Bruno Baumann

Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender, and heart rate

The authors undertook this study to determine the effects of age, gender, and heart rate (HR) on the results of cardiac autonomic function tests for measuring heart rate variability (HRV) in a large sample of healthy subjects (n=309). Conventional tests (deep breathing, maximum/minimum 30∶15 ratio), and a standardized 5-minute resting study, including spectral analysis of HR, were used. The main findings included (1) the indices of all tests, except for the ratio of the low- (LF) to high-frequency (HF) spectral power (LF/HF ratio) and HR itself, are inversely related to age in both sexes; (2) the 5-minute spectral bands (except for the LF/HF ratio), the variation coefficient, expiratory-inspiratory ratio during deep breathing, and the maximum/minimum 30∶15 ratio are independent of HR; (3) women up to the age of 55 years have a higher resting HR compared with men; (4) young and middleaged women show a significantly lower LF power and LF/HF ratio compared with age-matched men, whereas no significant gender differences are observed in the absolute HF power. The authors computed age- and gender-dependent normal values for each of the HRV indices studied here and discuss the clinical consequences arising from gender differences in HRV.

Schizophrenia and anteroventral thalamic nucleus: selective decrease of parvalbumin-immunoreactive thalamocortical projection neurons

This study was designed to examine possible anatomical changes of thalamocortical circuits in schizophrenics. Previous immunocytochemical studies have shown that parvalbumin, a calcium-binding protein, occurs in thalamocortical projection neurons, but not in GABAergic interneurons in the anteroventral thalamic nucleus (AN). Using parvalbumin-immunocytochemistry we investigated the densities of thalamocortical projection neurons in the AN of schizophrenic cases (n = 12) and controls (n = 14). The densities of all neurons in the AN were estimated by Nissl-staining. The majority of thalamocortical projection neurons in AN were identified by parvalbumin-immunoreaction. Significantly reduced densities of thalamocortical projection neurons were estimated in the right (P = 0.003) and left AN (P = 0.018) in schizophrenic subjects. The densities of all neurons in right and left AN were also diminished in schizophrenics; however, these decreases did not reach statistical significance. The reductions of parvalbumin-positive thalamocortical projection neurons were not correlated with the length of disease, this finding supporting the neurodevelopmental etiology of structural abnormalities in schizophrenia.

Association between conformational mutations in neuroserpin and onset and severity of dementia

BACKGROUND The aggregation of specific proteins is a common feature of the familial dementias, but whether the formation of neuronal inclusion bodies is a causative or incidental factor in the disease is not known. To clarify this issue, we investigated five families with typical neuroserpin inclusion bodies but with various neurological manifestations. METHODS Five families with neurodegenerative disease and typical neuronal inclusions had biopsy or autopsy material available for further examination. Immunostaining confirmed that the inclusions were formed of neuroserpin aggregates, and the responsible mutations in neuroserpin were identified by sequencing of the neuroserpin gene (SERPINI1) in DNA from blood samples or from extraction of histology specimens. Molecular modelling techniques were used to predict the effect of the gene mutations on three-dimensional protein structure. Brain sections were stained and the topographic distribution of the neuroserpin inclusions plotted. FINDINGS Each of the families was heterozygous for an amino acid substitution that affected the conformational stability of neuroserpin. The least disruptive of these mutations (S49P), as predicted by molecular modelling, resulted in dementia after age 45 years, and presence of neuroserpin inclusions in only a few neurons. By contrast, the most severely disruptive mutation (G392E) resulted, at age 13 years, in progressive myoclonus epilepsy, with many inclusions present in almost all neurons. INTERPRETATION The findings provide evidence that inclusion-body formation is in itself a sufficient cause of neurodegeneration, and that the onset and severity of the disease is associated with the rate and magnitude of neuronal protein aggregation.

