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Biomedical subjects

M Maes

Publications and source records attributed to M Maes.

At least 199 records · Page 11Linked to original sources
PubMed1995

The macrophage-T-lymphocyte theory of schizophrenia: additional evidence.

Chronically activated macrophages and T-lymphocytes, along with excessive interleukin-2 and other cytokine secretions, were previously proposed as the fundamental mediators of schizophrenia. This paper provides further support for the immune model of schizophrenia, including evidence on neurotransmitter abnormalities, the low amplitude of the auditory P300 event-related potential, the neurodevelopmental model of schizophrenia and the possible involvement of the locus ceruleus in schizophrenia.

Acetylcholine↗
PubMed1995

Haloperidol plasma 'threshold' levels for relapse prevention in schizophrenia: a study with haloperidol decanoate.

Forty-eight schizophrenic outpatients treated with flexible doses of haloperidol decanoate were followed up in a naturalistic fashion for 3 years with periodic monitoring of clinical symptoms, side effects and haloperidol plasma concentrations. There was no relationship between plasma level and clinical response, however categorical data analysis showed that patients with plasma levels over 4 ng/ml had a significantly reduced relapse rate compared with patients with plasma levels below this plasma 'threshold' level. This effect could be observed during the first, second as well as third year of treatment. The relapse rate did not change significantly in relation to time (during years 1, 2, 3), when patients with haloperidol plasma levels below and equal to or over 4 ng/ml were considered separately. In patients with haloperidol equal to or over 4 ng/ml, the variability (measured as coefficient of variation %) in the total scores of SAPS and SANS was lower, indicating a better clinical stability. These data are in fairly good agreement with other literature findings showing that an indiscriminate dose reduction strategy during long-term treatment of schizophrenic disorders with haloperidol decanoate should be discouraged, since it leads to an increase in the relapse rate. Before deciding about a dose reduction, clinicians should take into careful consideration some clinically relevant variables (i.e. frequency of previous relapses, severity of symptoms, iatrogenic depression, risk for development of extrapyramidal side effects) for each patient. A better clinical stability during treatment with haloperidol decanoate can be obtained when plasma 'threshold' levels for response are reached.

Adult↗
PubMed1995

Plasma concentrations of excitatory amino acids, serine, glycine, taurine and histidine in major depression.

This study was carried out to investigate plasma levels of excitatory amino acids, such as glutamate and aspartate, and glutamine, serine, glycine, taurine and histidine in major depression. The plasma amino acids were determined by means of HPLC in 22 normal controls and 25 unmedicated patients with major depression. Major depression was characterized by higher plasma taurine levels than normal controls. Significantly lower plasma glycine values and a higher serine/glycine ratio were observed in the depressed group. No significant differences in glutamine, histidine, serine or aspartate levels could be detected between the study groups. By means of linear discriminant analysis, a highly significant separation between major depressed subjects and normal volunteers was found using glycine, glutamate and taurine as discriminatory variables. No significant relationships between any of the amino acids and severity of depression could be found. The results suggest that major depression is accompanied by perturbations in the serine/glycine ratio, excitatory amino acids, such as glutamate, and inhibitory amino acids, such as taurine.

Adult↗
PubMed1995

Increased plasma serine concentrations in depression.

Recently, it has been shown that higher plasma serine concentrations are a possible biological marker for psychoses including schizophrenia. The present study was carried out in order to investigate plasma serine levels in 123 depressed subjects (41 minor; 47 simple major; 35 melancholic depressives) and 50 normal controls. It was found that plasma serine concentrations were significantly higher in depressed subjects than in normal controls. There were no significant correlations between plasma serine and postdexamethasone cortisol values. Dexamethasone administration had a significant suppressive effect on plasma serine levels in depression but not in normal controls. In the latter--but not in depressed subjects--there were significant positive correlations between plasma serine and L-tryptophan concentrations.

Adult↗
PubMed1995

[Growth hormone receptor and binding protein: roles in cellular responsiveness to growth hormone].

