trail Making Test B). This decline was present in both patients and controls. Improvement on attention (tested by Continuous Performance Test) was found in patients only and improvement on verbal learning (tested by Rey Auditory Verbal Learning Test) was found only in controls. Education was significantly related to outcome in patients and age was related to outcome in controls. We conclude that neurocognitive function is relatively stable over 4.5 years in patients with long-term treated schizophrenia, in line with previous scientific research. The authors discuss the impact of age and education and limitations of the study.

Kinetics of tyrosine transport and cognitive functioning in schizophrenia

BACKGROUND Tyrosine supplementation in humans has been shown to improve cognitive functioning. Several studies have demonstrated a decreased maximal transport capacity of tyrosine (Vmax) across the cell membrane and an increased affinity (Km) of tyrosine to membrane binding sites in schizophrenic patients. A lack of tyrosine for dopamine synthesis with impairment of dopaminergic transmission could impair cognitive functioning. Aberrant tyrosine kinetics in patients with schizophrenia might therefore be associated with cognitive dysfunction--a core feature of schizophrenia. METHODS Tyrosine kinetics was determined in cultured fibroblasts from 36 schizophrenic patients. The kinetic parameters Vmax and Km were calculated and then the patients were divided into two groups according to the median of the kinetic parameters. A comprehensive neuropsychological test battery was used to evaluate cognitive functioning. RESULTS Patients with low Km (below the median) had poorer cognitive performance than patients with high Km (above the median). Vmax did not discriminate schizophrenic patients with cognitive dysfunction to the same extent. CONCLUSIONS Changes in tyrosine transport probably influence cognitive functioning via the dopamine system. However, our findings of a relation between low Km and cognitive dysfunction may have a more complex background. It is suggested that the connection is related to genetically determined membrane factors that disturb communication/transmission among neurons.

The effects of breast cancer diagnosis and surgery on cognitive functions

Abstract Background. Women with breast cancer (BC) report cognitive impairment. Receiving a BC diagnosis may have a negative psychological impact. We sought to determine whether a diagnosis of BC and subsequent surgical treatment reduced cognitive function. Material and methods. We recruited women, who had a positive radiographic finding, consecutively from the mammography screening program at Stockholm South General Hospital. All subjects completed the Headminder Web-based neuropsychological battery Cognitive Stability Index (CSI) for response speed, processing speed, memory, and attention at enrolment (T1, Baseline). CSI was administered again, after BC was ruled out, or after sector resection or mastectomy, if BC was confirmed by cytology or biopsy (T2, Retest). Results and conclusion. Of the 148 women approached, 146 were enrolled; 69 were healthy and 77 had BC. Comparison between groups at baseline, according to independent t-test, showed significant differences in response speed and processing speed. Cognitive abilities did not decline in either group on any of the measured domains. Our results suggest that a diagnosis of BC and subsequent surgery is not associated with substantial cognitive decline at retest. However, the lack of improvement in attention at retest among BC patients may be suggestive of a decline.

Frontal lobe and basal ganglia metabolism studied with PET in patients with incapacitating obsessive-compulsive disorder undergoing capsulotomy

Regional cerebral metabolic rates of glucose (rCMRgl) were determined with positron emission tomography (PET) in five patients with chronic, treatment-resistant, incapacitating obsessive-compulsive disorder (OCD) undergoing psychosurgery. Preoperative values were compared with rates observed in healthy volunteers examined with the same PET system. Here we report primary data pertaining to the orbital gyri and the caudate nuclei, regions in which disordered metabolism has been observed in OCD. In contrast to previous reports, our patients did not display increased rCMRgl relative to controls, a possible reflection of the particularly malignant forms of OCD which they had. Our findings neither address the issue of the causes of OCD nor preclude that other brain regions may be dysfunctional in that illness

Stability of performance on neuropsychological tests in patients with schizophrenia

Abstract This study evaluated the stability of performance on neuropsychological tests in a group of 14 schizophrenic patients. These patients were first tested as inpatients and later on as outpatients. The patients’ results are also compared with matched normal controls and with standardized norms. The patients’ test results were stable over time and no change in performance was found for the patients as a group, suggesting that these aspects of the patients’ functioning were of a trait quality. The patient group had significantly poorer results on a majority of the tests compared with the controls. The variation of the level of cognitive functioning among the patients, however, was great. In clinical practice today, neuropsychological examinations are often included in the diagnostic procedure, and their results also have impact on treatment planning. However, the possibility to generalize the findings is reduced as a consequence of the low number of patients in the study.

Cognitive, psychosocial, somatic and treatment factors predicting return to work after breast cancer treatment.

BACKGROUND Breast cancer (BC) may affect the ability to work. In this study, we want to identify any associations between cognitive, psychosocial, somatic and treatment factors with time to return to work (RTW) among women treated for BC. METHODS AND PARTICIPANTS At eight (baseline) and 11(follow-up) months after BC diagnosis, women who had received adjuvant treatment for early BC at Stockholm South General Hospital completed the Headminder neuropsychological tests to obtain the Cognitive Stability Index (CSI), the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and its Breast Cancer Module. At both time points, we compared the scores from women who had returned to work with those who had not. We also reviewed the medical certificates of women still on sick leave at 8, 11 and 18 months after diagnosis to determine why they had not returned to work. RESULTS At baseline, 29 of 45 enroled women were working and 15 were not (one dropped out after baseline testing). The 14 women still not working 11 months after BC diagnosis had more advanced BC (OR = 3.64, 95% CI 2.01-7.31), lymph-node involvement (OR = 18.80, 95% CI 5.32-90.69) and Her 2-positive tumours (OR = 10.42,95% CI 2.19-65.32) than did working women. None of the scores for the four cognitive domains changed significantly at follow-up in either group. Comments on the medical certificates generally supported these findings. Independently of any adjuvant cancer therapy, overall quality of life improved and most women did RTW 18 months after BC diagnosis. CONCLUSIONS Chemotherapy is associated with longer periods of sick leave. Cognitive functions do not predict RTW. Independently of any adjuvant therapy, most women eventually RTW in a few months. The ability to predict RTW after BC treatment should help prepare higher-risk patients for delayed RTW and allow earlier interventions to restore their social relations and quality of life.