Search PubMed⌕ Search

Biomedical subjects

H Agren

Publications and source records attributed to H Agren.

At least 91 records · Page 5Linked to original sources
PubMed1986

Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF.

The repeatedly observed strong positive correlation between 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) in human cerebrospinal fluid (CSF) prompted an investigation to see if conclusions concerning possible interactions between brain serotonin and dopamine turnover could be reached from human CSF concentrations of these acid metabolites. CSF data from patients with depressive disorders diagnosed according to the RDC from Sweden (n = 140) and from the National Institute of Mental Health (n = 35) were used to test structural hypotheses by two statistical approaches--LISREL analysis and logistic regression. Results from both men and women were unequivocal: 5HIAA "controls" HVA, interpretable as a regulatory action of serotonin turnover on dopamine turnover. In women, only 5HIAA was affected by age, height and body size (higher in elderly, short and stout women); no similar relationships were seen in males. The concept of a serotonergic regulation of dopamine turnover was tested on brain punch analyses of serotonin and dopamine and their metabolites in two sets of dogs in a large number of brain areas. Results confirm a facilatory effect of serotonin on indices of dopamine turnover in many brain regions, especially brain stem and hypothalamus. The animal data validate the data analytic approach in humans.

Adolescent↗
PubMed1986

TRH tests with analyses of TSH, prolactin, and GH responses in subtypes of patients with major depressive disorders.

TRH tests were performed on 131 patients with RDC diagnoses of major depressive disorders to study altered endocrine control mechanisms in subtypes of depression. The TSH response to TRH was measured in all patients. In more than a third of the sample the prolactin (PRL) and growth hormone (GH) responses were also analysed. There were no differences between bipolar, primary unipolar and secondary unipolar patients in means of any endocrine variable. However, the expected positive correlation between baseline TSH and delta TSH was absent in the secondary unipolar group, indicating a dysregulation of pituitary TRH receptor sensitivity in this depressive subtype. Only delta TSH was dependent on depressive state, being lower in currently ill primary unipolar patients only. Patients with melancholic features (endogeneity scores high) had blunted TSH responses. Weight loss was connected with TSH blunting in all depressive subtypes. Among patients with blunted delta TSH (less than 5 mU/l) there was no relationship between degree of weight loss and delta TSH. Further, examination of partial correlation coefficients suggests weight loss of affect delta TSH by virtue of its being part of the melancholic syndrome. A significant correlation between blunted delta TSH and nonsuppression of cortisol in the DST was found only among primary unipolar patients, arguing for some independence of the TRH test and the DST in mirroring disturbed endocrine controls in depression.

Adolescent↗
PubMed1986

Suicide and aggression in schizophrenia. Neurobiologic correlates.

In this study of schizophrenic patients, we were unable to find an association between past history of suicide attempt and levels of CSF amine metabolites, response to DST, and ventricular size by CT scan, neurobiologic variables each of which have been reported to be associated with attempted suicide in some patient groups. Our data, however, demonstrate the marked responsiveness of measures of aggressive behavior to neuroleptic treatment, suggesting a dopaminergic involvement in these behaviors when observed in the presence of overt psychotic symptoms. Some support for an association between decreased CNS serotonin function and aggressive behavior was found in drug-free schizophrenics, although difficulty in separating illness from trait factors is an important confounding variable. The need for clinical interventions required to treat severely disturbed and aggressive behavior in the schizophrenic patients studied could not be predicted by any of the neurobiologic variables.

Aggression↗
PubMed1986

Reduced CSF concentrations of homovanillic acid and homovanillic acid to 5-hydroxyindoleacetic acid ratios in depressed patients: relationship to suicidal behavior and dexamethasone nonsuppression.