Volumes of association thalamic nuclei in schizophrenia: a postmortem study

The major association thalamic nuclei, the mediodorsal nucleus (MD) and the medial pulvinar nucleus (PUM) are regarded as important parts of the circuits among association cortical regions. Association cortical regions of the frontal, parietal and temporal lobes have been repeatedly implicated in the neuropathology of schizophrenia. Thus, the aim of the present postmortem study was to investigate the volumes of association thalamic nuclei in this disease. The volumes of the whole thalamus (THAL), MD and PUM were measured in each hemisphere of brains of 12 patients with schizophrenia and 13 age-matched and gender-matched normal control subjects without neuropsychiatric disorders. Patients with schizophrenia exhibited significant volume reductions in both the MD and the PUM, the reductions being more pronounced in the PUM. The volume of the PUM in the left (-19.7%, P=0.02) and right (-22.1%, P=0.01) hemispheres was significantly reduced in the schizophrenia group. The volume of the MD was reduced in both hemispheres in the schizophrenia group. However, the volume reduction was only significant in the left hemisphere (-9.3%, P=0.03). Patients with schizophrenia also exhibited a decreased volume of the THAL in the left (-16.4%, P=0.003) and right (-15.2%, P=0.006) hemispheres. There were no significant correlations between thalamic volumes and duration of illness or age of the patients. In conclusion, the present data indicate volume reductions of association thalamic nuclei in schizophrenia. These anatomical findings are consistent with the view that schizophrenia may be associated with disturbances of association cortical networks. However, the findings of a substantial volume reduction of the THAL suggest that the volumes of additional thalamic nuclei may be also reduced in schizophrenia.

Regional and cellular distribution of neural visinin-like protein immunoreactivities (VILIP-1 and VILIP-3) in human brain

Neural visinin-like proteins (VILIPs) are members of the neuronal subfamily of intracellular EF-hand calcium sensor proteins termed the NCS family, which are thought to play important roles in cellular signal transduction. While numerous studies suggest a wide but uneven distribution of these proteins in rat and chicken brain, their location in, and possible significance for, the human brain, remains to be established. We used specific polyclonal antisera to map the human brain for VILIP-1 and VILIP-3 immunoreactivities. VILIP-1 was detected in cortical pyramidal cells and interneurons, septal, subthalamic and hippocampal neurons (subfields CA1 and CA4 pyramidal cells and especially hilar interneurons) as well as in cerebellar Golgi, basket, granule, stellate and dentate nucleus neurons. Purkinje cells were free of immunoreaction. VILIP-3 was more restricted in its distribution. It was identified in cerebellar Purkinje cells and a subpopulation of granule neurons. Further, neurons belonging to different nuclei of the brain stem and multiple subcortical nerve cells stained for visinin-like protein 3. A weak immunoreaction appeared in cortical and hippocampal neurons. Intracellularly the immunoreactivity appeared in the perikarya, dendrites and some axons. Sometimes, immunostaining was found in the neuropil. Glia did not express visinin-like proteins. Our findings support, from a neuroanatomical viewpoint, the idea that these calcium sensor proteins may be of relevance for neuronal signalling in the human CNS.

Volume deficits of subcortical nuclei in mood disorders A postmortem study.

AbstractStructural changes in subcortical nuclei may underlie clinical symptoms of mood disorders. The goal was to determine whether macrostructural changes exist in brain areas assumed to be involved in regulation of mood and whether such changes differ between major depressive disorder and bipolar disorder. A case–control design was used to compare volumes of all major subcortical nuclei. Brains of patients with major depressive disorder (n = 9) or bipolar disorder (n = 11) or of individuals without a neuropsychiatric disorder (n = 22) were included. Exclusion criteria were a history of substance abuse or histological signs of neurodegenerative disorders.Volumes of the striato–pallidal nuclei, of the hypothalamus, thalamus, amygdala, hippocampus and basal limbic forebrain were determined in the right and left hemisphere by planimetry of 20 μm whole brain serial paraffin sections. Comparisons between patients with bipolar disorder, major depressive disorder and controls showed a significant (Λ = 0.35, F20,56 = 1.93, P = 0.028) overall difference in volumes of all investigated regions with strong effect sizes ( ƒ > 0.40) contributed by the hypothalamus, external pallidum, putamen and thalamus. As compared to controls, a strong effect size (ƒ > 0.40) was found in the bipolar group for smaller volumes of the hypothalamus, external pallidum, putamen and thalamus,whereas in patients with major depressive disorder a strong effect size was only found for a smaller volume of the external pallidum. In conclusion our data suggest that pathways presumably involved in mood regulation have structural pathology in affective disorders with more pronounced abnormalities in bipolar disorder.

