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Ralf Hemmingsen

Publications and source records attributed to Ralf Hemmingsen.

At least 19 recordsLinked to original sources
PubMed2006

The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture.

In an attempt to delineate the prefrontal cortex (PFC) in the Göttingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers were visualized using standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an MRI paramagnetic tracer. The in vivo tract tracing turned out to be very sensitive with a high correspondence to the histological labelling. Tracers injected into the mediodorsal thalamus labelled the medial and rostral pole of the frontal lobe as well as the anterior cingulate, anterior insular and dorsomedial frontal cortices. Subsequently, the reciprocity and specificity of these connections were tested from injections into the traced frontal cortices indicating that the PFC has cortical connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Göttingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed that the Göttingen minipig PFC constitutes about 24% of the total neocortex volume and 10% of the total brain volume.

Animals↗
PubMed2006

Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender.

BACKGROUND: The aim of the study was to examine extrastriatal dopamine D(2/3) receptor binding and psychopathology in schizophrenic patients, and to relate binding potential (BP) values to psychopathology. METHODS: Twenty-five drug-naive schizophrenic patients and 20 healthy controls were examined with single-photon emission computerized tomography (SPECT) using the D(2/3)-receptor ligand [123I]epidepride. RESULTS: In the hitherto largest study on extrastriatal D(2/3) receptors we detected a significant correlation between frontal D(2/3) BP values and positive schizophrenic symptoms in the larger group of male schizophrenic patients, higher frontal BP values in male (n = 17) compared to female (n = 8) patients, and - in accordance with this - significantly fewer positive schizophrenic symptoms in the female patients. No significant differences in BP values were observed between patients and controls; the patients, however, had significantly higher BP in the right compared to the left thalamus, whereas no significant hemispheric imbalances were observed in the healthy subjects. CONCLUSIONS: The present data are the first to confirm a significant correlation between frontal D(2/3) receptor BP values and positive symptoms in male schizophrenic patients. They are in agreement with the hypothesis that frontal D(2/3) receptor activity is significant for positive psychotic symptoms. Additionally, the data support a thalamic hemispheric imbalance in schizophrenia.

Adult↗
PubMed2006

No significant association of the 5' end of neuregulin 1 and schizophrenia in a large Danish sample.

Neuregulin 1 has been implicated as a susceptibility gene in schizophrenia. Several research groups have reported association with the 5' end of the gene although no causative variant has been reported. We have investigated whether there is association with the 5' end of the gene in Danish schizophrenia patients. We found that the at-risk haplotype initially reported in the Icelandic population was not found in significant excess (or = 1.4, p = 0.12). The haplotype structure in the Danish sample was similar to that of other reported in other Caucasian populations and highly different from that of Chinese.

Case-Control Studies↗
PubMed2006

The postnatal development of cerebellar Purkinje cells in the Göttingen minipig estimated with a new stereological sampling technique--the vertical bar fractionator.

The postnatal development of total number and perikaryon volume of cerebellar Purkinje cells was estimated in the Göttingen minipig cerebellar cortex using a new stereological approach, the vertical bar fractionator. Data were obtained from the brains of five neonate and five adult female Göttingen minipigs. The total number of Purkinje cells ranged from 1.83 x 10(6) in the neonate to 2.82 x 10(6) in the adult Göttingen minipig. The number-weighted mean perikaryon volume of Purkinje cells increased concurrently from around 6,800 microm(3) in the neonate to 17,600 microm(3) in the adult. The study demonstrates that a pronounced postnatal neurogenesis in Purkinje cell number and perikaryon volume is part of the growth and development of the cerebellum in the Göttingen minipig. The Purkinje cells of the Göttingen minipig were found to be substantially large compared with human and represents the largest cells described hitherto from mammalian cerebella. The vertical fractionator is a new sampling technique, which allows the combination of a fractionator design on vertical bar sections excluding exhaustive sampling and bias from artificial edges. By design, the sections are perfect stereological vertical sections and provide the basis for unbiased estimates of total number of structural entities in the brain, including surface area, fibre length and particle volume.

Animals↗
PubMed2006

Association between the CCR5 32-bp deletion allele and late onset of schizophrenia.

OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission to a psychiatric hospital department served as a measure of disease onset. RESULTS: Patients and comparison subjects differed marginally in their genotype distribution, with a slightly higher frequency of the deletion allele seen in the patients. The authors found the deletion allele to be associated with higher age at first admission. After age at first admission was analyzed as a continuous variable, it was dichotomized using 40 years as the cutoff. With this approach the authors found that genotype distributions of patients with age at first admission above the cutoff (possible cases of late-onset schizophrenia) and healthy subjects differed significantly. This was reflected in an increased frequency of the deletion allele in the patient subgroup. Patients with ages at first admission below and above 40 years significantly differed in distribution of genotypes and alleles, with an overrepresentation of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without affecting the disease susceptibility.

