Johannes Schröder

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia.

Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (χ2 = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder.

Motor dysfunction and sensorimotor cortex activation changes in schizophrenia: A study with functional magnetic resonance imaging.

Recent studies demonstrate a diminished activation of the sensorimotor cortex and supplementary motor area (SMA) in schizophrenia which may be involved in the pathogenesis of neurological soft signs (NSS). Yet, the question whether a retarded motor performance may account for these changes remained to be clarified. Twelve DSM-III-R schizophrenics and 12 healthy controls were included. All subjects were right-handed. Nine patients received clozapine, two conventional neuroleptics, and one was drug-free. Functional magnetic resonance imaging (fMRI) was obtained in a resting condition and during pronation/supination at three speed levels (low, medium, and high) with motor performance recorded simultaneously using a pronation/supination device. While measures of motor retardation (i.e., repetition rate and amplitude of the movements) did not differ between patients and controls, the variability of performance was significantly (P < 0.05) increased in the patients group. In addition, patients with schizophrenia showed a significantly (P < 0.05) decreased activation of the sensorimotor cortices. Similar, although nonsignificant (P = 0.09) activation changes were observed in the SMA. Activation differences were more pronounced at a slow speed and in the drug-free patient. These results confirm a diminished sensorimotor cortex and SMA activation and indicate that variability of performance rather than retarded performance per se may correspond to these changes.

Prevalence of mild cognitive impairment in an elderly community sample

The term mild cognitive impairment refers to cognitive deficits which exceed normal physiological aging processes, but do not fulfill the criteria for dementia. While recent studies indicate that the respective deficits can be reliably assessed, different diagnostic criteria have prevented a wide application of this diagnosis in clinical practice. The aims of the present study were (1) to assess the prevalence rates of four current diagnostic concepts and (2) to investigate mild cognitive impairment with respect to psychological and sociodemographic variables. Data from 202 probands recruited from the interdisciplinary longitudinal study on adult development were analyzed. On the time of examination, probands were between 60 to 64 years old and in a good health. The following prevalence rates were determined: 13.5% for age-associated memory impairment (AAMI), 6.5% for age-consistent memory impairment (ACMI), 1.5% for late-life forgetfulness (LLF), and 23.5% for aging-associated cognitive decline (AACD). Complaints of cognitive deficits were significantly correlated with higher scores on depression and neuroticism scales but with none of the neuropsychological measures. Reduced performance in neuropsychological tests was associated with a lower educational level and socioeconomic status. We conclude that the prevalence rates of mild cognitive impairment are highly dependent on the diagnostic criteria applied. In this respect the self-report of cognitive decline might be a less useful criteria. Longitudinal studies are warranted to further elucidate the predictive value of these diagnostic criteria.

Reduced olfactory bulb and tract volume in early Alzheimer's disease—A MRI study

Olfactory dysfunction has been reported to occur already in the early stages of Alzheimers disease (AD) and to increase with disease severity. In neuropathological research, the deposition of neurofibrillary tangles and neuritic plaques in the olfactory bulb and tract (OBT) of AD patients has been consistently demonstrated. We used high-resolution magnetic resonance imaging (MRI) to determine the volume of the OBT in 21 patients with early AD and in 21 healthy comparison subjects. The OBT was manually traced on consecutive coronal slices. When compared to healthy controls, right, left and mean OBT volumes were significantly reduced in patients with AD (p<0.01). In AD patients, the mean OBT volume was significantly correlated with global cognitive performance as determined by the mini-mental state examination (r=0.605; p=0.004). Manual tracing on MRI images revealed OBT atrophy to be present early in the course of AD. Since the respective findings were associated with cognitive impairment, they may contribute to early recognition and diagnosis of the disease.

Structural and functional correlates of subsyndromes in chronic schizophrenia.

Recent psychopathological studies consistently identified a delusional, a negative, and a disorganized subsyndrome in chronic schizophrenia. The aim of our studies was to investigate the subsyndromes with respect to their underlying cerebral changes using computed tomography (CT) and positron emission tomography (PET). In a CT study 50 DSM III schizophrenics were subgrouped according to four factors identified by a factor analysis of BPRS ratings. This procedure identified three chronic clusters (delusional ideation, negative symptoms, and disorganization) and one cluster with a remitting course of the disorder. Both the negative and the delusional subsyndrome were associated with a widening of the frontal interhemispheric fissure. Disorganization was associated with neurological soft signs, an increased ventricle brain ratio, and width of the 3rd ventricle. The same subgrouping was applied in a 18F-deoxyglucose PET study of 79 neuroleptic free DSM III schizophrenic patients and 47 healthy controls. The delusional subsyndrome was associated with a decreased hippocampal function, while the negative subsyndrome showed a prominent hypofrontality and left temporal cortex changes. Both the delusional and the negative subsyndrome were associated with a decreased activity in the medial frontal gyrus in comparison to the other schizophrenic patients and the healthy controls. The disorganized subsyndrome was characterized by an overactivity in the parietal cortex and motor strip and a decreased activity in the corpus callosum. These findings support the differentiation of three subsyndromes in chronic schizophrenia. The subsyndromes seem to be characterized by deviant patterns of cerebral alterations, rather than deficits in a single location.

