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)

The SADS-LA, a modification of the Lifetime Version of the Schedule for Affective Disorders and Schizophrenia, was designed specifically for studies requiring detailed lifetime information on anxiety disorders, symptoms and traits. This article focuses on current difficulties in assessing and conceptualizing anxiety disorders, as addressed in the SADS-LA. The following topics are discussed: conceptual differentiation of certain anxiety disorders; sub-threshold symptoms and syndromes; the relationship between affective and anxiety syndromes; the residual category, Generalized Anxiety Disorder. We emphasize a lifetime sequential approach to diagnostic assessment for a comprehensive understanding of the interrelationships between mental disorders.
 ...
PMID:Schedule for Affective Disorders and Schizophrenia--Lifetime Version modified for the study of anxiety disorders (SADS-LA): rationale and conceptual development. 380 26

Five groups of subjects underwent EEG sleep recordings, arecoline rapid eye movement (REM) induction response testing, and Schedule for Affective Disorders and Schizophrenia (SADS) interview. Group I: 20 patients with primary major depressive disorder (MDD) (endogenous) without any coexisting anxiety disorder; Group II: 19 primary MDD (endogenous) patients with secondary panic, GAD, or phobic disorders; Group III: 18 patients with primary anxiety disorder without coexisting MDD; Group IV: 14 patients with primary anxiety plus secondary MDD; Group V: 26 normal controls. Modified Research Diagnostic Criteria (RDC) were used for diagnosis, based on the SADS interview. There was considerable overlap of SADS scaled scores between patient groups, which is consistent with a heterogeneous clinical presentation of depressive and anxiety states. REM latency was significantly shorter in patients with primary MDD (without anxiety) as compared with that in patients with primary anxiety (no MDD) and normals. Arecoline REM induction response time was significantly shorter in both primary affective groups (I and II) as compared with primary anxiety (no MDD) patients and normal controls. REM latency and arecoline REM induction time was not significantly different between the primary anxiety groups (III and IV) and normals. The study highlights the use of biological markers in differentiating between clinical syndromes confounded by mixed or overlapping phenomenology.
 ...
PMID:Cholinergic REM induction response: separation of anxiety and depression. 397 73

This is an overview of a two-phase epidemiological study of mental disorders among young adults in a ten-year birth cohort (1949-58) conducted in Israel. A sample of 4914 Israel-born offspring of Jewish immigrants was obtained by full probability sampling procedures and screened for caseness using psychometric symptom scales from the Psychiatric Epidemiology Research Interview (PERI). Those screened positive and almost a fifth of the negatives (N = 2741) were interviewed by psychiatrists using the Schedule for Affective Disorders and Schizophrenia, Israel version (SADS-I), in order to determine prevalence rates of specific disorders as defined by the Research Diagnostic Criteria (RDC). The completion rates for each interview phase were 94.5% and 90.7% respectively. Six-month prevalence rates are presented by gender, ethnic origin, and education. Approximately one-fifth of the birth cohort met current RDC criteria for a disorder at the definite level, excluding the RDC category of 'other psychiatric disorder'. Generalized anxiety disorder and major depressive disorder were the most commonly found types. The striking findings centre on alcoholism and drug use disorder which were exceedingly rare, and the unusually similar rates of major depression for males and females. The results from this study are discussed in comparison with those obtained from other epidemiological studies.
 ...
PMID:An epidemiological study of mental disorders in a 10-year cohort of young adults in Israel. 823 76

A series of 82 children and adolescents with moderate and severe persistent asthma was studied. Their psychopathological problems were compared to those of 82 healthy subjects, matched for age, sex and socio-economic status. The patients completed the Child Depression Inventory, an inventory of fears and anxiety (ECAP) and the Coopersmith Self Esteem Inventory. Parents of asthmatic children filled in the Child Behavior Check List to assess their social competence. The patients were examined with the revised Kiddie Schedule for Affective Disorders and Schizophrenia. There were more anxiety symptoms in the asthmatic group than in the control group. Asthmatics were not significantly more depressed than controls and their self-esteem was as good. We found 29 anxiety disorders, four affective disorders and four disruptive behavior disorders. Generalized anxiety disorder was the main diagnosis (n=24). The asthmatic subgroup presenting anxiety and affective disorders had poorer self esteem, fewer activities and worse social competence than other asthmatics and controls. Adolescents did not seem to have more emotional disturbances than younger patients. Girls did not have more DSM IV anxiety or affective disorders than boys.
 ...
PMID:Prevalence of DSM IV anxiety and affective disorders in a pediatric population of asthmatic children and adolescents. 1080 31

