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)

Schizophrenia is a heterogeneous disease involving genetic and environmental factors. The frequency of structural brain abnormalities or physical anomalies supports a neurodevelopmental etiology, especially in early onset schizophrenia. Brain-Derived-Neurotrophic-Factor (BDNF) is involved in the neurodevelopment of dopaminergic (DA)-related systems and interacts with the meso-limbic DA systems, involved in the therapeutic response to antipsychotic drugs and substance abuse. In addition, BDNF promotes and maintains dopamine D3 receptor (DRD3) expression. In a French Caucasian population, we found no statistical difference in allele or genotype distribution of the BDNF gene dinucleotide repeat polymorphism (166-174 bp) between the whole group of schizophrenic patients and controls. By contrast, an excess of the 172-176 bp alleles was found in patients with late onset, in neuroleptic-responding patients and in non-substance-abusing patients. BDNF gene variants thus appear to be associated with developmental features of schizophrenia. In addition, this association with good treatment responding was independent from the association found with the DRD3 Ball gene polymorphism in the same population. These results suggest an independent contribution of each gene to a treatment-sensitive form of schizophrenia.
 ...
PMID:Brain derived neurotrophic factor (BDNF) gene variants association with age at onset and therapeutic response in schizophrenia. 1103 92

Few magnetic resonance imaging studies of schizophrenia have investigated brain tissue volumes and their relation to clinical symptoms in patients with an early age at illness onset. The twofold purpose of the study was to investigate both gray and white matter volumes in schizophrenic men with an early age at illness onset, and to determine whether clinical features correlated with tissue volume changes, using an automated voxel-by-voxel image analysis procedure. Twenty male patients with DSM-IV diagnoses of schizophrenia, and an early age at onset (m+/-SD=19+/-2) were compared with 20 age-matched health men. Magnetic resonance (1.5-T) scans were obtained with an Inversion-Recovery prepared fast gradient echo sequence enhancing gray and white matter contrast. Statistical Parametric Mapping was used for image segmentation and comparison. Patients had significant gray matter reductions in medial frontal gyri, left insula, left parahippocampus, and left fusiform gyrus; bilateral white matter reductions in frontal lobes, and increased total cerebrospinal fluid volume were also observed. Negative symptom scores were negatively related to white matter volumes in cingulate regions, and in the right internal capsule. These findings emphasize a pattern of left-hemisphere gray matter abnormalities, and suggest that fronto-paralimbic connectivity may be altered in men with early onset schizophrenia.
 ...
PMID:Cerebral gray and white matter reductions and clinical correlates in patients with early onset schizophrenia. 1137 11

This review discusses functional and structural brain abnormalities in childhood-onset schizophrenia identified by neuroimaging techniques. Published literature regarding both morphological and functional neuroimaging is discussed, regarding also the diversity of neuroimaging findings which partly reduces their reliability. The findings in early onset schizophrenia are compared with those of adult patients. The results of long-term investigations of structural abnormalities in early onset schizophrenia are given particular attention. The most consistent findings are ventricular enlargement and reduced total brain volume. Further, volumetric changes in the temporal and frontal cortex, thalamus, basal ganglia and limbic system are reported, as are hemispheric asymmetries and, conversely, reduction of normal differences. Findings regarding the corpus callosum and cerebellum are less consistent. In patients whose schizophrenia commenced in early childhood, the differences were generally more marked than in adolescence- or adult-onset schizophrenia. Atrophy of total brain volume was progressive throughout the course of the disorder. It is probable that neuroanatomical cerebral abnormalities present prior to disease onset play an etiopathogenic role in the development of schizophrenia.
 ...
PMID:Structural brain abnormalities specific to childhood-onset schizophrenia identified by neuroimaging techniques. 1207 63