Depressed patients who had attempted suicide (N = 19) had significantly lower CSF homovanillic acid (HVA) levels than patients who had not attempted suicide (N = 8) and control subjects (N = 41). Intergroup levels of 5-hydroxyindoleacetic acid (5-HIAA) were not significantly different. The ratio of CSF HVA to CSF 5-HIAA was significantly lower in both patient groups than in control subjects, and patients who had attempted suicide had CSF HVA/5-HIAA ratios that were nearly 50% those of the control subjects. The combinations of nonsuppression on the dexamethasone suppression test and either a low CSF HVA level or a low CSF HVA/5-HIAA ratio were significantly more common among patients who had attempted suicide than among those who had not.

Adult↗
PubMed1986

Automated fluorescent analysis for drug-induced cytotoxicity assays.

The human tumor clonogenic assay has been reported to predict for sensitivity of human tumors to a variety of drugs. However, this assay requires large numbers of viable cells, is time-consuming, and takes at least 2 weeks before results are available. To circumvent these problems, Weisenthal developed a microscope-based dye exclusion assay. Because this method is also time-consuming and subject to observer error, we have developed an automated method of quantitating drug cytotoxicity using a flow cytometric cell sorter (FCM). After incubation of drug-exposed tumor cells, acetaldehyde-fixed duck red blood cells (DRBC) are added. Dead tumor cells and the fixed DRBC are stained by the fluorescent dye propidium iodide, which penetrates dead cell membranes. A two-parameter analysis (cell size as measured by narrow angle light scatter vs propidium iodide fluorescence) enables determination of the live tumor cell:DRBC ratio. There was a strong correlation between the FCM method and manual counting (r = 0.958 for cell lines, r = 0.831 for fresh leukemic cells, P less than 0.0001 in both cases). We conclude that the automatized FCM method gives compatible results to the manual dye exclusion assay and increases efficiency.

Adult↗
PubMed1985

Hallucinations in patients with major depression. Interactions between CSF monoaminergic and endorphinergic indices.

CSF levels of radioreceptorassayed endorphins Fraction I (EndFI, n = 92) and homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) (n = 118) were measured in patients with major depressive disorders according to Research Diagnostic Criteria (18% were psychotic; 11% hallucinated during the peak of the depressive episode). CSF measures (both "raw" variables and ranks) were uni- and multivariately correlated with both dichotomized and scored measures of hallucinations of any type. Hallucinations were statistically strongly associated with higher HVA levels, irrespective of prior medication with neuroleptics, and with the interactive product HVA X EndFI and the interactive ratio HVA/5-HIAA. Results suggest interactions between dopaminergic, serotonergic and endorphinergic neurotransmission being involved in the biochemical substrate of depressive hallucinatory episodes.

Adult↗
PubMed1984

Uncoupler-accelerated efflux of 5-hydroxytryptamine from platelets of healthy subjects and patients with unipolar and bipolar depression.

The efflux of 14C-5-hydroxytryptamine (5HT) from platelets of 25 depressed patients (16 unipolar and 9 bipolar) and 22 control subjects was studied in the presence of carbamyl cyanide m-chlorophenylhydrazone (FCCP), which dissipates H+ gradients. FCCP (0.31 microM), at 10 minutes' incubation time, enhanced the efflux of 14C-5HT to a significantly higher extent from platelets of patients with bipolar depression than from platelets of control subjects. An analysis of variance revealed a significant interaction between the diagnostic categories (unipolar, bipolar, and control) and sex in accounting for variation of the FCCP-evoked efflux. The diagnostic category X sex effect was also significant. The results reported indicate that the FCCP-evoked efflux of 5HT is an easily measured biochemical parameter of possible diagnostic interest.

Adult↗
PubMed1984

Low levels of somatostatin in human CSF mark depressive episodes.

