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Biomedical subjects

Sabine Landau

Publications and source records attributed to Sabine Landau.

34 records · Page 2Linked to original sources

Early psychological intervention for auditory hallucinations: an exploratory study of young people's voices groups.

Twenty to fifty percent of people with a diagnosis of schizophrenia continue to hear voices despite taking neuroleptic medication. Trials of group cognitive behavioral therapy for adults with auditory hallucinations have shown promising results. Auditory hallucinations may be most amenable to psychological intervention during a 3-year critical period after symptom onset. This study evaluates the effectiveness of group cognitive behavioral therapy (CBT) for young people with recent-onset auditory hallucinations (N = 22), using a waiting list control. Outcome measures were administered at four separate time points. Significant reductions in auditory hallucinations occurred over the total treatment phase, but not over the waiting period. Further investigations in the form of randomized controlled trials are warranted.

Adolescent↗

Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia.

BACKGROUND: The orbitofrontal cortex is involved in the monitoring of reward and in judgement. Lesion studies and functional neuroimaging investigations implicate this region in affective disorders, and altered neuronal and glial cell composition have been observed in this region in subjects with major depressive disorder (MDD). AIMS: Stereologically based investigation of caudal orbitofrontal cortex (cOFC), in 60 postmortem brains from four groups of 14 subjects each with bipolar disorder (BPD), schizophrenia and MDD. METHODS: Glial cell and neuronal size and density were examined in all subjects using stereological probes such as the nucleator and the optical disector. RESULTS: We found statistical evidence for a neuronal size reduction in BPD in layer 1 (21%, p=0.007) and a trend for a reduction in layer 5 (20%, p=0.05). There was a significant interaction effect of brain hemisphere and group on neuronal size in layer 3 (p=0.001), with evidence for reduced layer 3 neuronal sizes in MDD (30%, p<0.001). We found no evidence for group differences in glial cell size nor for differences in glial or neuronal density. CONCLUSIONS: These findings provide preliminary evidence that neuronal size reduction in cOFC is a component of the pathology of BPD. Overall, the data implicate this cortical region in affective disorders, but provide no evidence for neuronal or glial pathology in this region in schizophrenia.

Adult↗

Is impaired set-shifting an endophenotype of anorexia nervosa?

OBJECTIVE: Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recovery; therefore, they may be endophenotypic traits. The goals of this study were to investigate whether set-shifting difficulties are familial by examining discordant sister-pairs in comparison with healthy unrelated women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychological performance. METHOD: Forty-seven pairs of sisters discordant for anorexia nervosa and 47 healthy unrelated women who were comparable in age and IQ completed neuropsychological tasks selected to assess set-shifting ability. Analyses of variance with standard errors that are robust against correlations within family clusters were used to compare the groups. Results were adjusted for obsessive-compulsive, anxiety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects. RESULTS: Sisters with and without anorexia nervosa took significantly longer than unrelated healthy women to shift their cognitive set (CatBat task) and demonstrated greater perceptual rigidity (Haptic Illusion task) but did not differ significantly from each other. Women with anorexia nervosa were slower than other groups on Trail Making tasks. Women who had fully recovered from anorexia nervosa made significantly fewer errors than those with acute anorexia nervosa on the Trail Making alphabet task, but these subgroups did not differ on other measures. CONCLUSIONS: Both affected and unaffected sisters had more set-shifting difficulties than unrelated healthy women. This finding, together with the replicated finding that set-shifting difficulties persist after recovery, suggests that set-shifting difficulties are trait characteristics and may inform the search for the endophenotype in anorexia nervosa.

Adult↗

Clustering of suicides among people with mental illness.

