Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical and biochemical characteristics of metachromatic leukodystrophy (MLD), true adult forms and late juvenile forms which are still living at adulthood, are reviewed as they both are observed in adult Neurology and Psychiatry departments. Mental deterioration is often the first symptom, evolving progressively; and dementia finally occurs. The latency before the appearance of neurological objective symptoms may be long and extend for several years. In many cases, the behavioral abnormalities are the first symptoms. Some of these forms have been diagnosed as schizophrenia. Very seldom, neurological symptoms, especially ataxia, occur without cognitive or psychiatric disturbances. Most of these cases have pyramidal and cerebellar symptoms, at diverse degrees. Seizures can also occur which is some cases can be early symptoms associated to mental deterioration. The association of central and peripheral neurological symptoms is very characteristic of MLD. The peripheral neuropathy is not generally clinically evidenced, but is rarely missing electrophysiologically. Arylsulfatase A determination should be performed for diagnosis as a first step, and confirmed by the accumulation of sulfatide, either by quantitative determinations in urine or by the sulfatide loading test. It is as yet not clear why certain forms have a rather rapid evolution in 5 years, and others have a very protracted course during decades.
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PMID:Adult forms of metachromatic leukodystrophy: clinical and biochemical approach. 168 76

Patients with adult-onset metachromatic leukodystrophy (MLD) often present with personality changes or deterioration of cognitive functions. Although rare, this form of MLD should be included in the differential diagnosis of psychotic and dementing disorders. The following case report describes a 38-year-old man with adult-onset MLD, who carried the diagnosis of schizophrenia and was treated as a schizophrenic for a number of years. Metachromatic leukodystrophy was initially suspected because of white matter abnormalities detected on computed tomographic scans and magnetic resonance images of the brain. The diagnosis of MLD was confirmed by the discovery of markedly reduced leukocyte arylsulfatase A activity. The computed tomographic and magnetic resonance imaging findings in MLD are reviewed.
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PMID:Adult metachromatic leukodystrophy. Value of computed tomographic scanning and magnetic resonance imaging of the brain. 381 37

A 32-year-old woman with a 12-year history of schizophrenia demonstrated symmetrical bifrontal and biparietal periventricular hypodensities on computed tomographic scan. Sural nerve biopsy and urine and leukocyte enzyme assay confirmed the diagnosis of metachromatic leukodystrophy. The computed tomographic correlate in an adult with metachromatic leukodystrophy in whom the psychiatric manifestations were the predominant clinical feature is described.
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PMID:Metachromatic leukodystrophy manifesting as a schizophrenic disorder: computed tomographic correlation. 403 56

Two of the favorite hypotheses of schizophrenia research-maldevelopment of cerebral cortex and malfunction of brain dopamine systems-have often seemed difficult to reconcile. This article reviews recent research that suggests a heuristically useful reconciliation centered on the functional neuroanatomical concept of prefrontal-temporolimbic cortical connectivity. Anatomical findings from postmortem studies and neuropsychological and neuroimaging studies of brain function in patients with schizophrenia have implicated a developmental 'dysconnection' of temporolimbic-prefrontal cortices. The possibility that such dysconnection can account for the principal phenomenology of the illness, including its delayed onset and its treatment, is suggested by neurologic disease analogies such as metachromatic leukodystrophy and by recent studies in animals with developmental cortical lesions. Studies mapping neuronal gene expression indicate that all antipsychotic drugs modulate DNA transcription in a region of the nucleus accumbens that receives converging inputs from prefrontal and temporolimbic cortices, suggesting that indirect compensation for dysfunctional communication between prefrontal and temporolimbic cortices is a therapeutic mechanism of these drugs. Treatments aimed at direct cortical compensation may be more effective.
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PMID:Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground. 757 73

Patients with metachromatic leukodystrophy (MLD) of juvenile or adult onset present with behavioral abnormalities. In nine patients, diagnosed between ages 11 and 33 years, behavior and neuropsychological test results disclosed a pattern of dementia combining features associated with both frontal and white matter abnormalities. All the patients had been considered to have a psychiatric disorder prior to the diagnosis of MLD, even though none had any of the cardinal features of schizophrenia or other major psychosis. Early diagnosis of late-onset MLD is important to provide access to appropriate effective therapy.
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PMID:Characteristics of the dementia in late-onset metachromatic leukodystrophy. 816 21

Computer simulations of parallel distributed processing (PDP) neural networks have increased our understanding of brain functioning. This article reviews how PDP concepts can contribute to our understanding of schizophrenic symptoms. Psychotic states induced by phencyclidine and the adult form of metachromatic leukodystrophy, as well as neurometabolic studies, suggest that schizophrenia reflects a breakdown in communication between cortical areas. A computer simulation of this type of brain pathology has suggested two neurocognitive consequences: some cortical circuits will become functionally autonomous, and a subset of these circuits will yield "parasitic foci" that slavishly reproduce the same cognitive output. Delusions of control, paranoid delusions of the idee fixe type, thought broadcasting, "voices," and certain deficit symptoms are postulated outcomes of parasitic foci located at different levels of language processing. A neurodevelopmental model of impaired corticocortical communication is described, and this model's implications for further study are outlined.
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PMID:Parallel distributed processing and the emergence of schizophrenic symptoms. 808 28

