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

Cerebrospinal fluids (CSF) from 35 patients with senile or presenile dementia and from 13 patients with schizophrenia and related syndromes were examined in cell cultures with the aim to isolate Herpesvirus hominis 1 (HVH 1) or other viruses. Serum and CSF antibodies to HVH 1 and/or interferon in the patients indicated a recent HVH 1 antigenic or viral activity. In the CSF of two senile demented patients and of one patient with schizoaffective psychosis, agents of low virulence, causing a cytopathic effect in 3 or 4, but not more, subsequent passages were detected and identified as HVH 1 by immunofluorescence. A focus of cells containing HVH 1 antigen at the cell membrane and in cytoplasm was visualized by immunofluorescence in an explant from nucleus amygdalae from 1 of 6 patients with schizophrenia and related syndromes examined. In the original biopsy materials, various virus-like structures were found in nuclei and cytoplasm of astrocytes and neurocytes and in axons in the neuropil.
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PMID:Latent herpesvirus hominis 1 in the central nervous system of psychotic patients. 4 36

Accurate volume determination of the encephalic ventricles is of importance in several clinical conditions, including Alzheimer's presenile dementia, schizophrenia, and benign intracranial hypertension. Previous studies have investigated the accuracy with which magnetic resonance imaging (MRI) can be used in clinical practice to evaluate the encephalic ventricles. However, adequate evaluation of pathological conditions depends on a sufficient amount of morphometric data from normal subjects. To begin establishing this data base for "normal" subjects, we evaluated the MRI scans of 38 subjects found to have no apparent pathology and calculated the ventricular volume in each case by using methods previously developed in our laboratory. The results were then compared with published volumes determined from studies that used either ventricular casts or computerized tomographic scans. The average total ventricular volume for all 38 subjects was 17.4 cm3, while that for males was 16.3 cm3 and that for females was 18.0 cm3. A small but significant correlation was found between age of subject and ventricular volume, with ventricular size increasing with age.
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PMID:Evaluation of encephalic ventricular volume from the magnetic resonance imaging scans of thirty-eight human subjects. 209 64

An investigation of all patients (with the exception of alcoholics) residing in a city district and registered at a psychoneurological dispensary revealed that after 40 years the disease began in almost one-fourth of the cases (24.7%). In the majority of cases (56%) these were diseases characteristic of the second half of life: vascular pathology (45.3%), involutional psychoses (6.6%), presenile dementia (2.2%) and senile dementia (1.9%). Other findings included schizophrenia in 24.3%, manic-depressive psychoses in 2.7%, psychogenias in 7.6%, consequences of head trauma in 2.2% and other exogenias in 3.7%. The clinical and social parameters of the prognosis in mental diseases first expressed after 40 years of age were on the whole lower but they reflected the modern tendency to attenuation of pathological manifestations: by the time of examination the status of 48% of patients was characterized by intermission or syndromes of a nonpsychotic level.
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PMID:[Structure of mental diseases of the 2d half of life according to the results of an epidemiologic study]. 377 18

Deletions in the DAP12 gene in humans result in Nasu-Hakola disease, characterized by a combination of bone fractures and psychotic symptoms similar to schizophrenia, rapidly progressing to presenile dementia. However, it is not known why these disorders develop upon deficiency in DAP12, an immunoreceptor signal activator protein initially identified in the immune system. Here we show that DAP12-deficient (DAP12(-/-)) mice develop an increased bone mass (osteopetrosis) and a reduction of myelin (hypomyelinosis) accentuated in the thalamus. In vitro osteoclast induction from DAP12(-/-) bone marrow cells yielded immature cells with attenuated bone resorption activity. Moreover, immature oligodendrocytes were arrested in the vicinity of the thalamus, suggesting that the primary defects in DAP12(-/-) mice are the developmental arrest of osteoclasts and oligodendrocytes. In addition, the mutant mice also showed synaptic degeneration, impaired prepulse inhibition, which is commonly observed in several neuropsychiatric diseases in humans including schizophrenia, and aberrant electrophysiological profiles in the thalami. These results provide a molecular basis for a unique combination of skeletal and psychotic characteristics of Nasu-Hakola disease as well as for schizophrenia and presenile dementia.
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PMID:Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. 1256 53