In most species, the structure of the growth hormone-binding protein (GH-BP) is identical to that of the growth hormone receptor (GH-R). The affinity (Ka) of the GH-BP is however 10 x lower than that of the receptor. Two mechanisms of production of the GH-BP have been described: in the human and the rabbit, the GH-BP is cleaved near the cellular membrane by proteolysis and shed into the extracellular compartment while in murine species, the serum GH-BP is produced by alternative splicing of the gene coding for the GH receptor. The GH-BP prolongs the 1/2 life of plasma GH, dampening the free GH levels during peaks and maintaining free hormone levels during troughs via the slow dissociation of GH from the complex GH-GHBP. By controlling free GH levels within and between peaks, GH-BP would thus play an important role in modulating GH action at the cellular level. In several physiological and physiopathological conditions, GH-BP and GH-R are coordinately regulated. However, there are situations such as during pregnancy or certain periods of development where these 2 proteins are not co-expressed. Therefore, GH-BP circulating levels do not necessarily represent cellular GH-R concentrations. In the rat, GH-BP and GH-R are regulated by nutritional and endocrine factors, among those are GH, insulin and gonadal steroids. In the human, the mechanism responsible for the increase of the circulating GH-BP during infancy is still unknown. Finally, the eventual role of GH-BP in transmitting the intracellular message of GH following its binding to the receptor is still unknown.

Animals↗
PubMed1994

Seasonal variation in peripheral blood leukocyte subsets and in serum interleukin-6, and soluble interleukin-2 and -6 receptor concentrations in normal volunteers.

This study has been carried out in order to investigate seasonal variation in peripheral blood immune cells, such as leukocytes, monocytes, neutrophils, lymphocytes, CD3+ T, CD4+ T, CD8+ T, CD25+ T, CD20+ B, and serum interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R) and sIL-2R levels in normal volunteers. Toward this end, 26 normal volunteers (13 men, 13 women) had monthly blood samplings during one calendar year for peripheral blood count, flow cytometric enumeration of peripheral leukocyte subsets and immunoassays of IL-6, sIL-6R and sIL-2R. It was found that most of the immune variables change rhythmically during the seasons as a group phenomenon. Statistically significant yearly variations with seasonal rhythms, i.e. annual rhythms or harmonics, such as semiannual, tetramensual and trimensual rhythms, were found in the number of leukocytes, neutrophils, monocytes, lymphocytes, CD4+ T, CD8+ T, CD25+ T, CD20+ B cells, in the CD4+/CD8+ ratio, and serum IL-6 and sIL-6R levels. It is concluded that the immune system is characterized by a multifrequency time-structure with significant high-amplitude yearly variations in the number of some peripheral blood leukocyte subsets.

Antigens, CD↗
PubMed1994

Lower serum prolyl endopeptidase enzyme activity in major depression: further evidence that peptidases play a role in the pathophysiology of depression.

Prolyl endopeptidase (PEP) is a serine proteinase, which may cleave peptides that are involved in the pathophysiology of major depression, such as arginine vasopressin, beta-endorphin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone, and maybe corticotropin-releasing hormone. PEP may be involved in activation of cell-mediated immunity, autoimmune and inflammatory responses, which repeatedly occur in severe depression. The present study investigates serum PEP activity in 33 normal controls, 16 minor, 14 simple major, and 18 melancholic depressed subjects. Pre-dexamethasone and post-dexamethasone (DST) intact adrenocorticotropic hormone (ACTH) and cortisol values were determined in 33 depressed subjects. Serum PEP activity was significantly lower in depressed subjects compared to normal controls and in melancholic depressed subjects compared to minor and simple major depressed subjects. Up to 61.1% of the melancholic patients had serum PEP activities below the mean PEP values of normal controls minus two SDs. In the depressed study group, significant negative correlations between serum PEP activity and severity of illness, post-DST cortisol, and ACTH values were observed. There was a trend toward higher serum PEP activity with increasing age. It is hypothesized that lower serum PEP activity, and lower serum activity of other peptidases, may play a role in the neuroendocrine and immune pathophysiology of major depression.

Adrenocorticotropic Hormone↗
PubMed1994

Effects of buspirone on plasma prolactin and cortisol levels in major depressed and normal subjects.

The cortisol response to ipsapirone (a 5-HT1A-partial agonist that produces a dose-dependent increase in plasma cortisol secretion in man) is blunted in major depression. Buspirone is another 5-HT1A agonist that increases cortisol secretion in man. This study investigated cortisol and prolactin (PRL) responses to buspirone (30 mg orally) in 45 major depressed subjects and 28 normal controls. Buspirone administration yielded a significant increase in cortisol and PRL levels in both normal controls and depressed subjects. No differences in buspirone-induced hormone responses were found either between major depressives and normal controls or between melancholic and nonmelancholic depressives. There were no significant relationships between severity of depression and any of the hormonal responses to buspirone. PRL responses to buspirone were significantly higher in women than in men.