Syntactic comprehension deficits in Alzheimer's disease.

Syntactic comprehension of German patients with dementia of the Alzheimer type was investigated and compared to healthy controls matched with respect to age, sex, and education. Special attention was directed at syntactic structures, which, in contrast to a language like English, are feasible in a grammatically rich language like German. In a sentence picture matching paradigm, only semantically reversible sentences were used. Syntactic complexity ranged from simple active voice sentences to more complex sentences like center-embedded object relative sentences. In comparison to their controls, patients showed a deficit in nearly all categories. Their performance was not influenced by age, but was heavily influenced by the degree of cognitive impairment. Patients with mild cognitive impairment, as defined by a MMSE score of 20 or higher, showed only slight difficulties in syntactic processing, whereas patients with moderate to severe impairment (MMSE < 20) did not perform above chance limits in most syntactic categories. It appears as though syntactic comprehension is only mildly affected in the early stages of Alzheimers disease and is rather severely impaired in more advanced stages. In the present report, results are discussed in terms of working memory demands for syntactic processing.

Clock drawing performance and brain morphology in mild cognitive impairment and Alzheimer’s disease

The Clock Drawing Test (CDT) is a widely used instrument in the neuropsychological assessment of Alzheimers disease (AD). As CDT performance necessitates several cognitive functions (e.g., visuospatial and constructional abilities, executive functioning), an interaction of multiple brain regions is likely. Fifty-one subjects with mild cognitive impairment, 23 with AD and 15 healthy controls underwent high-resolution magnetic resonance imaging. Optimized voxel-based morphometry (VBM) was performed to investigate the putative association between CDT performance and gray matter (GM) density throughout the entire brain. In the first step of analysis (p<.001, uncorrected), VBM revealed a reduced GM density in numerous cortical (temporal lobe, frontal lobe, parietal lobe, cerebellum) and subcortical (thalamus, basal ganglia) brain regions to be associated with poorer CDT performance. When corrected for multiple comparisons (p<.01), the associations remained significant predominantly in the left temporal and--less pronounced--the right temporal lobe. VBM demonstrated CDT performance to depend on the integrity of widely distributed cortical and subcortical areas in both brain hemispheres with accentuation in the left-sided temporal lobe region.

Patterns of cortical activity and memory performance in Alzheimer's disease

BACKGROUNDnDeclarative memory changes are the hallmark of Alzheimers disease, although their functional neuroanatomy is not restricted to a single structure. Factor analysis provides statistical methods for evaluating patterns of cerebral changes in regional glucose uptake.nnnMETHODSnThirty-three Alzheimers patients and 33 age- and gender-matched control subjects were studied with magnetic resonance imaging and positron emission tomography with [(18)F] deoxyglucose. During the tracer-uptake period, subjects performed a serial verbal learning task. Cortical activity was measured in 32 regions of interest, four in each lobe on both hemispheres.nnnRESULTSnFactor analysis with varimax rotation identified seven factors explaining 80% of the variance (parietal cortex, occipital cortex, right temporo-prefrontal areas, frontal cortex, motor strip, left temporal cortex, and posterior temporal cortex). Relative to control subjects, Alzheimers patients showed significantly reduced values on the factors occipital cortex, right temporo-prefrontal areas, frontal cortex, and left temporal cortex. The factor temporo-prefrontal areas showed large differences between patients with good and poor performance, but little difference when control subjects were similarly divided.nnnCONCLUSIONSnFindings suggest that Alzheimers disease is characterized by altered patterns of cortical activity, rather than deficits in a single location, and emphasize the importance of right temporo-prefrontal circuitry for understanding memory deficits.

Subsyndrome der chronischen Schizophrenie

In zahlreichen psychopathologischen Studien werden drei Subsyndrome der chronischen Schizophrenie unterschieden: das wahnhafte Subsyndrom ist durch ein persistierendes wahnhaft-halluzinatorisches Erleben, das asthenische durch eine ausgepragte Negativsymptomatik und das desorganisierte Subsyndrom durch formale Denkstorungen mit Antriebssteigerung charakterisiert. Diese Subsyndrome wurden im Hinblick auf neuropsychologische Defizite sowie morphologische und funktionelle cerebrale Veranderungen untersucht. Demnach ist das wahnhafte Subsyndrom mit Storungen des deklarativen Gedachtnisses und einer herabgesetzten Aktivierung im Temporallappen assoziiert. Fur das asthenische Subsyndrom sind Defizite im Bereich des prozeduralen Gedachtnisses und eine herabgesetzte frontale Aktivitat („Hypofrontalitat“) charakteristisch. Beim desorganisierten Subsyndrom bestehen Storungen des Arbeitsgedachtnisses, diskrete motorische und sensorische Storungen sowie eine veranderte Aktivierung im sensomotorischen Kortex. Eine durchgehende “typologische„ Trennung zwischen den einzelnen Subsyndromen ist anhand der beschriebenen neuropsychologischen Defizite und funktionellen cerebralen Storungen jedoch kaum moglich. Die Subsyndrome sind demnach weniger als Subtypen schizophrener Psychosen denn als psychopathologische Dimensionen anzusehen, die sich in der individuellen Symptomatik uberschneiden.