A Disappearing Heritage: The Clinical Core of Schizophrenia

This article traces the fundamental descriptive features of schizophrenia described in the European continental literature form Kraepelin and Bleuler, culminating with the creation of the International Classification of Diseases (ICD)-8 (1974). There was a consensus among the researchers that the specificity and typicality of schizophrenia was anchored to its “fundamental” clinical core (with trait status) and not to positive psychotic features, which were considered as “state”, “accessory” phenomena. The clinical core of schizophrenia was, in a diluted form, constitutive of the spectrum conditions (“schizoidia” and “latent schizophrenia”). The fundamental features are manifest across all domains of consciousness: subjective experience, expression, cognition, affectivity, behavior, and willing. Yet, the specificity of the core was only graspable at a more comprehensive Gestalt-level, variously designated (eg, discordance, autism, “Spaltung”), and not on the level of single features. In other words, the phenomenological specificity was seen as being expressive of a fundamental structural or formal change of the patient’s mentality (consciousness, subjectivity). This overall change transpires through the single symptoms and signs, lending them a characteristic phenomenological pattern. This concept of schizophrenia bears little resemblance to the current operational definitions. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and ICD-10 seem to diagnose a subset of patients with chronic paranoid-hallucinatory variant of schizophrenia

Looking at the Schizophrenia Spectrum Through the Prism of Self-disorders: An Empirical Study

Nonpsychotic anomalies of subjective experience were emphasized in both classic literature and phenomenological psychiatry as essential clinical features of schizophrenia. However, only in recent years, their topicality with respect to the construct validity of the concept of the schizophrenia spectrum has been explicitly acknowledged, mainly as a consequence of the increasing focus on early detection and prevention of psychosis. The current study tested the hypothesis of a specific aggregation of self-disorders (SDs, various anomalies of self-awareness) in schizophrenia-spectrum conditions, comparing different diagnostic groups; 305 subjects, previously assessed in the Copenhagen Schizophrenia Linkage Study, were grouped into 4 experimental samples, according to their Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) main diagnosis: schizophrenia, (n = 29), schizotypal personality disorder (n = 61), other mental illness not belonging to the schizophrenia spectrum (n = 112), and no mental illness (n = 103). The effect of diagnostic grouping on the level of SDs was explored via general linear model and logistic regression. The diagnosis of schizophrenia and schizotypy predicted higher levels of SDs, and SDs scores were significantly different between spectrum and nonspectrum samples; the likelihood of experiencing SDs increased as well with the diagnostic severity. The findings support the assumption that SDs are a discriminant psychopathological feature of the schizophrenia spectrum and suggest their incorporation to strengthen its construct validity, with potential benefit for both early detection and pathogenetic research

Flow behavior in liquid molding

The liquid molding (LM) process for manufacturing polymer composites with structural properties has the potential to significantly lower fabrication costs and increase production rates. LM includes both resin transfer molding and structural reaction injection molding. To achieve this potential, however, the underlying science base must be improved to facilitate effective process optimization and implementation of on-line process control. The National Institute of Standards and Technology (NIST) has a major program in LM that includes materials characterization, process simulation models, on-line process monitoring and control, and the fabrication of test specimens. The results of this program are applied to real parts through cooperative projects with industry. The key feature in the effort is a comprehensive and integrated approach to the processing science aspects of LM. This paper briefly outlines the NIST program and uses several examples to illustrate the work

The Silent Side of the Spectrum: Schizotypy and the Schizotaxic Self

The identification of individuals carrying unexpressed genetic liability to schizophrenia is crucial for both etiological research and clinical risk stratification. Subclinical psychopathological features detectable in the nonpsychotic part of the schizophrenia spectrum could improve the delineation of informative vulnerability phenotypes. Inspired by Meehl's schizotaxia-schizotypy heuristic model, we tested anomalous subjective experiences (self-disorders, SDs) as a candidate vulnerability phenotype in a sample of nonpsychotic, genetically high-risk subjects. A total of 218 unaffected members of 6 extended multiplex families (assessed between 1989 and 1999 during the Copenhagen Schizophrenia Linkage Study) were stratified into 4 groups of increasing psychopathological expressivity: no mental illness (NMI), no mental illness with schizotypal traits (NMI-ST), personality disorders not fulfilling other personality disorders (OPDs), and schizotypal personality disorder (SPD). We tested the distribution of SDs among the subgroups, the effect of SDs on the risk of belonging to the different subgroups, and the effect of experimental grouping and concomitant psychopathology (ie, negative symptoms (NSs) and subpsychotic formal thought disorder [FTD]) on the chances of experiencing SDs. SDs distribution followed an incremental pattern from NMI to SPD. SDs were associated with a markedly increased risk of NMI-ST, OPDs, or SPD. The odds of SDs increased as a function of the diagnostic category assignment, independently of sociodemographics and concomitant subclinical psychopathology (NSs and FTD). The results support SDs as an expression of schizotaxic vulnerability and indicate a multidimensional model of schizotypy—characterized by SDs, NSs, FTD—as a promising heuristic construct to address liability phenotypes in genetically high-risk studies

Exploring The Ligand Binding Site On The Dopamine Transporter By Photoaffinity Labeling And Site-Directed Mutagenesis

The dopamine transporter (DAT) is a neuronal presynaptic transmembrane protein that clears released dopamine (DA) from the synaptic space, regulating the neurotransmitter concentration and availability, DAT and the related serotonin (SERT) and norepinephrine (NET) transporters belong to the SLC6 family of Na+ and CI- dependent symporters, and are major targets for the action of several drugs, including the psychostimulant cocaine. DAT is predicted to possess 12 transmembrane spanning domains (TMs), with both N- and C-termini located intracellularly. Extensive research efforts to gain insight on the molecular aspects of DAT have been attempted, but the three-dimensional arrangement of the protein as well as the molecular mechanisms involved in substrate translocation remain undiscovered. Cocaine and other structurally diverse compounds bind to DAT with high affinity and inhibit its transport activity, but their binding site within the protein and the mechanism by which they block DA transport remain unclear. Two distinct ligand interaction sites at transmembrane domains (TMs) 1-2 and 4-6 have been identified using irreversible uptake-blockers. The current studies explore the incorporation site of the novel cocaine analogue [125I]MFZ-2-24, which is structurally similar to the previously characterized [125 I]RTI 82, but the reactive azido (N3) group is differentially positioned within the cocaine pharmacophore. Trypsin and cyanogen bromide (CNBr) proteolytic maps of [125I]MFZ-2-24 labeled rat and human DATs, followed by epitope-specific immunoprecipitation were used to localize the incorporation site of the ligand to a 13 amino acid stretch in TM1, between residues I67 and L80. This highly conserved region harbors the functionally essential D79 and residues involved in substrate and inhibitor binding. In marked contrast, incorporation of [125I]RTI 82 occurs in TM6, demonstrating that differential positioning of the N 3 group on the cocaine pharmacophore leads to distinct incorporation patterns. This further indicates that TMs 1 and 6 are in dose proximity three dimensionally and participate in the reversible binding of cocaine to DAT