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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is probable that all schizophrenics have abnormalities in the medial temporal lobe, which differ in degree but not in kind. The structures of the medial temporal lobe are believed to have a crucial role in the integration and processing of the output from the association cortex. Dysfunction of this system could result in the clinical symptoms that form the core of the schizophrenia syndrome. The structural differences appear to fit the profile of a disturbance in the normal pattern of brain development. The asymmetrical patterns of normal brain development explain how such a disturbance simultaneously affecting both hemispheres could, disproportionately, affect the left (dominant) hemisphere. Epidemiological and pathological evidence points to aberrant genetic mechanisms as being the cause of the developmental anomaly in the majority of cases; environmental factors probably play a minor role. Despite the great progress made in solving the enigma of the structural changes in the brains of schizophrenics, the cause(s) of the changes--the aberrant genetic mechanism controlling brain development--may prove difficult to define.
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PMID:Schizophrenia: a neuropathological perspective. 201 55

The biological enigma of schizophrenia has led, on the basis of thin evidence, to widen the field of clinical research to a study of endomorphines in this disease. Too many different methods of measuring the levels of opiate peptides in the CSF have been used so that it is not possible to analyse the results statistically. Clinical trials of agonists and antagonists to the opiate receptors have once again emphasised the biochemical heterogeneity of schizophrenics but have not allowed any confirmation that the endorphinical system plays any part in the genesis or symptomatology of schizophrenia. The presence of sub-groups who respond positively to experimental treatment can lead to the hope, despite the uncertainties of their mode of pharmacological action, to the next advance in the routine treatment of schizophrenia.
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PMID:[Endomorphines in schizophrenia]. 303 7

The development of the schizophrenogenic mother concept within American psychiatry has been something of an enigma. This interpersonal hypothesis of the etiology of schizophrenia involved a sharp break in the historical progression of understanding the disease. Though former promulgators have gone from calling the schizophrenogenic mother a "half truth" to a psychiatric "myth," this psychiatric concept remains a puzzle, still (Arieti 1997, p. 353; Neill 1990). The circumstances surrounding the development, flowering, and decline of the schizophrenogenic mother concept have not been fully explored.
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PMID:The schizophrenogenic mother concept in American psychiatry. 891 46

Hallucinations in schizophrenia represent an important clinical problem, an interesting neuropsychological enigma, and a significant challenge for neuroscientific research. Functional neuroimaging techniques allow the in vivo, systems-level study of brain dysfunction underlying this debilitating symptom. Clinical and scientific vantage points that can inform the design and interpretation of functional neuroimaging studies of schizophrenic hallucinations are outlined. These include considerations of the phenomenology of hallucinations, the relationship of hallucinations to other symptoms of schizophrenia, and the neuropsychological functions that are thought to be disrupted in hallucinations. They also include the anatomical and chemical brain systems in which abnormalities are implicated in schizophrenia, the neurologic conditions in which hallucinations may occur, the neurochemical contexts that are associated with hallucinations, and the methodologic details of the functional neuroimaging techniques employed. Bottom-up and top-down functional neuroimaging strategies for the investigation of schizophrenic hallucinations with positron emission tomography (PET), single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI) are reviewed. Bottom-up approaches start with or measure the biology associated with hallucinations. Top-down approaches start from the specific neuropsychological dysfunctions thought to be associated with hallucinations. The distributed brain regions, systems and functions implicated in schizophrenic hallucination formation are then discussed in the context of an integration of bottom-up and top-down approaches. Focus is placed upon abnormalities in the functions of, and interactions among, auditory-linguistic association cortices, caudal and rostral limbic/paralimbic systems, prefrontal cortices, ventral striatum and (non-specific projection and associative) thalamic nuclei, as well as upon the glutamatergic, GABAergic and ventral tegmental dopaminergic modulation of these systems.
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PMID:Functional neuroimaging of hallucinations in schizophrenia: toward an integration of bottom-up and top-down approaches. 915 29

