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)

Animal data indicate that melatonin secretion is stimulated by the paraventricular nucleus (PVN) of the hypothalamus and that lesions of the PVN mimic the endocrine effects of pinealectomy. Since the PVN lies adjacent to the third ventricle, I propose that periventricular damage, which is found in schizophrenia and may account for the third ventricular dilatation seen on computed tomographic (CT), may disrupt PVN-pineal interactions and ultimately enhance the process of pineal calcification (PC). To investigate this hypothesis, I conducted CT study on the relationship of PC size to third ventricular width (TVW) in 12 chronic schizophrenic patients (mean age: 33.7 years; SD = 7.3). For comparison, I also studied the relationship of PC size to the ventricular brain ratio and prefrontal cortical atrophy. As predicted, there was a significant correlation between PC size and TVW (r pbi = .61, p < .05), whereas PC was unrelated to the control neuroradiological measures. The findings support the hypothesis that periventricular damage may be involved in the process of PC in schizophrenia and may indirectly implicate damage to the PVN in the mechanisms underlying dysfunction of the pineal gland in schizophrenia. In a second study, I investigated the prevalence of habenular calcification (HAC) on CT in a cohort of 23 chronic schizophrenic-patients (mean age: 31.2 years; SD = 5.95). In this sample HAC was present in 20 patients (87%). Since the prevalence of HAC in a control population of similar age is only 15% these data reveal an almost 6-fold higher prevalence of HAC (X2 = 84.01, p < .0001) in chronic schizophrenia as compared to normal controls. The implications of HAC for the pathophysiology of schizophrenia are discussed in light of the central role of the habenula in the regulation of limbic functions.
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PMID:Pineal and habenula calcification in schizophrenia. 130 34

Since the first designation by E. Bleuler, various etiopathogenic theories have been proposed in schizophrenia. The dopaminergic hyperactivity hypothesis remains the more valid one. Recently, a neurodevelopmental hypothesis has been suggested in schizophrenia. This hypothesis postulates an early disturbance in the development of central nervous system, mainly in the temporo-limbic areas. This disturbance is not secondary to a degenerative process. It may take place during the end of the second trimester of the pregnancy and be complete at the time of puberty. Genetic and environmental factors co-occur to explain these brains developmental disturbances. This hypothesis has been formulated according to a tremendous amount of various data obtained with different methodologies. Neuropathological techniques observed a reduction in the number of cells and cyto-architectural anomalies in different brain areas such as hippocampus and para-hippocampus gyrus. The lack of associated gliosis suggests an early phenomenon developing before birth. Structural brain abnormalities have been demonstrated using various neuroimaging techniques. Computed tomographic scanning and magnetic resonance imaging reveal structural anomalies such as ventricular dilatation, and positron emission tomography functional ones such as frontal hypometabolism. These results appear to be unrelated to the severity, the duration and the treatment of the disease. More informations are needed to eventually confirm this hypothesis. Clinical, cognitive and neuropsychological data have to be completed. Longitudinal studies are urgently needed using clinical, epidemiological, genetic and neuroimaging techniques.
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PMID:[Towards a neurodevelopmental hypothesis in schizophrenia]. 163 96

Several recent computed tomographic (CT) studies have provided evidence for structural cerebral abnormalities in schizophrenia. CT scan findings included enlargement of the lateral cerebral ventricles, cortical atrophy, third ventricular dilatation, ventricular asymmetry, and cerebellar atrophy. In addition, there is increasing data to suggest that abnormal pineal melatonin functions are associated with the pathophysiology of schizophrenia. To explore further the relationship of the pineal gland to the pathophysiology of schizophrenia and its specific association with structural abnormalities, we investigated: (a) the relationship of pineal calcification (PC) to computerized tomographic (CT) scan measurements of cortical and subcortical atrophy in 41 chronic schizophrenic patients, and (b) the relationship of PC size to CT scan measurements and cortical and subcortical atrophy in 51 chronic schizophrenic patients. Results of the first study revealed that the presence of PC was significantly associated with measurements of prefrontal cortical atrophy (p less than .01), while there was no association with measurements of parieto-occipital atrophy, sulcal prominence, or ventricular brain ratio (VBR). These findings support the notion that the various structural brain abnormalities in schizophrenia may reflect different pathological processes and that abnormal pineal melatonin functions may be associated with the pathophysiology of prefrontal cortical atrophy. In addition, since some clinical facets of schizophrenia covary with frontal lobe dysfunction, our findings highlight the significance of abnormal pineal functions for the pathophysiology of schizophrenia. In the second study we found a significantly higher prevalence of pathologically enlarged PC (i.e., greater than 1 cm in diameter) in schizophrenia as compared to controls of similar age. In addition, we found a significant association between CT scan measurements of cortical atrophy and pathologically enlarged PC size (p less than .05). By contrast, PC size was unrelated to VBR. These findings demonstrate a specific association between pathologically enlarged PC and cortical atrophy in schizophrenia. The implications of these findings to the pathophysiology of schizophrenia and, specifically, to the morphological abnormalities that accompany the disease are discussed.
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PMID:The relationship of pineal calcification to cortical atrophy in schizophrenia. 193 61