Somatostatin-like immunoreactivity was measured in the cerebrospinal fluid (CSF) of 85 inpatients with current or recent episodes of major depressive disorders, diagnosed according to Research Diagnostic Criteria (RDC) as assessed with the Schedule for Affective Disorders and Schizophrenia (SADS). Several biopsychiatric tests were run during the same week of investigation. Results indicate low levels of CSF somatostatin to be a state marker for episodes of depression characterized by sad appearance, feelings of tiredness, insomnia, and subjective inability to acknowledge any external precipitants for the depression. CSF somatostatin was negatively related to platelet monoamine oxidase (MAO) activity; MAO activity appeared to account better for the degree of melancholic features than did somatostatin. The ratio between 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in CSF also correlated negatively with somatostatin. A positive relationship was noted between CSF xanthine and somatostatin. There was a highly significant curvilinear correlation between CSF somatostatin and serum TSH concentrations, but no correlations between CSF somatostatin and serum GH or prolactin, or with plasma cortisol before or after dexamethasone.

Blood Platelets↗
PubMed1984

Brain energy metabolism and blood-brain barrier permeability in depressive patients: analyses of creatine, creatinine, urate, and albumin in CSF and blood.

A reliable method is described using high pressure liquid chromatography to measure creatine, creatinine, and urate in human cerebrospinal fluid (CSF) and blood; albumin was analyzed by routine methods. Creatine and creatinine serve as indices of one aspect of brain energy metabolism, the creatine-creatine phosphate (CrP) shuttle. CSF levels have been adjusted to a set blood level by analysis of covariance. The ratios between CSF and blood concentrations of urate and albumin are two sensitive indices of impaired blood-brain barrier (BBB) function. Analyses were performed on 41 male and 58 female inpatients with RDC major depressive disorders, with a mean age of about 40 years. The CSF creatinine and creatine levels were highly positively age-dependent; this factor as well as possible influences of body habits were removed by way of analysis of covariance from all measures in focus. We describe positive, highly significant correlations between creatinine and monoamine metabolites (HVA and 5HIAA) and purine metabolites (hypoxanthine and xanthine) in CSF, and a strong negative correlation between both BBB permeability measures and the noradrenalin CSF metabolite MHPG. CSF creatinine was negatively linked with suicidal ideation and increased appetite. The BBB tended to be the more permeable the less melancholic the depression. No measure appeared to be dependent on depressive state. Comparisons of depressive subgroups revealed a higher CSF creatinine concentration in sporadic unipolar patients according to Winokur. A particularly wide variance in the albumin ratio was found in pure unipolars. Pure unipolars with an impaired BBB had a more protracted onset, were more suicidal, had a higher erythrocyte sedimentation rate, and lower plasma cortisol levels than those without. Impaired BBB was further linked with a slower EEG rhythm and higher systolic blood pressure. Results suggest significant contributions of brain energy metabolism and deranged BBB permeability in accounting for some aspects of neuronal transmission and modulation as well as the symptomatology of depressive illness.

Adult↗
PubMed1983

Brain purinergic activity linked with depressive symptomatology: hypoxanthine and xanthine in CSF of patients with major depressive disorders.

The purine metabolites hypoxanthine and xanthine were analyzed in cerebrospinal fluid (CSF) of 70 patients with major depressive disorders (diagnosed according to Research Diagnostic Criteria) and, for reference, in 26 nonpsychiatric individuals. In the patient group, levels adjusted by analysis of covariance to same sex, age, height, and weight were univariately and multivariately correlated with both depressive subdiagnoses and individual depressive symptoms. Results indicate that raw CSF levels in depressed patients are significantly correlated with the four variables used in adjustment (for hypoxanthine mainly negatively with height; for xanthine mainly positively with age). Hypoxanthine and xanthine both appear to be linked with the expression of depressive symptomatology: lower levels of hypoxanthine are associated with anger and suicidal tendencies, and higher levels are related to memory disturbance; lower xanthine levels characterize patients with subjective feelings of depression, and in patients with higher levels appetite is poor.

Adult↗
PubMed1983

Depression and CSF endorphin fraction I: seasonal variation and higher levels in unipolar than bipolar patients.