BACKGROUND: Most previous investigations of imitative suicide have reported suicide clustering in the general population, either temporal clustering following media reporting of suicide or case studies of geographically localised clusters. AIMS: To determine whether space - time and space-time-method clustering occur in a national case register of those who had recent contact with mental health services and had died by suicide and to estimate the suicide imitation rate in this population. METHOD: Knox tests were used for space-time and space-time-method clustering. Model simulations were used to estimate effect size. RESULTS: Highly significant space-time and space-time-method clustering was found in a sample of 2741 people who died by suicide over 4 years who had had recent contact with one of 105 mental health trusts. Model simulations with an imitation rate of 10.1% (CI 4-17) reproduced the observed space-time-method clustering. CONCLUSIONS: This study provides indirect evidence that imitative suicide occurs among people with mental illnesses and may account for about 10% of suicides by current and recent patients.

Cause of Death↗

Suppression of human immunodeficiency virus replication in human brain tissue by nucleoside reverse transcriptase inhibitors.

Human immunodeficiency virus (HIV) infection of the brain is associated pathologically with neuronal damage and loss. Clinically cognitive impairments can develop, which in some can be improved by highly active antiretroviral therapy (HAART), whereas in others, the infection persists despite treatment. The efficacy of antiretrovirals to treat cognitive impairments may be related to their ability to suppress viral replication in the brain and also to prevent neurodegeneration. To investigate this question, the authors assessed the ability of stavudine (300 nM), zidovudine (2 nM), and abacavir (300 nM) to suppress viral replication in human brain tissue aggregates infected with HIV-1 SF162. Aggregates were cultured for 4 weeks and exposed to nucleoside reverse transcriptase inhibitors (NRTIs) either 24 h prior, simultaneously, or 24 h post infection. Viral replication was assessed by p24 enzyme-linked immunosorbent assay (ELISA) in culture medium. The authors observed a statistically significant reduction in the rate of viral replication for stavudine added 24 h prior to infection univariate analysis of variance ([UANOVA], t = 2.55, df = 17, P =.021). Decreased viral replication observed with zidovudine and abacavir was not statistically significant.

AIDS Dementia Complex↗

Cell density and cortical thickness in Heschl's gyrus in schizophrenia, major depression and bipolar disorder.

There is evidence that the superior temporal gyrus and Heschl's gyrus within it are implicated in schizophrenia. We investigated neuronal and glial cell density and cortical thickness within Heschl's gyrus, using the optical disector to estimate cell density within cortical layers 3 and 5 in tissue derived postmortem from people with diagnoses of major depressive disorder, schizophrenia and bipolar disorder, compared with normal controls (n=15 per group). No significant difference in neuronal or glial cell density or in cortical thickness was observed between the groups; our findings therefore provide no support for the presence of cellular pathology within Heschl's gyrus in schizophrenia.

Auditory Cortex↗

Two-dimensional assessment of cytoarchitecture in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia: evidence for decreased neuronal somal size and increased neuronal density.

BACKGROUND: Abnormalities of cortical neuronal organization and reductions in neuronal somal size have been reported in schizophrenia. The purpose of this investigation was to assess patterns of neuronal and glial distribution in the anterior cingulate cortex (ACC) in major depressive disorder (MDD), schizophrenia, bipolar disorder (BPD), and normal control subjects (15 subjects per group). METHODS: Estimates for neuronal somal and glial nuclear size and density were obtained. We employed two-dimensional morphometric analysis to examine the location of neurons and glia in a 1000-microm-wide strip of cortex. RESULTS: A decreased clustering of neurons was seen in BPD (p =.001). No other group differences were observed in the clustering of neurons, glia, or of neurons about glia. Neuronal somal size was reduced in layer 5 in schizophrenia (18%, p =.001), BPD (16%, p <.001), and MDD (9%, p =.01). Neuronal density was increased in layer 6 in BPD (63%, p =.004) and schizophrenia (61%, p =.006) and in layer 5 in MDD (24%, p =.018) and schizophrenia (33%, p =.003). CONCLUSIONS: The results of this study indicate that reduced neuronal somal size and increased neuronal density in cortical layers 5 and 6 of the ACC may be key features of schizophrenia, MDD, and BPD.