The pathomorphology of schizophrenia and mood disorders: similarities and differences

In this article, post-mortem neurohistological and structural imaging studies of schizophrenia and mood disorders are briefly reviewed. In contrast to the large number of post-mortem studies on schizophrenia published during the last 20 years, very few histological studies of affective disorders are available. After commenting on CT and MRI studies, as well as on neuropathological findings on whole-brain size, cortex, frontal and temporal lobes, limbic system, basal ganglia, thalamus, brain stem, and cortical asymmetry, it is concluded that despite a broad overlap in structural findings in the so-called endogenous psychoses, heteromodal association cortex, limbic system, and structural asymmetry are more affected in schizophrenia, while subtle structural abnormalities in the basal ganglia, especially in the nucleus accumbens and in hypothalamic areas, might play a crucial role in mood disorders.

Neuropsychological Correlates of Major Depression: A Short-term Follow-up

The present study investigated neuropsychological correlates of major depression and their course following treatment. We investigated 41 patients with major depression according to DSM-III-R criteria, who do not fulfil criteria of Alzheimers disease, with a standardised clinical interview, different self- and observer-rating depression scales, and a comprehensive neuropsychological examination, and 27 subjects were reinvestigated 4.5 weeks after the first assessment. We found deficits in all cognitive domains with a predominant decline in tasks of cognitive flexibility and fluency. Patients who respond to antidepressive treatment showed a significant improvement in executive functions at the followup examination. Our data support the hypothesis that cognitive disorders in major depression may be associated with a frontostriatal dysfunction.

Volume and neuron number of the mediodorsal thalamic nucleus in schizophrenia: a replication study.

Previous neuropathological studies on the mediodorsal thalamic nucleus (MD) in schizophrenia have yielded conflicting results. While some studies suggested that patients with schizophrenia have a pronounced reduction of the volume and neuron number in the MD, more recent data have not found anatomical alterations in this thalamic nucleus. However, most studies have considerable methodological shortcomings. In the present study, we investigated the volume, neuron density and neuron number in the left and right MD in patients with schizophrenia (n=20) and normal control subjects without neuropsychiatric disorders (n=18). Patients with schizophrenia showed no significant difference in neuron density and total neuron number in the MD. Compared with the control group, patients with schizophrenia had a smaller MD volume in both hemispheres, a difference that approached significance in the left MD (-7.3%) when the whole brain volume was included as a covariate. No significant main group effect of diagnosis was found for the right MD volume. There were no significant correlations between MD volume, neuron density, total neuron number and the duration of illness or the age of the patients. Taken together, the present results suggest that schizophrenia is associated with a moderate volume reduction in the left mediodorsal thalamic nucleus, while the neuron density and the total neuron number are unchanged.

The ventral lateral posterior nucleus of the thalamus in schizophrenia: a post-mortem study

The ventral lateral posterior thalamic nucleus (VLp) is an integral part of both the cerebello-thalamocortical and the basal ganglia-thalamocortical circuit. Although both circuits are thought to be involved in the pathophysiology of schizophrenia, the VLp has not yet been examined in schizophrenia. Using stereological techniques in the brains of eight patients with schizophrenia and in eight age- and sex-matched controls, we measured the nuclear volume of the VLp and obtained estimates of the total number of neurons in this nucleus. Whole brain volume did not differ between the schizophrenia group and the control group and was not correlated to the volume of the right VLp or left VLp. The volume (minus sign25%) and the total neuron number (minus sign27%) of the left VLp were significantly reduced in the schizophrenia group. There were no significant differences in the nuclear volume, neuron density and total neuron number in the right VLp between the schizophrenia group and the control group. There were no significant correlations between length of illness and the nuclear volume, neuron density and total neuron number of the left and right VLp. The present results suggest that the total neuron number of the left VLp is reduced in the schizophrenia group, which may reflect disturbed cerebello-thalamocortical and basal ganglia-thalamocortical circuits in this disease.