PubMed Health⌕ Search

Biomedical subjects

N Keks

Publications and source records attributed to N Keks.

At least 19 recordsLinked to original sources
PubMed2005

Competence to give informed consent in acute psychosis is associated with symptoms rather than diagnosis.

To investigate the association between competence to give informed consent to treatment, specific symptomology and diagnostic category, 110 inpatients diagnosed with DSM-IV acute schizophrenia (n = 64), schizoaffective disorder (n = 25) and bipolar affective disorder (n = 21) were interviewed using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T) and the Positive and Negative Syndrome Scale (PANSS). Results indicated no significant difference in competence between the three disorders. Elevated positive, cognitive and excitement PANSS factor scores had lower MacCAT-T scores. Further analyses indicated symptoms that impair cognition; particularly, conceptual disorganisation and poor attention were most consistently related to poor performance on competence tests.

Acute Disease↗
PubMed2001

A change in the density of [(3)H]flumazenil, but not [(3)H]muscimol binding, in Brodmann's Area 9 from subjects with bipolar disorder.

BACKGROUND: This study examines the hypothesis that there are changes in cortical serotonergic, GABAergic and glutamatergic systems in bipolar disorder and schizophrenia. METHODS: In situ radioligand binding and autoradiography were used to measure neurochemical markers in Brodmann's Area (BA) 9 from control subjects and subjects with bipolar disorder or schizophrenia (n=8 per group). RESULTS: Compared to tissue from schizophrenic (mean+/-S.E.M, 385+/-44 fmol/mg ETE) and control (383+/-44 fmol/mg ETE) subjects, there was an increase in the density of [(3)H]flumazenil binding to the benzodiazepine binding site on the GABA(A) receptor in subjects with bipolar disorder (451+/-17 fmol/mg ETE; P<0.05). There was no difference in the density of [(3)H]muscimol binding to the GABA(A) receptor or in the density of the serotonin(1A) receptor, serotonin(2A) receptor, ionotropic glutamate receptors or the serotonin transporter between the three cohorts. There was an age-related decrease in NMDA receptor density in control subjects that was absent in schizophrenia and bipolar disorder. An age-related increase in [(3)H]flumazenil binding in schizophrenia was absent in control and bipolar disorder subjects. LIMITATIONS: This study involved a relatively small number of individuals. CONCLUSIONS: An increase in the gamma2-receptor sub-unit in the GABA(A) receptor has been shown to increase benzodiazepine but not [(3)H]muscimol binding, this is the mismatch in binding we have shown in BA 9 from subjects with bipolar disorder. Thus, a change in the assembly of receptor subunits into GABA(A) receptors may be involved in the neuropathology of bipolar disorder. There may also be differences in age-related changes in cortical receptor density between bipolar disorder and schizophrenia.

Adult↗
PubMed2000

New developments in schizophrenia.

BACKGROUND: Over 2% of the population suffer from schizophrenia and related psychoses. Virtually all sufferers now live in the community, and go to see their general practitioners. OBJECTIVE: To overview recent developments in the presentation and causes of schizophrenia and its treatment with medication and psychosocial intervention. DISCUSSION: The diagnostic boundaries of schizophrenia have become less distinct as aetiological and therapeutic similarities between schizoaffective and affective psychoses have emerged. The importance of specific symptom groups (positive, negative, cognitive, manic, depressed) with respect to brain mechanisms and response to treatment has been recognised. It is now thought that recognition of early phase illness and vigorous treatment aimed at relapse prevention may improve long term prognosis. Availability of new medications has improved outcomes. Patients with schizophrenia living in the community need a range of services best delivered through collaborative care between GPs, community and specialist services.

Antipsychotic Agents↗
PubMed2000

The new antipsychotics. How much better are they?