Adult↗

The Maudsley Bipolar Disorder Project: the effect of medication, family history, and duration of illness on IQ and memory in bipolar I disorder.

BACKGROUND: Despite the growing recognition of the importance of cognitive impairment in psychiatric disorders, the effect of clinical factors, such as medication use and family history of affective disorders, on cognition in bipolar I disorder patients still remains unclear. This study examines the contribution of known and potential predictors to both general intellectual function and memory in a representative population of bipolar I disorder patients. METHOD: Of the 425 patients receiving treatment within a defined catchment area, 63 were identified as having bipolar I disorder. Of these patients, 43 were enrolled in the study and participated in a personal interview by a psychiatrist. All patients were invited to participate in a personal interview by a psychiatrist, and information on family history, past psychiatric history, past and current treatments, duration of illness, and age at onset was collected, in addition to demographic data. Cognitive performance was assessed using the Wechsler Adult Intelligence Scale-Revised, the National Adult Reading Test, and the Wechsler Memory Test III. RESULTS: Forty-three patients with DSM-IV bipolar I disorder were enrolled into the Maudsley Bipolar Disorder Project. Patients on treatment with antipsychotic drugs had a lower current full scale IQ, lower general memory scores, and lower working memory scores. A family history of affective disorders was associated with a higher full scale IQ, but not with either general or working memory measures. Duration of illness was negatively associated with general memory scores, but had no effect on either IQ or working memory measures. CONCLUSION: Current antipsychotic medication, duration of illness, and family history of affective disorder were the most significant predictors of IQ and memory function in bipolar I disorder patients.

Adult↗

The density and spatial distribution of GABAergic neurons, labelled using calcium binding proteins, in the anterior cingulate cortex in major depressive disorder, bipolar disorder, and schizophrenia.

BACKGROUND: There is strong evidence for the presence of a deficit in cortical gamma aminobutyric acid (GABA) neurotransmission in schizophrenia. In this investigation we have used the calcium binding proteins (CBPs) parvalbumin (PV), calretinin (CR), and calbindin-D28K (CB) as markers of these neuronal populations, and have characterized their pattern and density in schizophrenia, bipolar disorder (BPD), and major depressive disorder (MDD). METHODS: We examined the anterior cingulate cortex (ACC) in four groups of 15 brains each from subjects with schizophrenia, MDD, and BPD, and from control subjects. Using immunocytochemistry to identify these distinct neuronal populations, we quantified their areal density and spatial pattern organization. RESULTS: There were reductions in the density of CB-labeled neurons in layer 2 in schizophrenia (34%; p =.04) and BPD (33%; p =.05) compared with control subjects; however, after correction for multiple comparisons these findings no longer attained formal statistical significance. We observed no differences in the density of the neuronal populations labeled by CR or PV in any layer of the cortex in any disorder compared with control subjects. There was increased clustering among PV-labeled neurons in BPD compared with control subjects but no significant differences in the spatial organization of the other neuronal subpopulations in any disorder. CONCLUSIONS: The study provides some support for the presence of a deficit in GABAergic neurons in schizophrenia and shows that these changes are not specific to schizophrenia. The findings indicate that there may be a pathophysiological condition, shared by subjects with schizophrenia and BPD, which operates to selectively reduce the number or protein expression of CB-immunoreactive neurons.

Adult↗

Reproducibility of quantitative dynamic MRI of normal human tissues.