The present article reviews the specific problems of the off-label use of atypical and typical neuroleptics in the treatment of adolescent patients with schizophrenia. There is a considerable gap in the empirical knowledge of treatment efficacy and long term safety in adult populations as compared to children and adolescents. This means that in most in-patients with early onset schizophrenia some sort of typical or atypical neuroleptic drug is currently used beyond license. From a legal point of view there is no protection for treated children or adolescents and their parents as the manufacturer of these pharmaceutical products does not assume liability for off-label use. Whether the doctor can be held liable in these cases, depends on the quality of the information he provides to his patients and the patients' consent. Legal changes such as the Food and Drug Administration Modernization Act (FDAMA) and Pediatric Rule in the USA have brought forward more research to the benefit of children and adolescents. In 2002 a trend has been noticed in both the European and the German Parliament to improve the general conditions for using drugs that are well-established in adult medicine for the treatment of children.
 ...
PMID:[Specific features and problems in the pharmacotherapy of schizophrenic psychoses in children and adolescents]. 1247 10

A modified version of the Waldrop scale (WS) was used to assess the prevalence of minor physical anomalies in schizophrenic patients (n = 71) and healthy controls (n = 65). The mean total WS score was 3.32 (SD 1.98) for the schizophrenic patients, significantly higher than that for the controls (2.19, SD 1.18). Minor physical anomalies were compared between two schizophrenic groups, divided on the basis of age at onset, early onset schizophrenia (EOS, onset under age 18 years) group and late onset schizophrenia (LOS, onset at or above age 20 years) group. The mean total WS score was 3.92 (SD 1.86) in the EOS group, significantly higher than the 2.59 (SD 1.79) in the LOS group. Minor physical anomalies are an indirect index for early prenatal central nervous system (CNS) maldevelopment; the present study indicated association between minor physical anomalies and EOS, thus a relationship between early prenatal CNS maldevelopment and EOS. These results support the hypothesis that EOS constitutes a subset of schizophrenia in which neurodevelopmental damage is largely involved.
 ...
PMID:Minor physical anomalies in childhood and adolescent onset schizophrenia. 1251 50

Abnormal neurodevelopment and poor premorbid function have been described in schizophrenia. It is unclear whether abnormalities in these domains are increased in patients with early onset schizophrenia (EOS; onset before the 18th birthday) and whether they act to precipitate the earlier onset of the disorder. To address these questions, we collected information based on maternal interviews about the premorbid function of 40 adolescents with recent onset schizophrenia and an equal number of healthy controls using the Developmental Scale Score, the Premorbid Schizoid and Schizotypal Trait Scale (PSST) and Premorbid Adjustment Scale (PAS). Data on the PSST and PAS were also available in 54 patients with adult onset schizophrenia (AOS; onset after the 20th birthday). Compared to healthy controls, EOS patients had (a). delayed speech milestones, difficulties in reading and spelling and greater overall developmental deviance; (b). poor premorbid adjustment in childhood, which became even more deviant in adolescence particularly in boys and (c). more schizophrenia spectrum traits. Both premorbid adjustment and personality traits were more abnormal in patients with increased developmental deviance suggesting the possibility that they represent different manifestations of ongoing abnormalities in developmental processes. EOS patients had more impaired premorbid adjustment in adolescence and schizophrenia spectrum traits compared to AOS cases. Age of onset was related to developmental deviance, premorbid schizophrenia spectrum traits and childhood adjustment in EOS patients only.
 ...
PMID:Increased developmental deviance and premorbid dysfunction in early onset schizophrenia. 1276 38

According to the literature, schizophrenia begins in men earlier than in women. It has been argued that the gender-bound age difference is due to the protective antidopaminergic effect of estrogens in women. However, the effect of gender on the age of onset may vary between different types of schizophrenias, and can also be modulated by marital status and by age at onset of illness. Comprehensive data were collected on 3306 DSM IIR schizophrenia patients, aged 15-64 years, who had been discharged from psychiatric hospitals in Finland in 1982, 1986 and 1990. The age of onset of illness (AOI) was defined by the age at the first admission (AFA). Male patients were admitted earlier than female patients, and a small second peak in women appeared at the age of 40-44. However, there were no gender differences in AFA within diagnostic subgroups, except in paranoid schizophrenia in which AFA was lower in men than in women even when marital status was taken into account. Within paranoid schizophrenia, this effect of gender was significant only in those of the patients whose AFA was higher than 30 years. It is suggested that there is no gender difference in AOI in early onset schizophrenia. In later onset, paranoid schizophrenia, the illness seems to manifest in women later than in men.
 ...
PMID:Women have later onset than men in schizophrenia--but only in its paranoid form. Results of the DSP project. 1461 21

