Ralf Hemmingsen

Basal ganglia volumes in drug-naive first-episode schizophrenia patients before and after short-term treatment with either a typical or an atypical antipsychotic drug

The present study examined basal ganglia volumes in drug-naive first-episode schizophrenic patients before and after treatment with either a specific typical or atypical antipsychotic compound. Sixteen antipsychotic drug-naive and three minimally medicated first-episode schizophrenic patients and 19 matched controls participated. Patients were randomly assigned to treatment with either low doses of the typical antipsychotic drug, zuclopenthixol, or the atypical compound, risperidone. High-resolution magnetic resonance imaging (MRI) scans were obtained in patients before and after 12 weeks of exposure to medication and in controls at baseline. Caudate nucleus, nucleus accumbens, and putamen volumes were measured. Compared with controls, absolute volumes of interest (VOIs) were smaller in patients at baseline and increased after treatment. However, with controls for age, gender and whole brain or intracranial volume, the only significant difference between patients and controls was a Hemisphere x Group interaction for the caudate nucleus at baseline, with controls having larger left than right caudate nuclei and patients having marginally larger right than left caudate volumes. Within patients, the two medication groups did not differ significantly with respect to volume changes after 3 months of low dose treatment in any of the VOIs. Nevertheless, when medication groups were examined separately, a significant volume increase in the putamen was evidenced in the risperidone group. The altered asymmetry in caudate volume in patients suggests intrinsic basal ganglia pathology in schizophrenia, most likely of neurodevelopmental origin.

Neurological abnormalities in schizophrenic patients: a prospective follow-up study 5 years after first admission.

Madsen AL, Vorstrup S, Rubin P, Larsen JK, Hemmingsen R. Neurological abnormalities in schizophrenic patients: a prospective follow‐up study 5 years after first admission. Acta Psychiatr Scand 1999: 100: 119–125.

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

SUMMARY 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.

Frontal Dopamine D2/3 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.

A longitudinal study of prisoners on remand: psychiatric prevalence, incidence and psychopathology in solitary vs.non‐solitary confinement

Objective: To compare two levels of stress (solitary confinement (SC) and non‐SC) among remand prisoners as to incidence of psychiatric disorders in relation to prevalent disorders.

Validation of a digital video tracking system for recording pig locomotor behaviour.

We are introducing a system for automatically tracking pig locomotor behaviour. Transposing methods for the video-based tracking of rodent behaviour engenders several problems. We have therefore improved existing methods, based on image-subtraction, to offer increased flexibility and accuracy in tracking large-sized animals in situations with a constantly changing background. The improved tracking algorithms introduce a reference frame, which does not include the animal and is automatically updated, and implementation of an automatic threshold detection algorithm. This makes the system more robust to the tracking environment, which could even be of the same colour as the animal, and allows the tracking environment to change during recording. We validated the system by estimating the repeatability, accuracy, and basic noise level, and tested the system in different levels of animal activity evoked by administration of apomorphine (APO) to minipigs in an open field test. Seven pigs each received the vehicle and three doses of APO (0.05, 0.1, and 0.3 mg/kg i.m.), and the locomotor behaviour of each session was recorded for 60-min. The calculated coefficient of repeatability was 0.6%, indicating high repeatability and the basic noise level of the tracking system was estimated to be 2%. Administration of the two lowest doses of APO was accompanied by increased locomotor activity of the pigs. Thus, this digital video-based tracking system for automatically tracking the spontaneous locomotor behaviour of pigs is highly reliable and accurate, and was able to detect well-known effects of APO in pig locomotor activity.

Progressive atrophy of the frontal lobes in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment

This prospective study examined the interaction of clinical course of disease and brain structure with time in schizophrenic patients.

Cognitive deficits and levels of IQ in adolescent onset schizophrenia and other psychotic disorders

Cognitive deficits have been found to be prevalent in early onset schizophrenia. Whether these deficits also characterise other early onset psychotic disorders to a similar degree is unclear, as very few comparative studies have been done. The primary purpose of this study was to compare the profile and severity of cognitive impairments in first-episode early onset psychotic patients who received the schizophrenia diagnosis to those diagnosed with other non-organic, non-affective psychotic disorders. The secondary purpose was to examine whether the profile of cognitive deficits, in terms of intelligence, executive functions, memory, attention and processing speed was global or specific. First-episode psychotic adolescents (N = 39) between the ages 11 and 17 years were included, 18 of whom were diagnosed with schizophrenia, and 21 with other non-organic, non-affective psychoses, using ICD-10 criteria. A healthy control group (N = 40) was included, matched on gender and age. Cognitive functions were assessed using WISC-III/R, the CANTAB battery, WCST, Trail Making B, fluency tasks, and Buschkes selective reminding task. A similar profile and level of impairment was found on measures of attention, executive functions, reaction time, and memory in the schizophrenic and psychotic adolescent groups. However, analyses of WISC-III factor profiles suggested that early onset schizophrenia patients may have more global IQ deficits than non-organic, non-affective psychoses when examined recently after illness onset. Compared to the deficits of adult schizophrenia described in the literature, the results suggest relatively spared simple reaction times in early onset patients.

Regional cerebral blood flow in patients with transient ischemic attacks studied by Xenon-133 inhalation and emission tomography.

Cerebral blood flow CBF was studied in 14 patients with transient ischemic attacks TIA and arteriosclerotic neck vessel disease. CBF was measured by a rapidly rotating single photon emission computerized tomograph using Xenon-133 inhalation. This method yields images of 3 brain slices depicting CBF with a spatial resolution of 1.7 cm. Based primarily on the clinical evidence and on the angiographical findings embolism was considered the pathogenetic factor in 10 cases, whereas chronic hemodynamic insufficiency rendered symptomatic by postural factors probably accounted for the symptoms in 4 patients. Of the 14 patients, all studied days to weeks after the most recent TIA, four showed hypoperfused areas on the CBF-tomograms and with roughly the same location hypodense areas on CT-scanning, i.e. areas of complete infarction. However, an additional five patients showed reduction of CBF in areas with no abnormality on the CT-scan. The abnormal blood flow pattern was found to be unchanged after clinically successful reconstructive vascular surgery. This suggests the presence of irreversible ischemic tissue damage without gross emollition (incomplete infarction). It is concluded, that TIAs are often harmful events, as no less than 9 of the 14 patients studied had evidence of complete and/or incomplete infarction. Thorough examination and rational therapy should be instituted as soon as possible to prevent further ischemic lesions.

Neurological abnormalities in patients with schizophrenia or schizophreniform disorder at first admission to hospital : correlations with computerized tomography and regional cerebral blood flow findings

Forty‐five patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time had a neurological examination, including integrative sensory and complex motor acts, by a trained neurologist. The patients were studied by CT (computerized tomography) and rCBF (regional cerebral blood flow) as well. A control group of 24 healthy volunteers was included. The patients had significantly more neurological abnormalities (NA) than the healthy volunteers. Medication did not explain the discrepancy. The NA were associated with sulcal enlargement and smaller brains as visualized by CT but not with ventricular enlargement. There was no association between the regional flow values and NA.