The aim of the study was to establish the normal range and to evaluate the reproducibility of dynamic contrast enhanced MRI (DCE-MRI) parameter estimates in normal human pelvic tissues. Nineteen patients with prostate cancer, undergoing androgen deprivation treatment, had paired DCE-MRI examinations of the pelvis using spoiled gradient-echo sequences. Quantitative enhancement parameters were calculated for each examination: transfer constant (K(trans)), leakage space (v(e)) and maximum contrast medium accumulation (MCMA) of pelvic muscles, bone marrow and fat. Descriptive and reproducibility statistics were calculated: within-patient standard deviation (wSD), repeatability and within-patient coefficient of variation (wCV). The femoral head and ischiorectal fat showed large numbers of non-enhancing pixels (81 and 88%, respectively). The ischial bone marrow had the highest values of kinetic parameter estimates (K(trans) 0.554 min(-1), v(e) 18.5% and MCMA 0.164 mmol/kg). Muscle parameters values were lower (K(trans) 0.126-0.137 min(-1), v(e) 10.6-11.5% and MCMA 0.077-0.086 mmol/kg). The mean difference between paired examinations was not significantly different from zero for any parameter. v(e) and MCMA had the lowest wCV (between 19 and 29%). For individuals, a log(10) K(trans) change of approximately 0.90 in muscles and 0.52 in the ischium would be statistically significant. The corresponding absolute changes for v(e) are 6.7% in muscle and 13.6% in the ischium. For a group of 19 patients, small changes are statistically significant (muscle log(10) K(trans) 0.208 and v(e) 1.5% and ischium log(10) K(trans) 0.123 and v(e) 3.1%). Fat and the femoral head are unreliable tissues from which to obtain kinetic parameter estimates due to poor enhancement. v(e) and MCMA have smaller coefficient of variation than K(trans) in muscles and ischium. Reproducibility studies of normal and pathological tissues should be incorporated into clinical research protocols that measure treatment effects by DCE-MRI techniques.

Adipose Tissue↗

Observations on haematological and cardiovascular effects of erythropoietin treatment in multiple system atrophy with sympathetic failure.

Symptomatic autonomic neuropathy and in particular sympathetic failure mediated postural hypotension often accompanies Multiple System Atrophy (MSA). Release of erythropietin is under sympathetic control and we and others have previously reported that severe autonomic failure may be associated with a normocytic normochromic anaemia and erythopietin (EPO) deficiency. In this paper we describe the haematological, cardiovascular and clinical observations on a patient with MSA and severe symptomatic autonomic neuropathy who had haematological and clinical improvement (substantial increase in standing blood pressure) following subcutaneous EPO treatment.

Aged↗

Serum prolactin levels in Parkinson's disease and multiple system atrophy.

The hypothalamic-pituitary axis (HPA) may be involved early in multiple system atrophy (MSA), whereas in idiopathic Parkinson's disease (IPD) its impairment seems to be correlated with motor disability. The release of prolactin (PRL) is mediated through the HPA and an increase in PRL levels is documented during stress. In this study, we investigated basal and erect PRL levels to assess whether basal PRL or changes in PRL levels after 60 degrees head-up tilt (HUT; orthostatic stress) could distinguish between MSA and IPD patients. We studied five patients with MSA on levodopa treatment, five levodopa-naive MSA patients, nine IPD patients on dopaminergic treatment, six drug-naive IPD patients and six normal individuals. PRL levels were measured in the supine position after 30 minutes rest and during 60 degrees HUT after 5 and 15 minutes. Baseline PRL values were significantly lower for patients with IPD than for those with MSA, both for levodopa-treated and naive patients ( p < 0.004, estimated decrease 55.1 %, 95 % CI from 29.4 % to 71.52 %). After orthostatic stress PRL levels were increased in healthy individuals after 15 minutes of HUT ( p = 0.044, estimated increase 11.5 %, 95 % CI from 0.4 % to 23.8 %), whereas there was no evidence for a change of PRL levels in patients with MSA or IPD after 5 and 15 minutes of HUT. We also did not find any evidence for a difference in PRL change after HUT between MSA and IPD patients. Baseline PRL levels might differentiate between early MSA and IPD, being higher in MSA. However, orthostatic stress using HUT appears unable to differentiate between MSA and IPD.

Aged↗

Vasoconstrictor response to topical beclomethasone in major depression.