Cells at the maternal-fetal interface express indoleamine 2,3 dioxygenase (IDO) to consume all local tryptophan for the express purpose of starving adjacent maternal T cells of this most limiting and essential amino acid. This stops local T cell proliferation to ultimately result in the most dramatic example of immune tolerance, acceptance of the fetus. By contrast, inhibition of IDO using 1-methyl-tryptophan causes a sudden catastrophic rejection of the mammalian fetus. Immunomodulatory factors including IFNgamma, TNFalpha, IL-1, and LPS use IDO induction in responsive antigen presenting cells (APCs) also to transmit tolerogenic signals to T cells. Thus it makes sense to consider IDO induction towards tolerance for autoimmune diseases in general. Approaches to cell specific therapeutic IDO induction with NAD precursor supplementation to prevent the collateral non-T cell pathogenesis due to chronic TNFalpha-IDO activated tryptophan depletion in autoimmune diseases are reviewed. Tryptophan is an essential amino acid most immediately because it is the only precursor for the endogenous biosynthesis of nicotinamide adenine dinucleotide (NAD). Both autoimmune disease and the NAD deficiency disease pellagra occur in women at greater than twice the frequency of occurrence in men. The importance of IDO dysregulation manifest as autoimmune pellagric dementia is genetically illustrated for Nasu-Hakola Disease (or PLOSL), which is caused by a mutation in the IDO antagonizing genes TYROBP/DAP12 or TREM2. Loss of function leads to psychotic symptoms rapidly progressing to presenile dementia likely due to unchecked increases in microglial IDO expression, which depletes neurons of tryptophan causing neurodegeneration. Administration of NAD precursors rescued entire mental hospitals of dementia patients literally overnight in the 1930's and NAD precursors should help Nasu-Hakola patients as well. NAD depletion mediated by peroxynitrate PARP1 activation is one of the few established mechanisms of necrosis. Chronic elevation of TNFalpha leading to necrotic events by NAD depletion in autoimmune disease likely occurs via combination of persistent IDO activation and iNOS-peroxynitrate activation of PARP1 both of which deplete NAD. Pharmacological doses of NAD precursors repeatedly provide dramatic therapeutic benefit for rheumatoid arthritis, type 1 diabetes, multiple sclerosis, colitis, other autoimmune diseases, and schizophrenia in either the clinic or animal models. Collectively these observations support the idea that autoimmune disease may in part be considered as localized pellagra manifesting symptoms particular to the inflamed target tissues. Thus pharmacological doses of NAD precursors (nicotinic acid/niacin, nicotinamide/niacinamide, or nicotinamide riboside) should be considered as potentially essential to the therapeutic success of any IDO-inducing regimen for treating autoimmune diseases. Distinct among the NAD precursors, nicotinic acid specifically activates the g-protein coupled receptor (GPCR) GPR109a to produce the IDO-inducing tolerogenic prostaglandins PGE(2) and PGD(2). Next, PGD(2) is converted to the anti-inflammatory prostaglandin, 15d-PGJ(2). These prostaglandins exert potent anti-inflammatory activities through endogenous signaling mechanisms involving the GPCRs EP2, EP4, and DP1 along with PPARgamma respectively. Nicotinamide prevents type 1 diabetes and ameliorates multiple sclerosis in animal models, while nothing is known about the therapeutic potential of nicotinamide riboside. Alternatively the direct targeting of the non-redox NAD-dependent proteins using resveratrol to activate SIRT1 or PJ34 in order to inhibit PARP1 and prevent autoimmune pathogenesis are also given consideration.
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PMID:Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease. 1743 Jan 13

Niemann-Pick disease type C is a rare lipid trafficking disorder characterized by the accumulation of cholesterol and glycosphingolipids in the brain and viscera. Perinatal, early infantile, late infantile, juvenile and adult forms are distinguished based on the age of manifestation. In the juvenile form, patients in their early years are usually, but not always, symptom free, but present with neurodegeneration later in their lives. These include clumsiness, ataxia, seizures, motor and intellectual decline. Psychiatric manifestations may occur at any stage of the disease. These manifestations include schizophrenia, presenile dementia, depression or psychosis. In 2009, miglustat was approved for the therapy of the disease. We present a case of a patient with juvenile Niemann-Pick C disease whose psychosis was reversed completely by miglustat treatment. Based on our clinical experience we suggest considering Niemann-Pick C in cases of therapy-resistant psychosis and encourage the introduction of miglustat in Niemann-Pick C patients even in the most advanced cases, with respect to psychiatric illness.
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PMID:Complete recovery from psychosis upon miglustat treatment in a juvenile Niemann-Pick C patient. 2411 81