Clozapine, an atypical antipsychotic, is the most effective medication for treatment-resistant schizophrenia, but its use is limited by the high risk of neutropenia and agranulocytosis. In children, the rate of clozapine-induced neutropenia is even higher than in adults. We report two cases of children 7- and 12-years old diagnosed with very early onset schizophrenia, who developed neutropenia when treated with clozapine. In both cases addition of lithium carbonate elevated the white blood count (WBC) allowing clozapine rechallenge. WBC and total neutrophil count remained stable long-term with coadministration of clozapine (400-425 mg per day) and lithium with the blood level of 0.8-1.1 microg/mL. This report supports the use of adjunct lithium for clozapine-induced neutropenia as a safe and successful strategy in children.
 ...
PMID:Clozapine-induced neutropenia in children: management with lithium carbonate. 1464 24

The aims of the study were to investigate the relationship between Apolipoprotein E (APOE) polymorphism, risk of schizophrenia, treatment response to conventional anti-psychotics, and age of onset in schizophrenia. The sample comprised 94 Finnish patients with a DSM-IV diagnosis of schizophrenia. Forty-three of the patients were good responders to conventional anti-psychotics and 51 were classified as non-responders. The control group consisted of 98 healthy blood donors. The APOE allele frequencies (epsilon 2, epsilon 3, and epsilon 4) were 4.8, 72.3, and 22.9% in patients and 7.1, 75.0, and 17.9 in controls. None of the differences between groups were statistically significant. No association between treatment response and APOE genotype was found. Patients with APOE epsilon 4/epsilon 4 genotype had a markedly lower age of onset compared with rest of the sample (p=0.0015), which remained significant when controlling for gender (p=0.02). There was an increasing linear trend between the number of epsilon 3 alleles (0, 1, or 2) and age of onset in schizophrenia (p=0.08). An inverse trend was found between the number of epsilon 4 alleles and age of onset (p=0.07). No relationship between APOE polymorphism and risk for schizophrenia was found. APOE epsilon 4/epsilon 4 genotype may be associated with early onset schizophrenia. APOE epsilon 3 allele may function protectively in later onset in this disease.
 ...
PMID:Apolipoprotein E polymorphism is associated with age of onset in schizophrenia. 1522 39

Stability of schizophrenia diagnosis from adolescence to adulthood, antecedents of schizophrenia, and differences in developmental and behavioural histories between subjects with early onset schizophrenia (EOS) and with adult onset schizophrenia (AOS) were investigated in 145 adult subjects diagnosed with mental disorders in adolescence and re-diagnosed on the basis of medical records according to DSM-IV.A very high diagnostic stability schizophrenia was demonstrated at the 28-year follow-up. Several factors, including neurological adversities, delayed language development, low IQ, and congenital functional disability, differentiated significantly between schizophrenic subjects and non-schizophrenic subjects. Histories of concussion, physical abuse, parental divorce, and unstable familial context differentiated significantly between EOS and AOS subjects. Our findings support earlier evidence of schizophrenia being a chronic disorder with high diagnostic stability, and confirm the importance of neurological adversities, delayed language development, and low IQ as factors predictive of schizophrenia. Exploration of four case histories of AOS subjects delineates "pre-schizophrenic warning cluster" where combination of neurological adversities, temperamental problems, antisocial behaviour, preference for solitary play, and unstable family system constitute main factors.
 ...
PMID:Stability and prediction of schizophrenia from adolescence to adulthood. 1579 87


<< Previous 1 2 3 4 5 6 Next >>