Metachromatic leukodystrophy (MLD) is a degenerative disease caused by the deficiency of aryl sulfatase (ASA). It can course with psychiatric symptoms. We determined the prevalence of ASA deficiency in a group of 23 patients with presumable schizophrenia. The median serum ASA was 53.2 nmol/mL/h (range 3.3-152.5). Six patients (26%) showed low ASA activity (< 27.5 nmol/mL/h which is the lowest value observed in 29 normal controls); five of them had clinical history of delusions of grandeur, auditive hallucinations, multiple hospitalizations, low response to neuroleptics, and abnormal evoked potentials. It is probable that the schizophrenic symptoms in these patients may be due to the enzyme deficiency. We conclude that the assay is useful in clinical practice as it may help to identify cases of MLD in patients with suspected schizophrenia.
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PMID:[Activity of aryl sulfatase A enzyme in patients with schizophrenic disorders]. 858 9

A 26-year-old Japanese woman slowly developed a change of character such as hypospontaneity and blunted affect, followed by obvious mental deterioration. She was diagnosed as having a disorganized type of schizophrenia at the first examination. Brain magnetic resonance imaging demonstrated diffuse high intensity in the cerebral white matter, particularly in the frontal lobes. The single photon emission computed tomography images using 123I-IMP disclosed diffuse cerebral hypofusion, especially in the frontal lobes. Electroencephalogram showed a moderate amount of 5-6Hz theta waves on the background of alpha activity. Nerve conduction velocities in the extremities were delayed. The level of leucocyte arylsulphatase was low. In the arylsulphatase A gene analysis, a compound heterozygote having the 99Gly-->Asp and 409Thr-->Ile mutations was confirmed. The patient was diagnosed as having metachromatic leukodystrophy. She gradually showed obvious dementing symptoms such as memory disturbance and disorientation. The characteristics of the psychiatric symptoms in the leukodystrophy are discussed.
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PMID:Adult-type metachromatic leukodystrophy with a compound heterozygote mutation showing character change and dementia. 1045 47

Previous studies have suggested that arylsulphatase A (ASA) deficiency may be present in psychiatric patients. A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. Metachromatic leucodystrophy (MLD) is a disease caused by deficiency of the enzyme ASA. Clinically, adult MLD may present as a schizophrenia-like psychosis, deterioration of cognitive functions, personality changes, depression and dementia. However, there are individuals with low ASA activity without clinical symptoms of MLD. This state is described as ASA pseudodeficiency. It remains controversial whether low ASA activity predisposes to or influences the development of psychiatric symptoms. Relatively little attention has been paid to the role of neurodegenerative processes in the pathophysiology of psychiatric disorders. The hypothesis underlying this work is that there is a subclass of mentally ill patients whose psychiatric problems are at least partly caused by an abnormal ASA. The purpose of this particular study was to determine whether an abnormal ASA could be detected in schizophrenic, major depressed and demented patients and control subjects. There were 66 schizophrenic, 59 major depressed and 61 demented patients. The control group consisted of 102 healthy volunteers. Leucocyte ASA activity was determined from blood samples, using p-nitrocatechol sulphate as substrate. Our results show that low ASA activity is more frequently found in psychiatric patients than in control subjects. Our findings indicate that clinical types of major depression and schizophrenia could be connected with low ASA activity. The presence of a decreased ASA activity points to the conclusion that an enzyme deficit entails vulnerability to psychiatric disorders.
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PMID:Low arylsulphatase A activity in the development of psychiatric disorders. 1117 49

Metachromatic leukodystrophy (MLD) is a recessive autosomal disease which is biochemically characterized by an accumulation of sulfatides (sulfogalactosylceramides) mainly in oligodendrocytes and macrophages/microglia. The deficient enzyme is a lysosomal hydrolase, cerebroside sulfate sulfatase (arylsulfatase A). MLD is both a dysmyelinating and a demyelinating disease. The main clinical forms are infantile or juvenile, but some forms appear at adulthood. This disease involves also neuronal cells as sulfatides are also present in neurons in which the defect in degradation occurs also. We have studied 12 cases of adult MLD and clearly distinguished two clinical forms. One of them was characterized by mainly central nervous system motor signs (pyramidal, cerebellar, and seldom dystonia) and a peripheral neuropathy. The other form always started by behavioural abnormalities with modifications of mood, peculiar social reactions; a progressive mental deterioration occurred also. The diagnosis of schizophrenia was often mentioned. Most of these patients remained for many years without any neurological symptoms, and the diagnosis was only made when neurological signs appeared, or when Magnetic Resonance Imaging (MRI) was performed. MRI showed a diffuse demyelination, bilateral and often symmetrical, which could be temporarily limited to the periventricular areas. The diagnosis of adult MLD was biochemical, evidencing the low activity of arylsulfatase A (ASA) and sulfatide accumulation. To determine the respective participation of neurons and glial cells in the physiopathology of both the motor forms and the psycho-cognitive forms, our first approach was to search for mutations differing according to the clinical status. Motor forms involved the major adult ASA mutation P426L in a homozygote form in contrast to psycho-cognitive forms which involved as a compound heterozygote a specific I179S mutation.
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PMID:Motor and psycho-cognitive clinical types in adult metachromatic leukodystrophy: genotype/phenotype relationships? 1244 9


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