Adolescent↗
PubMed2006

The postnatal development of neocortical neurons and glial cells in the Göttingen minipig and the domestic pig brain.

The first mathematically unbiased estimates of neocortical cell numbers are presented from the developing pig brain, including a full description of tissue processing and optimal sampling for application of the stereological optical fractionator method in this species. The postnatal development of neocortical neurons and glial cells from the experimental Göttingen minipig was compared with the postnatal development of neocortical neurons in the domestic pig. A significant postnatal development was observed in the Göttingen minipig brain for both neuronal (28%; P=0.01) and glial cells (87%; P<0.01). A corresponding postnatal development of neurons was not detected in the domestic pig brain. The reason for this strain difference is not known. The mean total number of neocortical neurons is 324 million in the adult Göttingen minipig compared with 432 million in the domestic pig. The glial-to-neuron cell ratio is around 2.2 in the adult Göttingen minipig. Based on these results, the domestic pig seems to be a more suitable model for evaluating the effects of developmental insults on human brain growth and neuronal development than the Göttingen minipig.

Animals↗
PubMed2005

Assessment of in vivo MR imaging compared to physical sections in vitro--a quantitative study of brain volumes using stereology.

The object of the present study was to compare stereological estimates of brain volumes obtained in vivo by magnetic resonance imaging (MRI) to corresponding volumes from physical sections in vitro. Brains of ten domestic pigs were imaged using a 3-T scanner. The volumes of different brain compartments were obtained from MR images by two observers and from physical sections using the Cavalieri estimator in combination with point counting. Paired t tests revealed no significant differences between the two methods for any of the five compartments considered, except for the basal gray compartment. However, although intraobserver difference of MRI estimates was acceptable, the interobserver difference was not. A statistical highly significant difference of 11-41% was observed between observers for volume estimates of all compartments considered. The study demonstrates that quantitative MRI is susceptible to observer dependent interpretation of images.

Algorithms↗
PubMed2005

Acquisition of visually guided conditional associative tasks in Göttingen minipigs.

Fourteen Göttingen minipigs were trained on two different visually guided conditional associative tasks. In a spatial conditional task, a black stimulus signalled that a response to the left was correct, and a white stimulus signalled that a response to the right was correct. In a conditional go/no-go task, a blue stimulus signalled go, and a red stimulus signalled no-go. The pigs were trained until a behavioural criterion of 90% correct for each of two consecutive sessions. For the spatial conditional task, all pigs reached this criterion in 520 trials or less. For the conditional go/no-go task, all pigs, except three, reached this criterion in 1600 trials or less. Sows and boars learned equally fast. The tasks can be useful for the testing of cognitive function in pig models of human brain disorders.

Animals↗
PubMed2005

Integrated treatment of first-episode psychosis: effect of treatment on family burden: OPUS trial.

BACKGROUND: The families of patients with first-episode psychosis often play a major role in care and often experience lack of support. AIMS: To determine the effect of integrated treatment v. standard treatment on subjective burden of illness, expressed emotion (EE), knowledge of illness and satisfaction with treatment in key relatives of patients with a first episode of schizophrenia-spectrum disorder. METHOD: Patients with ICD-10 schizophrenia-spectrum disorders (first episode) were randomly assigned to integrated treatment or to standard treatment. Integrated treatment consisted of assertive community treatment, psychoeducational multi-family groups and social skills training. Key relatives were assessed with the Social Behaviour Assessment Schedule (SBAS, burden of illness), the 5-min speech sample (EE), and a multiple choice questionnaire at entry and after 1 year. RESULTS: Relatives in integrated treatment felt less burdened and were significantly more satisfied with treatment than relatives in standard treatment. There were no significant effects of intervention groups on knowledge of illness and EE. CONCLUSIONS: The integrated treatment reduced family burden of illness and improved satisfaction with treatment.

Adaptation, Psychological↗
PubMed2004

Discriminations, reversals, and extra-dimensional shifts in the Göttingen minipig.

Göttingen minipigs were trained on a set-shifting procedure involving discriminations, reversals, and extra-dimensional shifts. The discriminations used were black-white discriminations and right-left discriminations. The initial visual and spatial discrimination seemed equally difficult, and only for the visual modality was reversal found to be more difficult than the initial discrimination. Visual reversal was more difficult than spatial reversal, and a larger number of perseverative sessions were found for visual reversal compared to spatial reversal. The acquisition of the extra-dimensional shift from the visual to the spatial dimension was not inferior to the learning of spatial reversal. Neither was the acquisition of the extra-dimensional shift from the spatial to the visual dimension inferior to the learning of visual reversal. Thus, no evidence was found for attention to stimulus dimensions in discrimination learning of the pigs.