Tc-99m hexamethylpropylene amineoxime (HMPAO) was used to image cerebral perfusion changes in 20 patients with chronic schizophrenia (19 male and 1 female, aged 22-48, at an average age of 29.0). All were being given neuroleptic drugs. Twelve had electroconvulsive therapy. In addition, all had abnormal studies except one, who was normal and had a poor response to treatment. Ventricular dilatation and cerebral atrophy was seen in eleven patients, and 77 focal lesions were detected. Forty-two lesions demonstrated increased HMPAO retention, which was distributed as follows: 26 in the basal ganglia in 14 patients (12 bilateral, 2 unilateral); 10 along the sylvian fissure in the parietotemporal region; and 3 in the frontal and 1 in each of the temporal, parietal, and occipital regions. Thirty-five focal lesions exhibited decreased perfusion: ten parietal, eight frontal, seven temporal, six cerebellar, and four occipital lobes. This study demonstrates the potential value of Tc-99m HMPAO in schizophrenia and other psychiatric disorders.
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PMID:Cerebral perfusion changes in schizophrenic patients using Tc-99m hexamethylpropylene amineoxime (HMPAO). 238 38

A 14-year-old youth sustained an injury to the left frontoparietal area, which was followed by evident change in personality and subsequently by an early-onset schizophrenia-like psychosis. Magnetic resonance imaging revealed ventricular dilatation, slightly more marked in the left hemisphere, and cortical atrophy. Some implications of this case for research on schizophrenia itself are discussed.
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PMID:'Early-onset schizophrenia' after teenage head injury. A case report with magnetic resonance imaging. 325 Jun 79

To explore associations between psychiatric symptoms and cerebral magnetic resonance imaging abnormalities in low-birth-weight adolescents, 55 very low-birth-weight (<or=1500 gm), 54 term small for gestational age (birth weight <10th centile) and 66 term control adolescents (birth weight >or=10th centile) were assessed at 14-15 years of age. Outcome measures were Schedule for Affective Disorders and Schizophrenia for School-Age Children, Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Autism Spectrum Screening Questionnaire, and qualitatively assessed cerebral magnetic resonance images. The very low-birth-weight group manifested increased prevalence of psychiatric symptoms and disorders compared with controls (P < 0.001), especially symptoms of attention-deficit/hyperactivity disorder, and high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The Attention-Deficit/Hyperactivity Disorder Rating Scale score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with control subjects, but not more frequent abnormalities on cerebral magnetic resonance imaging. In conclusion, attention-deficit/hyperactivity disorder symptoms were significantly associated with white matter reduction and thinning of corpus callosum in very low-birth-weight adolescents. No associations were found for other psychiatric symptoms and brain abnormalities in any of the groups.
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PMID:Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities. 1619 24

The normal pattern of cerebral asymmetry may be altered in neurodevelopmental disorders such as autism and schizophrenia. Babies born very preterm have an increased risk of brain damage, and brain abnormalities which persist into adolescence. This study aimed to ascertain whether preterm birth affects the development of fronto-occipital asymmetry. Structural MRI (magnetic resonance imaging) scans from 14 year old individuals born very preterm (n = 61; mean age 14 years 11 months; 29 male) and age-matched full-term controls (n = 49; mean age 14 years 11 months; 31 male) underwent morphometric analysis, using well-validated stereological methods. Measurements of right and left prefrontal, premotor, sensorimotor and occipitoparietal regional volumes were made and asymmetry indices calculated. These factors underwent a reductive factor analysis. There were no significant between-group differences in fronto-occipital asymmetry between the preterm adolescents and their full-term counterparts. It seems unlikely, therefore, that preterm birth per se deviates the development of normal fronto-occipital asymmetry. Neonatal periventricular haemorrhage with ventricular dilatation revealed by ultrasound may be associated with reversal of asymmetry in the sensorimotor area.
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PMID:Cerebral asymmetry in 14 year olds born very preterm. 1669 55