Radioreceptor assay of endorphin Fraction I in the cerebrospinal fluid (CSF) of 92 inpatients suffering from major depression revealed the following: (1) clearly elevated levels as compared to normal control subjects, (2) higher level in unipolar than in bipolar patients, and (3) seasonal rhythms showing peaks in early fall for unipolar patients and late fall for bipolar patients. The annual pattern observed bears some resemblance to the known seasonal variations in the incidence of affective disorders and suicide.

Adult↗
PubMed1983

Nomifensine and amitriptyline in the treatment of depression. A multi-centre double-blind comparison.

Nomifensine, an antidepressive agent acting like a dopamine agonist, was investigated in a randomized double-blind comparison with amitriptyline in 29 patients fulfilling the RDC criteria for major depression. The dosage was 150 mg daily in both treatment groups. Assessments were made at weekly intervals for 6 weeks with the Comprehensive Psychopathological Rating Scale. No significant difference could be demonstrated between the two drugs in overall therapeutic efficiency, and only one item, Fatiguability, differed significantly in favour of amitriptyline. Physical and laboratory variables showed no statistically significant differences. Neither drug elicited serious unwanted effects.

Adult↗
PubMed1983

Purine and monoamine metabolites in cerebrospinal fluid: parallel purinergic and monoaminergic activation in depressive illness?

In the cerebrospinal fluid of 38 patients with major depressive disorders the purine metabolites hypoxanthine and xanthine were positively correlated to the monoamine metabolites HVA and 5HIAA (p less than 0.0001). Hypoxanthine was also positively linked to the noradrenaline metabolite MHPG (p less than 0.005). By the use of multiple regression analysis 70% of the variance in hypoxanthine and 51% of the variance in xanthine were explained by HVA and 5HIAA. The scored magnitude of memory disturbance during depression was positively correlated to hypoxanthine, xanthine, HVA, and 5HIAA, while the degree of somatic anxiety as well as worrying was or tended to be negatively correlated to the same biochemical markers. The conspicuous relationship observed between purine and monoamine metabolite concentrations in CSF during depressive illness might indicate a parallel purinergic and monoaminergic activation of the brain. The observation that certain isolated depressive symptoms appear to relate to hypoxanthine/xanthine in CSF is consistent with the hypothesis of a central role of purines in behaviour.

Adult↗
PubMed1983

Estimation of fetal maturity by amniotic fluid cytology, creatinine, lecithin/sphingomyelin ratio and phosphatidylglycerol.

The value of four amniotic fluid tests--the lecithin/sphingomyelin ratio, the presence of phosphatidylglycerol, amniotic fluid cytology and the creatinine concentration--in the prediction of fetal lung maturity was investigated. The sensitivity was high for all tests except for amniotic fluid cytology, which had a higher specificity. The overall outcome, particularly the value for predicting immaturity, was improved by various combinations of tests. The combination of amniotic fluid cytology and creatinine proved useful in predicting the gestational age. A diagram for estimation of gestational age is presented.

Amniotic Fluid↗
PubMed1983

Depression and somatosensory evoked potentials: II. Correlations between SEP and depressive phenomenology.

In 32 patients with major depressive disorders according to Research Diagnostic Criteria (RDC), symptomatology was rated using the Schedule for Affective Disorders and Schizophrenia (SADS), and somatosensory evoked potentials (SEP) elicited by tactile fingertip stimuli were recorded at the vertex of the scalp. Patients were drug-free except for benzodiazepines. Amplitudes and amplitude/stimulus intensity slopes were adjusted to same sex, age, height, and weight. Uni-and multivariate correlations revealed associations between the N140-P200 amplitude and hypothyroidlike aspects of depression with symptoms such as poor appetite and indecisiveness, and between the P100-N140 slope and intrapunitive aspects of depression with symptoms such as negative self-evaluation and suicidal attempts. Neither attention level nor benzodiazepine medication were reflected in these relationships.

Adult↗