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Biomedical subjects

D G Kirch

Publications and source records attributed to D G Kirch.

At least 37 records · Page 2Linked to original sources
PubMed1993

Infection and autoimmunity as etiologic factors in schizophrenia: a review and reappraisal.

The focus of schizophrenia research has been turning from studies of structural and functional brain abnormalities to an increasing emphasis on possible etiologic factors. One etiologic hypothesis is that schizophrenia is the result of an infection (especially by a virus) or of an autoimmune reaction (perhaps following an infection) against central nervous system (CNS) tissue. Indirect evidence supporting this hypothesis includes possible geographic variance in the prevalence of schizophrenia, a season-of-birth effect, and observed associations between schizophrenia and prenatal exposure to viral epidemics. Several studies of cell-based and humoral immunity, as well as studies of cytokines, have indicated abnormalities in the immune function of schizophrenia patients, but many of these findings have not been replicated consistently. In addition, most observed alterations in immune function have been modest in degree and nonspecific. Attempts to identify a specific infectious agent or an antibody directed against CNS tissue have not produced a consistently replicable finding. In summary, no research evidence to date irrefutably indicates an infectious or autoimmune etiologic process in schizophrenia. It is probably unreasonable, however, to view schizophrenia as having a single cause. It is much more likely to be a heterogeneous disorder resulting from interactions between multiple factors, including the person's genetic endowment and various environmental influences. Infectious agents or CNS autoantibodies may well be among these environmental variables. A major current emphasis is on studying potential interactions between exposure to an infection or an autoimmune response and key early phases of brain development. A corresponding priority in the research agenda will be the development of animal models of CNS development that might elucidate the pathogenic mechanisms of such an interaction.

Autoimmunity↗
PubMed1993

Serum creatine phosphokinase elevations in patients with tardive dyskinesia.

We describe a case of marked increases in serum creatine phosphokinase (CPK) associated with a dramatic exacerbation of tardive dyskinesia (TD). Chart review of eight additional patients with severe TD revealed three cases with mild CPK elevations. These cases suggest that TD, especially when accompanied by dystonia, may be associated with pathology of striated muscle.

Adolescent↗
PubMed1993

The assessment and clinical implications of haloperidol acute-dose, steady-state, and withdrawal pharmacokinetics.

In order to evaluate comprehensively haloperidol pharmacokinetics under fixed-dose treatment conditions, psychiatric patients were studied after treatment with an acute dose, during maintenance therapy, and after withdrawal from haloperidol following steady-state conditions. After single doses, haloperidol appeared rapidly in serum, achieving peak concentration at a mean of 4.5 hours. The range of observed elimination half-life was broad, between 8.5 and 66.6 hours, with a mean of 19.5 hours. Under conditions of chronic dosing, serial measurements of steady-state serum concentration revealed intrapatient coefficients of variation between 2 and 72%. The mean for all patients was 26.4%. Body clearance decreased nonsignificantly, and elimination half-life increased significantly after chronic dosing compared with kinetic parameters determined after a single dose. The concentration of haloperidol in serum obtained at 8 hours after a single dose correlated most strongly (r = 0.73; p < 0.0001) with steady-state concentration resulting from chronic dosing. A value of 4 ng/ml or lower determined 8 hours after a single oral dose of 0.2 mg/kg identified patients who did not accumulate haloperidol during chronic dosing of 0.4 mg/kg per day above a presumed therapeutic range for haloperidol of 5 to 15 ng/ml. The implications of these data for the clinical use of haloperidol are discussed.

Adult↗
PubMed1992

Search for cytomegalovirus in the postmortem brains of schizophrenic patients using the polymerase chain reaction.

Cytomegalovirus infection has a number of features that suggest a possible association between congenital infection and schizophrenia. Previous studies have investigated anticytomegalovirus antibody titers or attempted directly to identify viral antigens in body fluids or brain tissue from schizophrenic subjects but have been limited by the sensitivity of the available methods. The highly sensitive polymerase chain reaction, a newly developed technique for gene amplification, was used to search for cytomegalovirus in the DNA extracted from postmortem temporal cortex samples of eight schizophrenic subjects, eight nonschizophrenic suicide victims, and eight normal controls. Cytomegalovirus-specific DNA amplification was not detected in any of the samples. The implications of this finding for the viral hypothesis of schizophrenia are discussed.

Adult↗
PubMed1992

Blood-CSF barrier permeability and central nervous system immunoglobulin G in schizophrenia.

The ratio of albumin in cerebrospinal fluid (CSF) to serum may serve as an index of the integrity of the blood-CSF barrier, with increases in this ratio indicating increased permeability. The ratio of immunoglobulin G (IgG) in CSF to serum (divided by the albumin ratio to correct for variance in blood-CSF permeability) represents an index of the endogenous production of IgG in the central nervous system (CNS), with increases reflecting a possible infectious and/or autoimmune process stimulating central IgG synthesis. We analyzed simultaneously collected CSF and serum samples from 46 schizophrenic subjects, 8 of whom were studied both on and off neuroleptic treatment, and samples from 20 normal controls. The data indicated increases in CSF/serum albumin ratios or CSF/serum IgG indices in 22% and 20%, respectively, of the schizophrenic patients. Only 3 patients showed elevations in both indices. Comparison of values on and off neuroleptics indicated no significant effect of neuroleptics on these indices.

Adolescent↗
PubMed1992

Effects of chronic nicotine and haloperidol administration on muscarinic receptor-mediated phosphoinositide turnover in rat brain slices.