BACKGROUND: Despite considerable efficacy, conventional antipsychotics cause debilitating extrapyramidal side effects and may worsen 'negative' symptoms of schizophrenia. New atypical antipsychotics (clozapine, risperidone, olanzapine) have become available, and quetiepine is expected shortly; it is TGA approved and is currently available to psychiatrists through a familiarization program. OBJECTIVE: To inform general practitioners about the novel antipsychotics and their therapeutic role in contrast to conventional antipsychotic drugs. DISCUSSION: The major benefit offered by atypical antipsychotics is that these drugs are less likely to cause distressing and disabling extrapyramidal side effects at therapeutically effective doses than conventional drugs. Advantages in terms of efficacy are marginal, though clozapine is superior to conventional drugs in treatment resistant patients. The new drugs are not without other side effects. Clozapine can cause agranulocytosis, needs ongoing haematological monitoring and is only available through specialist centres. However, the new drugs do improve overall outcome. Use of risperidone, olanzapine and quetiepine is now widely recommended in preference to conventional drugs, while clozapine is used when other drugs have failed.

Antipsychotic Agents↗
PubMed1999

No change in the density of the serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex from subjects with schizophrenia.

Changes in serotonin receptors and the serotonin transporter have been reported in the dorsolateral prefrontal cortex from subjects with schizophrenia, an area of the brain thought to be important in the pathology of the illness. To further our understanding on how such changes could play a role in the pathology of the illness, in situ radioligand binding with autoradiography was used to measure the density of the serotonin1A receptor, the serotonin4 receptor and the serotonin transporter in the dorsolateral prefrontal cortex, obtained at autopsy, from 10 schizophrenic and 10 control subjects. The binding of [3H]8-OH-DPAT to serotonin1A receptor, [3H]GR113808 to the 5HT4 receptor and [3H]citalopram to serotonin transporter was not altered in subjects with schizophrenia. significantly, only in tissue from the control subjects was there a relationship between age and the density of the serotonin4 receptor in Brodmann's areas 8 (r = 0.71, P = 0.02) and 10 (r = -0.67, P = 0.03). Importantly, this confounding factor did not influence the comparison of the density of serotonin4 receptor in the tissue from the schizophrenic and control subjects. This study has failed to show a difference in the density of serotonin1A receptor, the serotonin4 receptor or the serotonin transporter in the dorsolateral prefrontal cortex (Brodmann's areas 8, 9 and 10) from subjects with schizophrenia. These data suggest that not all serotonergic markers are altered in the dorsolateral prefrontal cortex from schizophrenic subjects.

Carrier Proteins↗
PubMed1997

The binding of both [3H]nemonapride and [3H]raclopride is increased in schizophrenia.

We performed a postmortem autoradiographic study to compare the density of dopamine D4-like sites in caudate putamen section from age-matched schizophrenia (n = 15) and control (n = 15) populations. The densities of the D4-like sites were estimated by subtracting the density of [3H]raclopride (binding D2 and D3 receptors) from the density of [3H]nemonapride (binding D2, D3, and D4 receptors). The findings revealed that in the schizophrenia population there was a significant increase in the binding of both [3H]nemonapride (2.3-fold) and [3H]raclopride (1.9-fold). In addition, in the schizophrenia population the density of D4-like sites was increased 2.6-fold.

Adult↗
PubMed1997

Cognitive-existential group therapy for patients with primary breast cancer--techniques and themes.

We describe a model of cognitive-existential group therapy designed to be integrated over 6 months with regimens of adjuvant chemotherapy given as conventional medical treatment to breast cancer patients with stage 1 and 2 disease. Our broad therapy goals are for members to develop a supportive network, work through grief over losses, improve problem solving and develop cognitive strategies to maximise coping, enhance a sense of mastery over life and re-evaluate priorities for the future. Specific group themes include death anxiety, fear of recurrence, living with uncertainty, understanding treatment with chemotherapy, radiotherapy and hormone regimens, the collaborative doctor-patient relationship, body and self image, sexuality, relationships with partner, friends and family, surgical reconstruction, life style effects and future goals. Active coping skills are developed through teaching formal problem solving and cognitive restructuring of automatic negative thoughts. Technical aspects of the therapy are discussed.

Adaptation, Psychological↗
PubMed1997

Changes in protein kinase C and adenylate cyclase in the temporal lobe from subjects with schizophrenia.