This is the case of a young man suffering from schizophrenia and treated with clozapine. He developed acute heart failure associated with pericardial effusion and midventricular dyskinesia with severe systolic dysfunction and left ventricular dilatation at echocardiogram, readily resolved after the suspension of clozapine therapy. The segmental wall motion abnormalities observed at echocardiogram in this case are peculiar and have never been described before. The possible cardiotoxic effects of clozapine have been reported previously in the literature. Because of its serious potential side effects this drug is not considered the first choice for treatment of schizophrenia. Before beginning treatment, patients should undergo a cardiac evaluation, and they should also be periodically followed up with echocardiograms.
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PMID:Midventricular dyskinesia during clozapine treatment? 1982 27

Loss of function mutations in human Oligophrenin1 (OPHN1) gene are responsible for syndromic intellectual disability (ID) associated with cerebellar hypoplasia and cerebral ventricles enlargement. Functional studies in rodent models suggest that OPHN1 linked ID is a consequence of abnormal synaptic transmission and shares common pathophysiological mechanisms with other cognitive disorders. Variants of this gene have been also identified in autism spectrum disorder and schizophrenia. The advanced understanding of the mechanisms underlying OPHN1-related ID, allowed us to develop a therapeutic approach targeting the Ras homolog gene family, member A (RHOA) signalling pathway and repurpose Fasudil- a well-tolerated Rho Kinase (ROCK) and Protein Kinase A (PKA) inhibitor- as a treatment of ID. We have previously shown ex-vivo its beneficial effect on synaptic transmission and plasticity in a mouse model of the OPHN1 loss of function. Here, we report that chronic treatment in adult mouse with Fasudil, is able to counteract vertical and horizontal hyperactivities, restores recognition memory and limits the brain ventricular dilatation observed in Ophn1-/y However, deficits in working and spatial memories are partially or not rescued by the treatment. These results highlight the potential of Fasudil treatment in synaptopathies and also the need for multiple therapeutic approaches especially in adult where brain plasticity is reduced.
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PMID:Fasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability. 2714 43

Clozapine-induced cardiomyopathy is a rare but fatal complication with a reported incidence of 0.4% in Japan. Clozapine-induced cardiomyopathy develops at an average of 14.4 months after initiating clozapine, and to our knowledge, has a duration no longer than seven years. We present a patient who developed dilated cardiomyopathy after 17 years of clozapine treatment and made a full recovery of cardiac function at 40 weeks after clozapine treatment cessation. A 43-year-old male with a 24-year history of schizophrenia was treated with clozapine (600 mg/day) for 17 years. No abnormal findings were revealed at follow up until he pre- sented with dyspnea with no accompanying symptoms while walking. He was suspected of worsening asthma due to his past history and lack of abnormalities of ECG and CXR. However, as he experienced gradually worsening dyspnea accompanied by listlessness and lightheaded- ness, he was referred to a cardiologist. The echocardiogram revealed left ventricular dilatation and systolic dysfunction (left ventricular ejection fraction, LVEF=40%), which made a diagno- sis of dilated cardiomyopathy. We excluded cardiac ischemia and other possible causes of dilated cardiomyopathy with cardiac catheterization and endomyocardial biopsy. Clozapine treatment was stopped and switched to olanzapine along with standard heart failure medica- tions. The symptoms and left ventricular function improved following clozapine discontinua- tion. The symptoms resolved and echocardiogram showed a LVEF of 50% within 11 weeks after treatment with clozapine was ended. LVEF was reported at 59% 40weeks after cessation of clozapine. At the present time, 32 months since ceasing clozapine treatment, no worsening of symptoms has been presented. After ceasing clozapine and inducing standard heart failure medications, the patient presented the excellent recovery and the normalization of his echocar- diogram. Despite this outcome, there is currently insufficient evidence to conclusively establish a causal relationship between clozapine and cardiomyopathy in this case. In addition, this case demonstrates that we cannot exclude cardiomyopathy due to lack of abnormal findings of ECG and CXR. Therefore, we recommend that echocardiograms should be performed annually. The mortality associated with clozapine-induced cardiomyopathy is high, so if patients undergoing therapy with clozapine develop new symptoms or signs suggestive of cardiac dysfunction such as dyspnea, a focused cardiovascular examination should be considered.
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PMID:[A Case of Dilated Cardiomyopathy after 17 Years of Clozapine Treatment]. 3062 Aug 27


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