Schizophrenia remains mainly an enigma for clinicians and researchers, and all levels of possible further comprehension should be explored. A fundamental characteristic existential perplexity in schizophrenia has significant bearing on the patient's suffering and functional decline, and deserves the attention of mental health professionals. Early detection, diagnosis and treatment might all profit from an explicit focus on the subjective aspects of this disorder. We developed a phenomenological and existentially oriented patient-centered programme for the diagnostic process and diagnosis mediation in schizophrenia, consistently based on self-reported patient experiences. Conventional diagnostic criteria in combination with a firm focus on additional fundamental experiential alterations constitute a framework that facilitates an open dialogue throughout the evaluation between the patient, his or her family and the therapist. The programme has been developed, adjusted and applied over five years on some 120 patients. It has strengthened diagnostic skills, precision and goal-directedness, increased the interest in precise evaluation, and deepened the theoretical understanding of early diagnosis. It is well accepted by the patients, their families and the professionals. This explicit focus on the patients' inner reality and experiences seems to vitalise the patient-therapist relationship.
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PMID:[Schizophrenia and the self--existential perspectives on comprehension and evaluation]. 1585 77

Evolutionary psychiatrists often consider schizophrenia to be an enigma: how come natural selection has not yet eliminated the so-called 'schizophrenia genes' if the disorder is fairly common, heritable and harmful for the reproductive success of its carriers? Usually, the answer is that the schizophrenic genotype is subject to some kind of balancing selection: the benefits it confers would then outbalance the obvious damage it does. However, in this paper I will show that the assumptions underlying such resolution are at least implausible, and sometimes even erroneous. First of all, I will examine some factual assumptions, in particular about schizophrenia's impact on reproductive success, its genetics, its history, and its epidemiology. Secondly, I will take a critical look at a major philosophical assumption in evolutionary psychiatric explanations of schizophrenia. Indeed, evolutionary psychiatrists take it for granted that schizophrenia is a natural kind, i.e. a bounded and objectively real entity with discrete biological causes. My refutation of this natural kind view suggests that schizophrenia is in fact a reified umbrella concept, constructed by psychiatry to cover a heterogeneous group of disorders. Therefore, schizophrenia, as we now know it, simply does not have an evolutionary history.
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PMID:Debunking evolutionary psychiatry's schizophrenia paradox. 1884 Mar 92

The cause of schizophrenia remains an enigma despite the development of effective antipsychotic drugs that act by modulating the dopaminergic and serotonergic systems in the limbic region of the brain. Although such drugs are undoubtedly clinically effective, many patients do not fully benefit from such treatments, and the side effects, such as weight gain and the exacerbation of insulin-dependent diabetes mellitus, are often problematic. In recent years, the possible cause of schizophrenia has switched from an emphasis on neurotransmitter dysfunction to possible genetic and neurodevelopmental abnormalities. The close link between the loci for insulin-dependent diabetes mellitus, human lymphocyte antigen system and schizophrenia may indicate an immune component for this disorder. This hypothesis gains further credibility from epidemiologic studies showing a link between viral infections in utero and the subsequent development of schizophrenia; the negative correlation between rheumatoid arthritis and schizophrenia gives further support to the hypothesis. Thus, the immune hypothesis of schizophrenia has developed from an understanding of the genetic, environmental and infectious sequelae that underlie the immune changes involving the cellular and humoral components of the adaptive immune system. The changes in the types of T-lymphocytes that are involved in the adaptive immune response are of particular importance. The T-helper 1 cells, that secrete interleukin-2 and interferon-gamma for example, are reduced in activity while the T-helper 2 cells, together with the macrophages, show an increased secretion of interleukins-6 and -10. As these immune changes are normalized following effective antipsychotic drug treatment, new types of antipsychotics could be developed that act directly on the imbalance in the components of the adaptive immune system. The finding that some anti-inflammatory drugs can exhibit modest antipsychotic activity is further evidence of the validity of the autoimmune nature of schizophrenia and an indication that drug development based on this concept may be a fruitful area for future research.
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PMID:Is there an immunologic basis for schizophrenia? 2047 58

