In recent years, there has been much focus on the apparent heterogeneity of schizophrenic symptoms. By contrast, this article proposes a unifying account emphasizing basic abnormalities of consciousness that underlie and also antecede a disparate assortment of signs and symptoms. Schizophrenia, we argue, is fundamentally a self-disorder or ipseity disturbance (ipse is Latin for "self" or "itself") that is characterized by complementary distortions of the act of awareness: hyperreflexivity and diminished self-affection. Hyperreflexivity refers to forms of exaggerated self-consciousness in which aspects of oneself are experienced as akin to external objects. Diminished self-affection or self-presence refers to a weakened sense of existing as a vital and self-coinciding source of awareness and action. This article integrates recent psychiatric research and European phenomenological psychiatry with some current work in cognitive science and phenomenological philosophy. After introducing the phenomenological approach along with a theoretical account of normal consciousness and self-awareness, we turn to a variety of schizophrenic syndromes. We examine positive, then negative, and finally disorganization symptoms-attempting in each case to illuminate shared distortions of consciousness and the sense of self. We conclude by discussing the possible relevance of this approach for identifying early schizophrenic symptoms.

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Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across approximately 40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show Fst values that are among the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high Fst values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone.

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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.

The usefulness of current psychiatric classification, which is based on ICD/DSM categorical diagnoses, remains questionable. A promising alternative has been put forward as the "transdiagnostic" approach. This is expected to cut across existing categorical diagnoses and go beyond them, to improve the way we classify and treat mental disorders. This systematic review explores whether self-defining transdiagnostic research meets such high expectations. A multi-step Web of Science literature search was performed according to an a priori protocol, to identify all studies that used the word "transdiagnostic" in their title, up to May 5, 2018. Empirical variables which indexed core characteristics were extracted, complemented by a bibliometric and conceptual analysis. A total of 111 studies were included. Most studies were investigating interventions, followed by cognition and psychological processes, and neuroscientific topics. Their samples ranged from 15 to 91,199 (median 148) participants, with a mean age from 10 to more than 60 (median 33) years. There were several methodological inconsistencies relating to the definition of the gold standard (DSM/ICD diagnoses), of the outcome measures and of the transdiagnostic approach. The quality of the studies was generally low and only a few findings were externally replicated. The majority of studies tested transdiagnostic features cutting across different diagnoses, and only a few tested new classification systems beyond the existing diagnoses. About one fifth of the studies were not transdiagnostic at all, because they investigated symptoms and not disorders, a single disorder, or because there was no diagnostic information. The bibliometric analysis revealed that transdiagnostic research largely restricted its focus to anxiety and depressive disorders. The conceptual analysis showed that transdiagnostic research is grounded more on rediscoveries than on true innovations, and that it is affected by some conceptual biases. To date, transdiagnostic approaches have not delivered a credible paradigm shift that can impact classification and clinical care. Practical "TRANSD"iagnostic recommendations are proposed here to guide future research in this field.

Oxidative stress could be involved in the pathophysiology of schizophrenia, a major psychiatric disorder. Glutathione (GSH), a redox regulator, is decreased in patients' cerebrospinal fluid and prefrontal cortex. The gene of the key GSH-synthesizing enzyme, glutamate cysteine ligase modifier (GCLM) subunit, is strongly associated with schizophrenia in two case-control studies and in one family study. GCLM gene expression is decreased in patients' fibroblasts. Thus, GSH metabolism dysfunction is proposed as one of the vulnerability factors for schizophrenia.