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Biomedical subjects

H Agren

Publications and source records attributed to H Agren.

At least 55 records · Page 3Linked to original sources
PubMed1998

Cholecystokinin in CSF from depressed patients: possible relations to severity of depression and suicidal behaviour.

Levels of cholecystokinin (CCK) peptides were measured in the CSF from 105 patients suffering from major depressive disorders admitted to a research psychiatric ward for diagnostic evaluation, by a radioimmunoassay method using two different antibodies. Relations between CCK levels and parameters of depression, anxiety, and suicidal behaviour were investigated. Significant inverse correlations were found between CCK levels and certain depression and anxiety parameters. Patients who had made one or more suicide attempts tended to have higher CSF CCK levels than those who had not. No correlations were found between CSF CCK and 5-HIAA or HVA, or with plasma cortisol.

Adult↗
PubMed1998

Executive deficits in major depression.

Clinically depressed patients and control subjects were examined by means of different tests to assess executive functions (the Wisconsin Card Sorting Test, the Stroop Color Word Test and a test of verbal fluency). The results indicate that the depressed patients were generally slower than the controls, as reflected by longer retrieval times for both words and colours. Furthermore, the depressed patients showed impairment with regard to altering behaviour appropriately in response to feedback. However, there were no depression-related increases in perseverative responses, and the ability to inhibit irrelevant information was unaffected by depression. No relationship was found between specific depressive symptoms or the severity of depression and cognitive performance. The overall pattern of results suggests that depression may affect various executive functions in a differentiated manner.

Analysis of Variance↗
PubMed1998

A randomized, double-blind, placebo-controlled trial of buspirone in combination with an SSRI in patients with treatment-refractory depression.

BACKGROUND: Case reports and open studies have reported beneficial therapeutic effects of adding buspirone to a selective serotonin reuptake inhibitor (SSRI) in the management of treatment-refractory depression. This is the first placebo-controlled study to evaluate the efficacy and safety of this combination. METHOD: One hundred nineteen patients (82 women, 37 men) who fulfilled criteria for a major depressive episode according to DSM-IV and who had failed to respond to a minimum of 4 weeks (mean = 211 days) of treatment with citalopram or paroxetine were randomly assigned to 4 weeks of treatment with an SSRI plus buspirone (N = 58) or an SSRI plus placebo (N = 61). In addition, 97 patients participated in an optional open-label poststudy treatment phase with the SSRI plus buspirone for 2 weeks. The primary outcome measure was the score on the Clinical Global Impressions-Improvement (CGI-I) scale. RESULTS: A total of 50.9% of patients in the buspirone group and 46.7% in the placebo group responded after 4 weeks of treatment. The difference in response rate was not statistically significant. No statistically significant differences were found in the frequency of adverse events. At the follow-up of the open SSRI plus buspirone treatment, 69.4% of patients had responded. CONCLUSION: Adding buspirone to an SSRI is a safe and well-tolerated drug regimen. This study failed to demonstrate any difference in efficacy between buspirone or placebo augmentation of an SSRI. It could be argued, however, that the study was inconclusive due to the unusually high placebo response.

Adult↗
PubMed1996

Serotonin-2 and dopamine-1 binding components of clozapine in frontal cortex and striatum in the human brain visualized by positron emission tomography.

The specific binding of N-methyl-11C-clozapine in the human brain was studied in five healthy volunteers with positron emission tomography (PET). Four of the volunteers were reexamined after treatment with the dopamine D1 and D2 receptor antagonist flupenthixol, and all five volunteers were reexamined after pretreatment with the serotonin2 receptor antagonist ritanserin. The examinations after flupenthixol and ritanserin treatment were performed on different occasions. In the flupenthixol part of the study, two of the subjects were given an oral dose of 1 mg flupenthixol 2-3 h before the posttreatment study with PET. The other two subjects received 0.5 mg orally three times during the 24 h preceding the posttreatment PET study, with the last dose being administered < or = 4 h before the scan. All five ritanserin-treated subjects followed the same dosing regimen. During the 5 days preceding the posttreatment PET study, they were given a 10-mg tablet of ritanserin in the evening. The last dose was administered 2-1/2 hours before the study. Both flupenthixol and ritanserin pretreatment were associated with decreased binding of N-methyl-11C-clozapine in dorsolateral and medial frontal cortical regions. These results support previous findings that clozapine has affinity for both dopamine D1 and serotonin 5-HT2 receptors in the human frontal cortex. No consistent change of binding was observed in striatal regions following flupenthixol or ritanserin pretreatment. The clinical aspects of this feature are discussed, both with respect to efficacy and side effects.