Abnormalities in amygdala and hippocampus have been shown to coexist in schizophrenia (SZ). In the hippocampus, compelling evidence suggests that a disruption of GABA neurotransmission is present mainly in sectors CA4, CA3, and CA2. The amygdala sends important inputs to the hippocampus and is also believed to have a defective GABA system in schizophrenia. To explore the possibility that changes in the hippocampal GABAergic system could be related to an increased inflow of activity originating in the amygdala, a "partial" animal model has been developed. In awake, freely moving, rats a GABA(A) receptor antagonist was infused locally into the basolateral nuclear complex of the amygdala (BLn). Within 2 hours, a decreased density of both the 65- and 67-kDa isoforms of glutamate decarboxylase (GAD(65) and GAD(67)) -immunoreactive (IR) terminals was detected on neuron somata in sectors CA3 and CA2, but not in CA1, CA3, or dentate gyrus. An increase of GAD(67)-IR somata was also found in the dentate gyrus and CA4. In anterograde tracer studies, amygdalo-hippocampal projection fibers were exclusively found in CA3 and CA2, but not CA1. Taken together, these results indicate that activation of amygdalo-hippocampal afferents is associated with the induction of significant changes in the GABA system of the hippocampus, with a subregional distribution that is remarkably similar to that found in SZ. Under pathologic conditions, an excessive discharge of excitatory activity emanating from the amygdala could be capable of altering inhibitory modulation along the trisynaptic pathway. This mechanism may potentially contribute to disturbances of GABAergic function in the major psychoses. Such "partial" rodent modelling provides an important strategy for deciphering the effect of altered cortico-limbic circuits in SZ.
 ...
PMID:Amygdalar activation alters the hippocampal GABA system: "partial" modelling for postmortem changes in schizophrenia. 1116 95

Recent postmortem studies have been suggesting that a defect of GABAergic neurotransmission might occur in the corticolimbic system of subjects with schizophrenia and bipolar disorder. To explore this possibility, a method for immunolocalizing the 65 kdalton isoform of glutamate decarboxylase (GAD(65)) has been developed and applied to the anterior cingulate (ACCx) and prefrontal (PFCx) cortices of 12 normal controls (CONs), 12 schizophrenics (SZs) and 5 manic depressive (MDs) subjects. A computer-assisted technique was employed under strictly blind conditions to determine the density of GAD(65)-IR terminals in apposition with pyramidal (PNs) and nonpyramidal (NPs) neurons and in neuropil (NPL) of layers II, III, V and VI of each cortical region. For SZs, no difference in the numerical density of GAD(65)-IR terminals in contact with either PNs or NPs or in NPL of layers II-VI in ACCx or PFCx was detected. There were also no differences in the size of either PNs and NPs that could have influenced the nature of these findings. Using a pixel count analysis, the size of IR terminals was, however, found to be increased in layers II (10.3%) and III (15.8%) of SZs, but only in subjects treated with neuroleptic drugs. For MDs, the density of GAD(65)-IR terminals was significantly reduced in all four layers of ACCx, but these differences were most significant in layers II (27.8%) and III (37.2%), whether or not the subjected were treated with neuroleptics. In PFCx, the MDs showed similar differences in terminal density for PNs and NPs but not neuropil in the four laminae examined. The MD group showed no differences in either the size of cell bodies or IR terminals. Age and PMI did not account for any of the differences between the CONs vs SZs and MDs. Overall, the results of this study, though preliminary, suggest that there may be complex changes in GABAergic terminals in SZ and MD, ones that may vary with respect to primary diagnosis and neuroleptic exposure.
 ...
PMID:Glutamate decarboxylase(65)-immunoreactive terminals in cingulate and prefrontal cortices of schizophrenic and bipolar brain. 1120 24

In schizophrenia, critical deficits in cognitive functions appear to reflect altered neural processing in the prefrontal cortex (PFC). Given the essential role of inhibitory neurotransmission in mediating these cognitive functions, we sought to determine whether abnormalities in the inhibitory circuitry of the PFC may contribute to the cognitive deficits of schizophrenia. In situ hybridization analyses in postmortem brain tissue from subjects with schizophrenia revealed that a subset of GABA neurons in PFC layers 1-5 do not express detectable levels of the mRNAs encoding glutamate decarboxylase (GAD(67)), a synthesizing enzyme for GABA, or the GABA membrane transporter (GAT-1), which is responsible for the reuptake of GABA into the nerve terminal. Furthermore, the affected GABA neurons appear to include chandelier cells, since decreased expression of GAT-1 mRNA is associated with decreased GAT-1 protein immunoreactivity in chandelier neuron axon terminals. Finally, immunocytochemical studies revealed that decreased GAT-1 immunoreactivity in chandelier neuron axon terminals is associated with an increase in a marker of GABA(A) receptors at the postsynaptic targets of chandelier neuron axons, the axon initial segment (AIS) of pyramidal neurons. These findings suggest that schizophrenia is associated with an up-regulation of GABA(A) receptors at pyramidal neuron AIS in response to deficient GABAergic input from chandelier neurons. Selective disruptions in inhibitory neurotransmission are likely to distort aspects of pyramidal neuron function important for working memory tasks, and thus may contribute to cognitive dysfunction in schizophrenia.
 ...
PMID:Impaired prefrontal inhibition in schizophrenia: relevance for cognitive dysfunction. 1252 90