Changes in G-protein linked neurotransmitter receptors have been reported in a number of regions of the brain of schizophrenic subjects. These changes, if functional, could cause a change in proteins such as protein kinase C (PKC) and adenylate cyclase (AC) which are important components of the G-protein linked second messenger cascades. We therefore used autoradiography to measure the distribution and density of [3H]phorbol ester binding to PKC and [3H]forskolin binding to AC in tissue obtained at autopsy from schizophrenic and non-schizophrenic subjects (Controls). There were significant decreases in the density of PKC in the parahippocampal gyrus (687 +/- 60 vs. 885 +/- 51 fmol/mg TE; mean +/- SEM; p < 0.01) and in AC in the dentate gyrus (75 +/- 4.9 vs. 92 +/- 6.5, p < 0.05) from the schizophrenic subjects. These data could indicate that changes in neurotransmitter receptors in the hippocampus from subjects with schizophrenia could have resulted in a change in their associated second messenger systems.

Adenylyl Cyclases↗
PubMed1996

Neither protein kinase C nor adenylate cyclase are altered in the striatum from subjects with schizophrenia.

Dopamine (DA) D2 receptors which act by modulating second messenger pathways that include protein kinase C (PKC) and adenylate cyclase (AC) have been repeatedly shown to be increased in striatum from subjects with schizophrenia. Therefore it seemed possible that chronic up-regulation of DA-D2 receptors in the schizophrenic brain could result in a change in either of these two proteins. Hence we measured PKC and AC in striatum from 20 schizophrenic subjects and 20 non-schizophrenic subjects by quantitative autoradiography and could show no difference in the density of either PKC (436 +/- 35 vs. 485 +/- 29 fmol/mg tissue equivalents (TE), mean +/- SEM) or AC (77 +/- 9 vs. 80 +/- 7 fmol/mg TE) in the tissue from schizophrenic compared to the non-schizophrenic subjects. Thus, these data do not support the hypothesis that PKC or AC are changed in the schizophrenic brain.

Adenylyl Cyclases↗
PubMed1996

A clinical trial of the effects of estrogen in acutely psychotic women.

This study was a preliminary open clinical trial aimed at exploring the hypothesis that estrogen may provide protection against schizophrenia in women. Eleven women with acute psychotic symptoms, as scored on the BPRS, SAPS and SANS, had 0.02 mg estradiol added to neuroleptic treatment for eight weeks. Their response was compared to seven women with similar symptom severity receiving neuroleptic treatment alone. Both groups had baseline hormonal assays of estrogen, progesterone, LH and FSH and underwent regular psychopathology ratings during the eight weeks. The group receiving the estradiol adjunct showed more rapid improvement in psychotic symptoms compared with the group receiving neuroleptics only. This difference was not sustained for the entirety of the trial. Both groups reached similar levels of recovery by the eighth week. These results suggest that estradiol may have antipsychotic properties and/or act as a catalyst for neuroleptic responsiveness in women with schizophrenia.

Acute Disease↗
PubMed1996

Changes in the serotonin transporter in the hippocampus of subjects with schizophrenia identified using [3H]paroxetine.

[3H]paroxetine binding to membrane from hippocampus, obtained at autopsy, from 24 schizophrenic and 24 non-schizophrenic subjects has been measured. The affinity of [3H]paroxetine binding to hippocampal membrane was decreased in subjects with schizophrenia (Kd = 0.50 +/- 0.04 vs. 0.24 +/- 0.02nM; mean +/- S.E.M. p < 0.001) but was not different in schizophrenic subjects who had or had not committed suicide (Kd = 0.50 +/- 0.07 vs. 0.50 +/- 0.04nM). The density of [3H]paroxetine binding sites did not differ between the schizophrenic and non-schizophrenic subjects. For the schizophrenic subjects, there was no relationship between ante-mortem neuroleptic drug treatment and [3H]paroxetine binding to the hippocampal membrane. Finally, this study has shown that neuroleptic drug treatment of rats does not alter [3H]paroxetine binding to the hippocampal membranes. Thus, it would seem that the changes in the affinity of [3H]paroxetine binding to the hippocampus of schizophrenic subjects are not likely to be due to neuroleptic drug treatment but may be involved in the pathology of the illness.

Adult↗
PubMed1996

Serotonin2 receptors and the serotonin transporter in the schizophrenic brain.