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been frequently described in depression. Due to the closed-loop nature of the HPA axis, one possible cause of this overactivity may be a defect in negative feedback regulation, in particular an abnormality of the glucocorticoid receptor (GR). In the present study, the vasoconstrictor response to the topical glucocorticoid, beclomethasone, was used to examine GR function in depression. Topical beclomethasone was applied in four concentrations (10 microl each of 3, 10, 30 and 100 microg/ml) to the forearms of 22 subjects with major depression and their age- and sex-matched controls. Skin blanching responses were compared between the depressed and control groups and, within the depressed group, on the basis of the modified dexamethasone suppression test (DST), between cortisol suppressors and non-suppressors. Depressed subjects demonstrated a significantly reduced vasoconstrictor response compared to controls (P=0.0001). No difference was detected between cortisol suppressors and non-suppressors in their skin blanching responses. These findings suggest that peripheral GR function is abnormal in depression but that the reduced vasoconstrictor response to beclomethasone is not necessarily a secondary effect of hypercortisolaemia or HPA axis overactivity.

Administration, Topical↗

Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder.

Reductions in glial cell density and neuronal size have been described recently in major depressive disorder (MDD). Considering the important trophic influence of glia on neurons, we hypothesized that this glial cell deficit is more prominent close to neurons. In this investigation we have characterized neuronal and glia cytoarchitecture in prefrontal area 9 using spatial point pattern techniques and two-dimensional measures of cell size and density. In post-mortem brain tissue of subjects with MDD, schizophrenia, bipolar disorder (BPD), and normal controls (15 subjects per group), we examined the laminar location and size of all neurons and glial nuclei in a 500 microm wide strip of cortex extending from the pia to the grey-white matter border. In MDD, we observed reductions in glial cell density (30%; P = 0.007) in layer 5 and neuronal size (20%; P = 0.003) in layer 6. We also found that glial cell density (34%; P = 0.003) was reduced in layer 5 in schizophrenia, while neuronal size was reduced in layers 5 (14%) (P = 0.006) and 6 (18%; P = 0.007) in BPD. The spatial pattern investigation of neurons and glia demonstrated no alteration in the clustering of glia about neurons between control and patient groups. These findings confirm that glial cell loss and neuronal size reductions occur in the deeper cortical layers in MDD, but provide no support for the hypothesis that an altered spatial distribution of glia about neurons plays a role in the development of these changes.

Analysis of Variance↗

[Interferon-alpha-induced psychiatric side effects in patients with chronic viral hepatitis: a prospective, observational, controlled study].

AIMS: Patients with chronic viral hepatitis suffer from a high prevalence of psychiatric problems. Furthermore, the treatment for chronic viral hepatitis, with interferon (IFN) alpha, induces the occurrence of further psychopathological symptoms. The authors examined whether patients with a pre-existing psychiatric diagnosis had more severe IFN alpha-induced psychiatric adverse effects, and whether they were more likely to interrupt the IFN alpha therapy, compared with control patients with no pre-existing psychiatric diagnosis. They also examined the psychopharmacological management of the interferon-alpha-induced psychiatric side effects. METHODS: The authors studied prospectively 60 patients with chronic hepatitis B or C in Cagliari, Italy. Patients underwent psychiatric assessment before starting interferon alpha and monthly throughout the therapy. RESULTS: After adjusting for the baseline psychopathology, there was no statistically significant difference in interferon-alpha-induced psychiatric adverse effects between patients with a pre-existing psychiatric diagnosis and controls. There was also no evidence that psychiatric cases were more likely than controls to interrupt the IFN alpha therapy because of psychiatric side effects. Moreover, there was no difference in the psychiatric adverse effects severe enough to require psychopharmacological treatment. Finally, psychopharmacological management successfully treated psychiatric symptoms induced by the IFN alpha. CONCLUSIONS: Patients with a pre-existing psychiatric diagnosis do not have a specific vulnerability to interferon-alpha-induced psychiatric adverse effects.

Adolescent↗