A new five factor model of schizophrenia

Schizophrenic psychopathology is heterogeneous and multidimensional. Various strategies have been developed over the past several years to assess and measure more accurately discrete domains of psychopathology. One of the more fruitful strategies to investigate more homogenous domains of psychopathology has been the positive-negative syndrome approach. However, this approach is unable to address a number of important issues. Most schizophrenics present a mixed syndrome; the criteria for what constitutes a positive and negative syndrome are variable; distinguishing primary from secondary negative symptoms can be difficult. In order to address some of these problems, we propose the introduction of a five syndrome model based on a reanalysis of factor analytic procedures used on 240 schizophrenics assessed with the Positive and Negative Syndrome Scale (PANSS). We present data on a 5-factor solution which appears to best fit the psychopathological data and which is supported by three independent and comparable factor analyses; negative, positive, excitement, cognitive and depression/anxiety domains of psychopathology give patients their individual mark. Data on internal consistency of the five factors and on initial validation using demographic and clinical variables are presented.     

Synaptogenesis in the Prefrontal Cortex of Rhesus Monkeys

Since the turn of the century, the prefrontal association areasof the cerebral cortex have been thought to be among the lastregions of the cortical mantle to develop. We have examinedthe course of synaptogenesis in the macaque prefrontal cortexby quantitative electron microscopic analysis in 25 rhesus monkeysranging in age from embryonic day 47 (E47) to 20 years of age.A series of overlapping electron micrographs spanning the wholecortical thickness in each animal provided data on the number,the proportion, and the density of synapses per unit area (N_A)and per unit volume (N_V) of neuropil. The tempo and kinetics of synapse formation in prefrontal cortexclosely resemble those described for sensory and motor areas,particularly during the stages of synapse acquisition and overproduction(Rakic et al., 1986). In young embryos, we describe a precorticalphase (E47-E78), when synapses are found only above and below,but not within, the cortical plate. Following that, there isan early cortical phase, from E78 to E104, during which synapsesaccumulate within the cortical plate, initially exclusivelyon dendritic shafts. The next rapid phase of synaptogenesisbegins at 2 months before birth and ends approximately at 2months after birth, culminating with a mean density of 750 millionsynapses per cubic micrometer. This accumulation is largelyaccounted for by a selective increase in axospine synapses inthe supragranular layers. The period of explosive synaptic densityis followed by a protracted plateau stage that lasts from 2months to 3 years of age when synaptic density remains relativelyconstant. The final period of decline, from 3 years throughover 20 years of age, is marked by a slight but statisticallysignificant decline in synaptic density. Concurrent recruitment of synapses with that of sensory andmotor areas supports the concept that the initial establishmentof cortical circuitry is governed by general mechanisms commonto all areas, independent of their specific functional domain.The finding that synaptic density is relatively stable fromearly adolescence through puberty (the plateau period) is indicativeof the importance, in primates, of a consistent and high synapticdensity during the formative years when learning experiencesare most intense.     

Regional Distribution of Neurofibrillary Tangles and Senile Plaques in the Cerebral Cortex of Elderly Patients: A Quantitative Evaluation of a One-Year Autopsy Population from a Geriatric Hospital

Detailed analyses of the neuropathologic changes in the cerebralcortex of elderly individuals and Alzheimer's disease patientshave demonstrated that certain components of the neocorticaland hippocampal circuits are likely to be selectively vulnerable.Based on the distribution of neurofibrillary tangles (NFTs)and senile plaques, it has been proposed that a global cortico-corticaldisconnection leads to the loss of integrated functions observedin Alzheimer's disease. In order to investigate the distributionof lesions associated with aging as well as with the earliestsymptoms of senile dementia, we performed a quantitative neuropathologicavaluation of a large series of elderly patients representingthe entire autopsy population for the year 1989 from a geriatrichospital. Among the 145 cases quantitatively assessed, therewere 102 nondemented patients, 33 patients presenting clinicallywith globally intact intellectual function but early signs ofimpairment of specific cognitive functions, and 10 cases withsenile dementia of the Alzheimer type. All of the cases hadNFTs in layer II of the entorhinal cortex, regardless of theirclinical diagnosis, and most cases had some NFTs in the CA1field of the hippocampus. Severe pathologic changes within theinferior temporal neocortex were observed only in the dementedcases. The extent of amyloid deposition was not correlated withthe clinical diagnosis and seemed to be present in the neocorticalareas earlier than in the hippocampal formation. Also, severalcases contained NFTs without amyloid deposition, but amyloidnever occurred without NFTs. These results suggests that involvementof certain structures within the hippocampal formation is aconsistent feature of aging. Thus, involvement of the hippocampalformation may be a necessary, but not sufficient, conditionfor the clinical expression of dementia, which is likely tobe more closely related to the progressive degeneration of selectneuronal populations in the neocortex.     