The binding of [3H]paroxetine and [3H]ketanserin to particulate membranes from frontal cortex of subjects who had or did not have schizophrenia was measured as was [3H]paroxetine binding to particulate membranes from the hippocampus and caudate nucleus. There was no change in either the affinity or density of [3H]ketanserin binding to membranes from the frontal cortex of subjects who had schizophrenia. Similarly, there was no difference in the density of [3H]paroxetine binding to membranes from subjects who had or did not have schizophrenia. The affinity of [3H]paroxetine binding in the frontal cortex and putamen did not differ in subjects who had schizophrenia. By contrast, there was a significant decrease in the affinity of [3H]paroxetine binding to the hippocampal membrane from subjects who had schizophrenia (0.40 +/- 0.06 nM vs 0.26 +/- 0.02 nM; p < 0.05). Furthermore, this difference was more apparent in the subjects who had schizophrenia and committed suicide (0.49 +/- 0.09 nM) than it was in those who had schizophrenia but did not commit suicide (0.32 +/- 0.09 nM). As [3H]ketanserin binds to the serotonin2 receptor our data suggest that this receptor is not changed in the Brodmann's area 9 of the frontal cortex. By contrast, [3H]paroxetine binds to the serotonin transporter and therefore our data suggest that the serotonin transporter is altered in the hippocampus of subjects with schizophrenia.

Adolescent↗
PubMed1996

Problem of diagnosis in postmortem brain studies of schizophrenia.

OBJECTIVE: The purpose of this study was to determine 1) the reliability of diagnoses of schizophrenia at coronal autopsy and 2) the degree to which the use of different diagnostic instruments for schizophrenia would affect postmortem brain research. METHOD: Eighty-three subjects, recorded at coronal autopsy as having had schizophrenia, were referred for neurochemistry studies. The diagnoses reported to the state coroner's office were reevaluated by a review of psychiatric case histories by clinicians using semistructured assessment and diagnostic criteria. RESULTS: The application of DSM-III-R, Research Diagnostic Criteria (RDC), ICD-10, Schneiderian, and Feighner criteria to the diagnosis of the 83 subjects revealed that 63.9%, 48.2%, 48,2%, 43.4%, and 42.2%, respectively, met the criteria for schizophrenia. Highest concordance was between the RDC and ICD-10 systems, while lowest concordance was between the RDC and Schneider systems. CONCLUSIONS: These data suggest that unless carefully reviewed, diagnosis may be a major confounding factor in postmortem studies of brain tissue from subjects with schizophrenia.

Adult↗
PubMed1996

The density of muscarinic M1 receptors is decreased in the caudate-putamen of subjects with schizophrenia.

Changes in cholinergic neurons have been implicated in the pathology of schizophrenia. Clozapine, an atypical anti-psychotic drug, has been shown to bind with high affinity to the muscarinic1 (M1) receptor suggesting this receptor could be involved in the therapeutic efficacy of the drug. Because of this we measured the density of M1 receptors in the caudate-putamen, obtained at autopsy, from 19 schizophrenic subjects and 19 non-schizophrenic subjects. The density of M1 receptors was decreased in the caudate-putamen from the schizophrenic subjects (181 +/- 20 vs 287 +/- 10 fmol mg-1 TE; mean +/- s.e.m.; P < 0.001). Furthermore, preliminary studies would not suggest that the change in the density of M1 receptors in the tissue from the schizophrenic subjects had resulted from drug treatment prior to death. These data raise the possibility that changes in muscarinic receptors may be involved in the pathology of schizophrenia.

Adult↗
PubMed1995

[3H]paroxetine binding is altered in the hippocampus but not the frontal cortex or caudate nucleus from subjects with schizophrenia.

[3H]Paroxetine binding to particulate membrane from tissue, obtained at autopsy, from the hippocampus, frontal cortex, and caudate nucleus from subjects who had or had not had schizophrenia was measured. The density of [3H]paroxetine binding to membranes from subjects who had or had not had schizophrenia did not differ. Similarly, the affinity of [3H]paroxetine binding in the frontal cortex and caudate nucleus was not different. By contrast, the affinity of [3H]paroxetine binding to hippocampal membrane from subjects who had schizophrenia was significantly lower than the affinity of binding for the nonschizophrenic subjects (0.40 +/- 0.06 vs. 0.26 +/- 0.02; p < 0.05). As [3H]paroxetine binds to the serotonin transporter, these data suggest that the serotonin transporter is altered in the hippocampus in subjects with schizophrenia.

Adult↗
PubMed1994

The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia.

A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects.

Adolescent↗