Muscarinic receptor-mediated phosphoinositide (PI) turnover in rat brain slices was assessed after chronic administration of nicotine (12 mg/kg/day) or haloperidol decanoate (1.5 mg/kg/day), either alone or in combination, for 6 weeks. Nicotine alone did not significantly alter carbachol-induced inositol monophosphate (IP1) accumulation in the frontal cortex, but did result in a significant increase in the hippocampus, and in a decrease in the striatum. Haloperidol alone attenuated carbachol-stimulated IP1 accumulation in all three brain regions. Chronic treatment with combined nicotine and haloperidol resulted in no significant change in carbachol-sensitive IP1 accumulation in either the frontal cortex or hippocampus but did result in a decrease in the striatum. The results suggest significant cross-talk between cholinergic and dopaminergic systems in affecting PI metabolism.

Animals↗
PubMed1992

First-episode psychosis: Part I. Editors' introduction.

Until recently, there has been a conspicuous lack of studies regarding the earliest phases of psychotic illness, with most research on schizophrenia and related disorders focusing on chronically ill patients. Currently, however, a number of investigators have turned their attention toward this topic, exploring the conceptual issues involved in defining the onset of psychosis, using case registers and population-based samples to do crucial epidemiologic studies on the course of schizophrenia, and developing mechanisms for identifying patients with first-episode psychosis and entering them into active research protocols. The issue of the Schizophrenia Bulletin is devoted to articles representing this full range of conceptual and empirical work on first-episode psychosis. The ultimate goal is for researchers working in this area to develop a network to enhance the sharing of concepts and data, with the eventual possibility of developing combined data bases and collaborative studies.

Female↗
PubMed1992

Research on first-episode psychosis: report on a National Institute of Mental Health Workshop.

The need to focus increased research on patients experiencing their first episode of psychosis was emphasized in A National Plan for Schizophrenia Research. To develop strategies for enhancing research in this area, a National Institute of Mental Health Workshop on First-Episode Psychosis was held in 1991. The topics discussed at that workshop are summarized, with key issues including the following: (1) the need for better operational definitions of onset, end of an episode, and relapse of psychosis; (2) careful consideration of inclusion and exclusion criteria related to age, gender, prior treatment, comorbid substance abuse, and similar issues; (3) the challenge of finding patients never exposed to neuroleptics and the value of entering first-episode patients into standardized treatment protocols; (4) the design of followup studies; (5) strategies to increase the pool of applicants; and (6) approaches for increasing power through data sharing and collaboration between groups.

Age Factors↗
PubMed1992

Search for evidence of herpes simplex virus, type 1, or varicella-zoster virus infection in postmortem brain tissue from schizophrenic patients.

The highly sensitive polymerase chain reaction (PCR) was used to search for herpes simplex virus type 1 (HSV-I) or varicella-zoster virus (VZV) in the DNA extracted from postmortem temporal cortex samples of 8 schizophrenic subjects, 8 nonschizophrenic suicide victims and 8 normal controls. HSV-I or VZV-specific DNA amplification was not detected in any of the samples studied.

Base Sequence↗
PubMed1992

Effect of chronic nicotine treatment and withdrawal on rat striatal D1 and D2 dopamine receptors.

The effects on rat striatal dopamine receptors after chronic nicotine administration (3 and 12 mg kg-1 day-1), and after withdrawal from chronic nicotine (12 mg kg-1 day-1), were studied. After 21 days of continuous minipump infusion, the control (saline) and nicotine-treated rats were killed. The nicotine-withdrawal rats were killed on day 28, 7 days after pump removal. Radioligand studies were performed to determine D1 ([3H]SCH23390) and D2 ([3H]spiperone) striatal dopamine receptor affinity (Kd) and maximum binding (Bmax). Dopamine inhibition of antagonist binding at 3 concentrations and the effect of 0.3 mM GTP on binding affinity were examined. No statistically significant differences between control and nicotine treatment or withdrawal groups were noted in either D1 or D2 receptor Kd or Bmax. Although nicotine has been shown to affect nigrostriatal dopamine release, chronic treatment does not appear to alter overall striatal dopaminergic receptor binding parameters.

Animals↗
PubMed1992

Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia.

Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.

Acute-Phase Proteins↗
PubMed1991

Tardive dyskinesia: neuropsychological, computerized tomographic, and psychiatric symptom findings.

Prior studies have suggested that schizophrenic patients with tardive dyskinesia (TD) have an unusual incidence of cognitive impairment, structural brain abnormalities, and negative symptoms. Twenty-seven schizophrenic patients with TD and an equal number of age-, gender-, and education-matched schizophrenic controls were studied. Each patient received neuropsychological testing, psychiatric symptom ratings, and most had cerebral computed tomography (CT) scans. Patients with TD significantly differed from controls on only 1 of 23, cognitive measures, and the overall group performance profiles were highly similar. No differences were observed on symptom ratings. Patients with TD had significantly smaller ventricular-brain ratios (VBRs) than controls. These data fail to support an association of TD with global measures of "organicity." Abnormal movements may result from specific dysfunction within the more purely motor circuits of the basal ganglia without compromising other neural systems involved in cognitive processing.

Adult↗
PubMed1991

Chronic haloperidol treatment attenuates receptor-mediated phosphoinositide turnover in rat brain slices.

The long-term effects of haloperidol on phosphoinositide turnover in rat brain slices were investigated. Continuous treatment with haloperidol decanoate (21 mg/kg I.M. biweekly for 6 weeks) significantly attenuated carbachol- and norepinephrine (NE)-induced inositol phosphate accumulation in rat frontal cortex and hippocampus. In the striatum, the haloperidol treatment also significantly decreased carbachol-stimulated inositol phosphate level but did not significantly affect NE-sensitive phosphoinositide turnover. These effects were not observed in rats treated with a single dose of haloperidol (1.5 mg/kg). Basel levels of inositol phosphate in these 3 brain regions did not change following continuous or single haloperidol doses.

Animals↗