The use of telescoping guide catheters for coronary sinus cannulation and sub-selecting tributaries in left ventricular lead placement

Introduction Failure to enter the coronary sinus (CS) with a guiding catheter and entering its tributaries remains challenging in left ventricle (LV) pacing lead implants for cardiac resynchronization therapy (CRT). A dual telescoping catheter system (8F outer/6F inner) is designed to provide the ability to adjust the catheter curve size, shape and/or reach to the patients’ anatomy avoiding the need for catheter change. Methods Five different designs for CS cannulation were randomly tested in 64 patients scheduled for CRT device implant. Results In 33 consecutive patients three adaptable telescoping guiding catheter systems were tested per patient, the adaptable catheters had higher overall cannulation success rates (68, 63 and 62%) compared to the fixed shape catheter (46%) and an greater cannulation success rate when the CS location was not known (70, 53 and 72% vs 33% for the fixed shape). In a second group of 31 CRT patients the two telescoping catheters had similar high levels of success (71–80%), with or without using the inner catheter. Conclusions The telescopic system is adaptable to a wide range of anatomical variations in patients and can result in a higher CS cannulation success rate due to its adjustability in the RA in search for the CS ostium. On top of this the inner catheter allows for sub-selecting the CS tributaries.     

Salivary gland malignancy with divergent differentiation: is it a teratocarcinosarcoma?

Four poorly differentiated malignant lesions occurred in a 60-year-old Chinese male in the nasal cavity, submandibular gland, a lymph node in the neck, and the mandible. These malignant lesions developed within an 8-year period and each showed distinctive histological features. Among these malignant lesions, the neoplasm in the submandibular gland presented variegated histological and immunohistochemical (IHC) features and posed a diagnostic challenge in interpretation. Based on microscopic and IHC findings, we believe the diagnosis of teratocarcinosarcoma is justified for the submandibular neoplasm and the metastasis in the lymph node. The pathological features and diagnoses of these malignant lesions are discussed.     

Ultrasound for the assessment of the embolic risk of carotid plaques

In a prospective study we compared duplex-ultrasound characteristics of symptomatic internal carotid artery (ICA) stenoses with cranial computerized tomographic (CCT) findings in 82 patients suffering from completed or transient middle cerebral artery symptoms. The aim was to assess the pathogenic role of ICA plaque morphology and the potential embolic risk of ICA plaques. The degree of carotid stenosis was estimated by spectral analysis of the pulsed Doppler signal. The CCT findings were classified as being either normal, lacunar lesions, hemodynamically induced low-perfusion infarctions, or territorial embolic infarctions. According to their ultrasonic features we characterized the ICA plaque surface as smooth or irregular and their structure as homogeneous or heterogeneous. Plaques with an irregular surface and heterogeneous echogenicity dominated significantly in CCT-territorial infarctions (p < 0.01), whereas hemodynamically induced low-perfusion infarctions showed no relationship with any plaque characteristic. High degree ICA stenoses (> 50>%) dominated in both territorial infarctions and low-perfusion infarctions, as compared to ipsilateral normal CCT or lacunes (p < 0.05). Normal CCT and lacunar infarctions were associated with homogeneous and smooth plaques (both p < 0.05). We conclude that > 50% ICA stenoses can cause both hemodynamically induced low-perfusion infarctions as well as thromboembolic territorial infarctions, whereas ulcerated and heterogeneous plaques constitute a high risk factor for arterio-arterial embolic stroke. Furthermore, carotid ultrasound may help to estimate the clinical significance of carotid lesions.     

Patients with heart attacks are not valid models for medial temporal lobe amnesia. A neuropsychological and FDG-PET study with consequences for memory research

Equating the condition after cardiac arrest with that of medial temporal damage, and consequently medial temporal lobe amnesia, is questioned on the basis of results from a patient who was studied neuropsychologically as well as with static and dynamic imaging methods (MRI, PET) 6–9 months after a heart attack. The patient manifested severe and persistent anterograde and retrograde amnesia, as well as further cognitive deteriorations. While MRI only indicated non-specific cortical atrophy, PET revealed a severe bilateral affection of the thalamus and of both medial and lateral temporal cortices as well as occipito-parietal hypometabolism. The neuropsychological status indicates that patients with a diagnosis of cardiac arrest may suffer very severe and persistent cognitive deficits; the imaging analyses show that cardiac arrests may lead to quite severe and widespread brain damage which, however, may not be visible with current magnetic resonance imaging technology, but which is clearly apparent from positron emission tomography. These data suggest that patients with a condition after a heart attack may not be valid models for pure hippocampal—or even medial temporal lobe—pathology, as they may suffer much more widespread brain damage.     

Regional preferences of AMPA receptor modulators determined through agonist binding autoradiography

Autoradiographic techniques were used to test if positive modulators of AMPA-type glutamate receptors have regionally differentiated effects on ligand binding. Cyclothiazide, a drug with ten fold greater effects on `flip' than `flop' splice variants of the receptors, had unequal effects across the subdivisions of hippocampus; i.e., it reduced [³H]AMPA binding in field CA3 with an EC₅₀ of 24 μM and in field CA1 and dentate gyrus with EC₅₀s between 60 and 100 μM. The EC₅₀ for the drug's influence on binding was also significantly lower in the superficial than in the deeper layers of the neocortex, though these differences were not as pronounced as those in the hippocampus. The ampakine CX614, a compound with a modest preference for flop variants, had a slightly lower EC₅₀ for its effects on [³H]AMPA binding in CA1 than in CA3. This result was confirmed with [³H]fluorowillardiine binding. The effects of the ampakine in neocortex tended to be greater in the deeper than superficial layers but this did not reach statistical significance. These results indicate that differential effects of modulators on AMPA receptor subunits are reflected in their relative potency across brain subdivisions. This raises the possibility that subclasses of positive modulators will exhibit a measurable degree of selectivity in their physiological and behavioral influences.