Adult↗
PubMed1996

Novel neuropeptide Y processing in human cerebrospinal fluid from depressed patients.

In vitro processing of neuropeptide Y (NPY) in cerebrospinal fluid (CSF) of patients with depression was monitored by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Single peptide bonds in NPY were cleaved to yield N- or C-terminal fragments. Multiple cleavage to form internal peptides was unimportant. Degradation rates varied between individuals, whereas the product distributions were fairly constant. Other peptides did not evidence such proteolysis. MALDI-TOF MS will facilitate extensive investigations of NPY processing that could provide the basis for clinical assays and illuminate the pathophysiology related to depression.

Adult↗
PubMed1995

Tau protein in cerebrospinal fluid: a biochemical marker for axonal degeneration in Alzheimer disease?

Cerebrospinal fluid (CSF) biochemical markers for Alzheimer disease (AD) would be of great value to improve the clinical diagnostic accuracy of the disorder. As abnormally phosphorylated forms of the microtubule-associated protein tau have been consistently found in the brains of AD patients, and since tau can be detected in CSF, two assays based on several well-defined monoclonal tau antibodies were used to study these proteins in CSF. One assay detects most normal and abnormal forms of tau (CSF-tau), while the other is highly specific for phosphorylated tau (CSF-PHFtau). A marked increase in CSF-PHFtau was found in AD (2230 +/- 930 pg/mL), as compared with controls (640 +/- 230 pg/mL; p < 0.0001), vascular dementia, VAD (1610 +/- 840 pg/mL; p < 0.05), frontal lobe dementia, FLD (1530 +/- 1000 pg/mL; p < 0.05), Parkinson disease, PD (720 +/- 590 pg/mL; p < 0.0001), and patients with major depression (230 +/- 130 pg/mL; p < 0.0001). Parallel results were obtained for CSF-tau. No less than 35/40 (88%) of AD patients had a CSF-PHFtau value higher than the cutoff level of 1140 pg/mL in controls. The present study demonstrates that elevated tau/PHFtau levels are consistently found in CSF of AD patients. However, a considerable overlap is still present with other forms of dementia, both VAD and FLD. CSF-tau and CSF-PHFtau may therefore be useful as a positive biochemical marker, to discriminate AD from normal aging, PD, and depressive pseudodementia. Further studies are needed to clarify the sensitivity and specificity of these assays, including follow-up studies with neuropathological examinations.

Aged↗
PubMed1994

Increased concentration of calcitonin gene-related peptide in cerebrospinal fluid of depressed patients. A possible trait marker of major depressive disorder.

Cerebrospinal fluid (CSF) was collected under controlled conditions from subjects suffering from major depression (n = 63) or schizophrenia (n = 28) and from healthy controls (n = 20). Following Sep-pak extraction, calcitonin gene-related peptide immunoreactivity (CGRP-LI) was determined by radioimmunoassay in sample aliquots. CGRP-LI concentrations in CSF were increased in the depressed patients compared to the schizophrenic and control subjects (P < 0.001). No CGRP-LI differences were found between the latter two groups. CGRP-LI did not correlate to any of the technical (e.g. storage conditions) or patient (demographic, biochemical, or clinical) variables investigated. In view of the CGRP's discrete distribution and specific effects in brain and the above results, we hypothesize that increased CSF CGRP-LI might be a trait marker of major depression. Regardless of the mechanisms (altered synthesis/release/metabolism in brain or changed fate in CSF) leading to elevated CSF CGRP-LI, the identification of a possible disease trait marker should contribute to the early diagnosis of major depression and identification of family members at risk and may help in differential diagnosis in other disorders with affective symptomatology.

Adult↗
PubMed1994

PET studies of presynaptic monoamine metabolism in depressed patients and healthy volunteers.

No deranged presynaptic monoamine metabolism in the brain has been directly demonstrated in mood disorders, in spite of the rich but indirect pharmacological evidence for a decreased efficacy of monoaminergic synaptic transmission in depression, especially as for serotonin. The availability of 11C-labelled 5-hydroxytryptophan (5-HTP) and L-DOPA, the direct precursors in the synthetic pathways to serotonin and dopamine, has allowed positron emission tomographic (PET) studies in 8 healthy volunteers and 6 patients suffering from unipolar depression. Main results indicate (1) decreased uptake of [11C]5-HTP and [11C]L-DOPA over the blood-brain barrier in depression (which is not altered by dietary tryptophan depletion in healthy volunteers), and (2) an increased utilization of [11C]5-HTP (but not [11C]L-DOPA), in the lower region of the medial prefrontal cortex, mainly of the left side. This phenomenon presumably mirrors an increased synthesis of serotonin in this area and might represent a local compensatory increase in a situation of a general serotonergic hypometabolism. Analyses of interactions of both ligands between striatal and prefrontal areas suggest significantly stronger positive correlations in depression than in health, that could be interpreted as a less pronounced autonomy between brain regions in depression.