Animals↗
PubMed2004

Prepulse inhibition in patients with Alzheimer's disease.

Prepulse inhibition (PPI) is used as a measure for sensorimotor gating. Studies in animals have indicated that hippocampus and entorhinal cortex, structures which are affected in mild Alzheimer's disease (AD), are involved in the regulation of PPI. The objectives of this study were to determine if patients with very mild AD had altered PPI, and to study possible correlations between PPI and cognitive performance or neuropsychiatric symptoms. A passive acoustic PPI paradigm was applied in 48 patients with either mild AD or Mild Cognitive Impairment (MCI) and in 49 healthy controls. No differences were found between patients and healthy controls regarding PPI. Further, PPI was not found to correlate with cognitive performance or neuropsychiatric symptoms. PPI is significantly altered in patients with neuropsychiatric disorders associated with dopaminergic, glutamatergic and/or serotonergic dysfunctions, such as schizophrenia. Since mild AD is primarily associated with loss of cholinergic markers in the limbic regions this study suggests that acetylcholine only plays a minor role in the regulation of PPI.

Acetylcholine↗
PubMed2003

Psychiatric morbidity in a neurology-based memory clinic: the effect of systematic psychiatric evaluation.

OBJECTIVES: To estimate the prevalence of psychiatric morbidity and the effect of systematic psychiatric evaluation in patients referred to a memory clinic in a neurological setting. DESIGN: Descriptive case-series study in consecutive referrals to a memory clinic. SETTING: An outpatient multidisciplinary memory clinic in a neurological setting. PARTICIPANTS: An index group of 100 consecutive patients (aged 60-89) referred for diagnostic evaluation of cognitive symptoms during a period of 8 months and a reference group of 686 consecutive patients (aged 60-98) referred during a previous period of 54 months. In the index group, a systematic psychiatric evaluation was performed in addition to the neurological evaluation and routine investigations. In the reference group, patients had the same basic evaluation, but psychiatric evaluation was optional and was performed in 21% of the patients. MEASUREMENTS: Prevalence of primary psychiatric morbidity in the index and reference groups according to international clinical criteria and multidisciplinary consensus report and three key psychiatric symptoms: delusions, hallucinations, and affective symptoms in the index group. RESULTS: Twenty-three percent of patients in the index group had a primary psychiatric disease. A primary psychiatric disease was diagnosed in 8% of patients in the reference group (P<.001). One or more psychiatric symptoms were identified in 72% of all patients in the index group. CONCLUSION: Psychiatric conditions and symptoms are frequent in elderly patients with cognitive symptoms, including those referred to a neurological memory clinic. The data provide evidence for a multispecialty and multidisciplinary approach to the diagnosis and management of patients with possible dementia.

Aged↗
PubMed2002

Psychiatric emergency outreach: a report on the first 2 years of functioning in Copenhagen.

The purpose of the study was to evaluate psychiatric emergency outreach after functioning for a period of 2 years in Copenhagen, Denmark. Psychiatric emergency outreach was staffed by a psychiatrist and an ambulance driver, and the target group was defined as mentally ill and persons in severe crisis. For each of 935 calls covering 777 different patients, a registration form with social and clinically relevant data was filled out. After the 2-year period, patients were looked up in the National Cause of Death Register and the National Psychiatric Case Register. A total of 66% were previously registered as psychiatric patients, and in 37% of all calls, the patient had psychotic symptoms. In 25% of the calls, the patient was admitted to psychiatric hospital; 38% of the admissions were involuntary. Forty-eight per cent of the calls were initiated by relatives, friends or neighbours. Suicidal behaviour was frequent. There were significantly more calls in socially deprived areas. Standard Mortality Rates were high for all causes of death (5.00), and especially for suicide (31.98). In conclusion, psychiatric emergency outreach seems to fulfil some of its purpose.

Adolescent↗
PubMed2002

Spontaneous object recognition in the Göttingen minipig.

Göttingen minipigs were tested in an object recognition procedure based on spontaneous exploration. Eight pigs were exposed to two similar objects in a sample trial and after a one-hour delay exposed to two objects, one familiar and one novel, in a test trial. The pigs explored the novel object significantly more than the familiar object in the test trial (p<0.05), thereby showing recognition of the familiar object. Furthermore, habituation of exploration of the familiar object between the sample trial and the test trial was found (p<0.05). The procedure can be useful for testing of spontaneous trial-unique memory in pigs.

Animals↗