This article addresses the classic enigma about schizophrenia (SZ). The disease occurs with a lifetime prevalence of 1%, 80% of which is attributable to genetic factors. Females with SZ produce 50% as many children as normals, and males with SZ produce 25%. Genetic factors responsible for SZ should behave like lethal genes. Yet the prevalence of SZ remains around 1% throughout the world. How can that be? Additionally, CATIE concluded that the response of each individual with SZ to treatment with antipsychotic agents (effectiveness, side-effect profile, or long-term prognosis) cannot be predicted. Every case seems to be unique. Several recent publications have reported increased frequencies of single-nucleotide polymorphisms (SNPs) and of copy-number variants (CNVs) containing large regions of DNA in patients with SZ. These genetic perturbations often include neurodevelopmental genes. The overwhelming majority of SNPs and CNVs are post-fertilization mutations, occurring in somatic tissue, not germinal tissue. These mutations are a normal aspect of somatic cell division but occur more frequently in patients with SZ. Somatic mutations are not passed on to subsequent generations and therefore cannot account for the inheritance of SZ. Our speculation is that the genetic platform for SZ is the gene or genes that increase the number of de novo mutations in patients with SZ. We argue that balanced polymorphism is the most plausible hypothesis to account for the preservation of non-adaptive genes in nature-and, in particular, in SZ. Maladaptive genes in different combinations can confer increased fitness to the entire population, thus insuring their preservation in the gene pool. Somatic mutations explain both the sporadic occurrence of SZ within families and the wide variations in phenotypic expression of SZ. Increased frequency of somatic mutations may confirm greater overall fitness via balanced polymorphism to explain the maintenance of the SZ gene or genes within the human population.
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PMID:Genetics of the schizophrenias: a model accounting for their persistence and myriad phenotypes. 2271 3

Two revolutionary drugs were introduced into psychiatry in the early 1950s for the treatment of agitated mental patients - reserpine and chlorpromazine. These drugs initiated the modern era of drug treatment for schizophrenia and other psychoses. Early research revealed that, although the pharmacological profiles of the two drugs overlapped considerably, they had different mechanisms of action. The mechanism of action of reserpine was determined first: it depletes monoamines from the brain and other tissues. By contrast, chlorpromazine has little or no effect on brain monoamine concentrations. The mystery created by two drugs that have similar pharmacological profiles but different mechanisms of action is the chlorpromazine enigma. For about eight years after the mechanism of action of reserpine was determined, researchers followed several false leads about the mechanism of action of chlorpromazine. Then, in 1963, Arvid Carlsson and Margit Lindqvist proposed that chlorpromazine (and haloperidol) work by blocking "monoaminergic" receptors. It was quickly determined that dopamine receptor blockade was the most important action. Although the idea of chemical communication between central neurons had yet to gain wide acceptance, this idea was central to resolving the chlorpromazine enigma.
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PMID:The chlorpromazine enigma. 2332 29

Brain oscillations reflect pattern formation of cell assemblies' activity, which is often disturbed in neurological and psychiatric diseases like depression, schizophrenia and stroke. In the neurobiological analysis and treatment of these conditions, transcranial electric currents applied to the brain proved beneficial. However, the direct effects of these currents on brain oscillations have remained an enigma because of the inability to record them simultaneously. Here we report a novel strategy that resolves this problem. We describe accurate reconstructed localization of dipolar sources and changes of brain oscillatory activity associated with motor actions in primary cortical brain regions undergoing transcranial electric stimulation. This new method allows for the first time direct measurement of the effects of non-invasive electrical brain stimulation on brain oscillatory activity and behavior.
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PMID:In vivo assessment of human brain oscillations during application of transcranial electric currents. 2378 80


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