5-Hydroxytryptophan↗
PubMed1994

Noradrenergic activity and prediction of psychotic relapse following haloperidol withdrawal in schizophrenia.

OBJECTIVE: The purpose of this study was to develop a model based on the authors' previous studies to identify which neuroleptic-treated schizophrenic patients are at risk of early relapse following drug withdrawal. METHOD: Clinical and CSF monoamine-related variables obtained for 50 male haloperidol-treated, schizophrenic patients were used in a logistic regression model to identify those who relapsed (N = 24) within 6 weeks after placebo substitution and those who did not (N = 26). RESULTS: The oral dose of haloperidol, weight, CSF norepinephrine, 3-methoxy-4-hydroxyphenylglycol and chromogranin A-like immunoreactivity, and the anxiety and paranoia subscale ratings of the Brief Psychiatric Rating Scale produced a model that correctly predicted 18 relapsers and 21 nonrelapsers. By including the interactions of paranoia subscale by CSF norepinephrine and anxiety by CSF norepinephrine, the model correctly identified 20 relapsers and 23 nonrelapsers with a sensitivity and specificity of 83% and 88%, respectively. CONCLUSIONS: Increased noradrenergic activity during chronic dopamine blockade may be an episode marker and may predict relapse within 6 weeks following haloperidol withdrawal in schizophrenia. Effective relapse prediction models have important practical implications for the treatment of schizophrenia and the understanding of the psychotic relapse process.

Adult↗
PubMed1993

Clinical investigation of monoamine neurotransmitter interactions.

Monoamine neurotransmitter systems are widely thought to be involved in the pathophysiology of affective disorders and schizophrenia and the mechanism of action of antidepressant and antipsychotic drugs. Previous clinical studies have focused on individual monoamine function in isolation, even though a large number of preclinical studies have demonstrated that monoamine neurotransmitter systems interact with one another. In the present paper, preclinical data on monoamine neurotransmitter interactions are reviewed, and two methods for examining monoamine neurotransmitter system interactions in clinical data are presented. One of the best replicated findings in biological psychiatry is that monoamine metabolites in CSF correlate with one another. The degree of correlation may be in part a measure of the degree of interaction between the parent monoamine neurotransmitter systems. Another approach to studying interactions is the use of HVA/5HIAA and HVA/MHPG ratios as an index of interactions between 5HT-DA and NE-DA. When these methods are applied in schizophrenia, patients are found to have decreased monoamine metabolite correlations compared to normal controls. Metabolite correlations increase significantly after antipsychotic treatment, and the HVA/5HIAA and HVA/MPHG ratios also increase, suggesting that neuroleptics may act in part by strengthening interactions between monoamines. BPRS ratings are negatively correlated with HVA/5HIAA and HVA/MHPG so that patients with higher ratios have fewer symptoms, particularly after treatment. These results provide direct experimental support for hypotheses suggesting that interactions between monoamine neurotransmitters are important in schizophrenia. Some of the effects of the atypical neuroleptic, clozapine, on metabolite correlations and ratios are also discussed.

Animals↗
PubMed1992

Uptake and utilization of [beta-11C]5-hydroxytryptophan in human brain studied by positron emission tomography.

The immediate precursor in the serotonin synthetic route, 5-hydroxytryptophan (5-HTP), labeled with 11C in the beta position, has become available for studies using positron emission tomography (PET) to examine serotonin formation in human brain. Normalized uptake and intracerebral utilization of tracer amounts of [beta-11C]5-HTP were studied twice in six healthy male volunteers, three of them before and after pharmacological pretreatments. The kinetic model defines regional utilization as the relative regional radioactivity accumulation rate. Repeat studies showed good reproducibility. Pretreatments with benserazide, p-chlorophenylalanine (PCPA), and unlabeled 5-HTP all significantly increased uptake of [beta-11C]5-HTP. The utilization rates in both striatal and frontal cortex were higher than those in the surrounding brain, indicating that PET studies using [beta-11C]5-HTP as a ligand quantitate selective processes in the utilization of 5-HTP. We tentatively interpret uptake and utilization as a measure of brain serotonin turnover, the selectivity of which was shown by pharmacological interventions in vivo.

5-Hydroxytryptophan↗