Decreases in the 67 kDa isoenzyme of brain glutamic acid decarboxylase (GAD(67)) expression have been consistently found in patients with bipolar disorder and schizophrenia. In animals GAD(67) expression is diminished by chronic, but not acute stimulation of dopamine D(2) receptors and by short-term blockade of NMDA receptors. In contrast, chronic treatment with D(2) receptor antagonists enhances GAD(67) expression. Thus, antipsychotic treatment cannot explain the reduction in GAD(67) levels in patients with psychotic disorders. Rather, pathophysiological findings such as reduced viability of cortical glutamatergic neurones (in schizophrenia) or enhanced dopamine sensitivity (in bipolar disorder) might explain the observed reduction in GAD(67). Since reduction in GAD(67) expression leads to reduced levels of GABA, the GABAergic inhibitory control over glutamatergic cells is reduced. Psychosis could result from AMPA receptor activation caused by overactivity of the glutamatergic system. GAD(67) levels would thus be a surrogate marker for psychosis liability. Pharmacological principles that raise GAD(67) expression levels could represent novel targets for antipsychotic therapy.
 ...
PMID:GAD(67): the link between the GABA-deficit hypothesis and the dopaminergic- and glutamatergic theories of psychosis. 1281 40

Recent postmortem studies in humans suggest that defects in GABAergic neurotransmission might contribute to the neuropathology associated with schizophrenia. Disturbances in GABAergic systems may also contribute to the sensorimotor gating deficits classically observed in schizophrenic patients, including deficits in prepulse inhibition (PPI). To explore the relationship, the current study examined the integrity of PPI and startle habituation in knockout (KO) mice that lack the GABA synthesizing enzyme glutamic acid decarboxylase 65 (GAD 65). GAD65 KO mice displayed normal baseline and habituated startle responses, which did not differ from GAD65 wild-type (WT) or heterozygous (HET) mice. However, GAD65 KO mice showed robust deficits in PPI which were reversed by the atypical antipsychotic agent clozapine. These results lend support to the view that abnormalities in GABAergic systems might contribute to the basic pathophysiological mechanisms in schizophrenia.
 ...
PMID:Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment. 1511 43

The polygenic nature of complex psychiatric disorders suggests a common pathway that may be involved in the down-regulation of multiple genes through an epigenetic mechanism. To investigate the role of methylation in down-regulating the expression of mRNAs that may be associated with the schizophrenia phenotype, we have adopted a cell-culture model amenable to this line of investigation. We have administered methionine (2 mM) to primary cultures of cortical neurons prepared from embryonic day 16 mice and show that this treatment down-regulated reelin and glutamic acid decarboxylase 67 (GAD67) mRNA expression but not that corresponding to neuron-specific enolase mRNA. Moreover, methionine increased methylation of the reelin promoter, suggesting a possible mechanism for the observed change. These cultures contain a mixed population of neurons and glia. Approximately 83% of the neurons are GABAergic based on GAD immunoreactivity, and these neurons coexpress high levels of reelin and DNA methyltransferase (Dnmt) 1 immunoreactivity. To examine whether Dnmt1 regulates reelin gene expression, we used an antisense approach to reduce (knock down) Dnmt1 expression. The reduced Dnmt1 mRNA and protein were accompanied by increased reelin mRNA expression. More importantly, the Dnmt1 knockdown blocked the methionine-induced reelin and GAD67 mRNA down-regulation. These data support the hypothesis that the reduced amounts of reelin and GAD67 mRNAs documented in postmortem schizophrenia brain may be the consequence of a Dnmt1-mediated hypermethylation of the corresponding promoters.
 ...
PMID:DNA methyltransferase 1 regulates reelin mRNA expression in mouse primary cortical cultures. 1567 Nov 76


1 2 3 4 5 6 Next >>