Adult↗
PubMed1994

Parameters influencing SPET regional brain uptake of technetium-99m hexamethylpropylene amine oxine measured by calibrated point sources as an external standard.

Using calibrated point sources as an external standard to convert single-photon emission tomography (SPET) brain counts into absolute values of regional brain uptake (rBU) of technetium-99m hexamethylpropylene amine oxime (HMPAO), the relative contribution of different parameters to interindividual variability of cerebellar rBU was examined in 33 healthy volunteers. Stepwise regression analysis identified body surface as the most important factor underlying interindividual variability (P < 0.001), when compared with brain volume. In the normal volunteer population presented, age decrement of rBU corrected for body surface and brain volume equalled 60.5-0.20 x age. Based on the data of eight normal volunteers, including four test-retest studies with heart rate (HR) differences greater than 5 units and four test-stress studies with doubling of heart rate after bicycle exercise, influence of heart rate may be expressed by the equation delta rBU = 0.35 delta HR. Clinically, estimation of the relative influence of different factors allows normalization and extension of the applicability of the rBU quantification method used from longitudinal studies to group comparisons. Interestingly, results of the Daily Stress Inventory Scale and a subjective rating scale suggest the absence of a significant influence of minor stress on rBU. When using one vial per patient, chromatography may be omitted in clinical routine practice and lipophilicity may be estimated as 90% of the injected dose, if administered within 10 min after preparation. Finally, sensitivity of the quantification method was tested in eight volunteers using acetazolamide brain activation and showed a mean increase in cerebellar rBU of 30.2%, varying between 14.1% and 75.9%.

Acetazolamide↗
PubMed1994

Effect of pindolol on the L-5-HTP-induced increase in plasma prolactin and cortisol concentrations in man.

Previous studies with direct-acting serotonin (5-HT) agonists and antagonists have demonstrated that stimulation of 5-HT1A, 5-HT1C and 5-HT2 receptors may promote cortisol and prolactin (PRL) secretion in man. There is also evidence that 5-HT1C/2 receptor stimulation contributes to the cortisol and PRL responses following administration of the 5-HT precursor, L-5-hydroxytryptophan (L-5-HTP), in man. To clarify the possible contribution of 5-HT1A receptor stimulation to the ability of L-5-HTP to stimulate cortisol and PRL secretion in man, the effect of pindolol, a beta adrenoceptor antagonist that is also a 5-HT1A partial agonist, on the L-5-HTP-induced increases in cortisol and PRL secretion, was examined in 12 normal male volunteers. Pretreatment with pindolol, 30 mg orally, significantly inhibited the PRL but not the cortisol response to L-5-HTP, 200 mg PO. Pindolol alone decreased basal plasma PRL levels and increased basal plasma cortisol levels, possibly due to 5-HT1A antagonist and agonists effects, respectively. These data, coupled with observations from other studies, suggest that the L-5-HTP-induced increase in PRL but not cortisol secretion requires 5-HT1A receptor activation. PRL secretion due to 5-HT formed from exogenous L-5-HTP may require the availability of both intact 5-HT1A and 5-HT2/5-HT1C receptors, since blockade of either receptor type inhibited the PRL response to L-5-HTP. The implication of this synergistic effect for interpretation of neuroendocrine studies involving the serotonergic system in man is discussed.

5-Hydroxytryptophan↗
PubMed1994

Binding of [3H]paroxetine to platelets of depressed patients: seasonal differences and effects of diagnostic classification.

[3H]Paroxetine is a more reliable ligand for studying the serotonin (5-HT) transporter complex than [3H]imipramine. The present study investigates [3H]paroxetine binding to platelets in 54 depressed in-patients (18 minor, 16 simple major and 20 melancholic depressed patients) and 16 healthy controls. There were no significant differences in maximal number of binding sites between depressed subjects and normal controls. There was no correlation between [3H]paroxetine binding to platelet membranes and severity of depression. [3H]Paroxetine binding to platelets was significantly higher in spring than in summer, fall and winter.

Adult↗
PubMed1994

Hypozincemia in depression.

This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.

Adult↗
PubMed1994

Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response.

There is now some evidence that major depression may be accompanied by an immune response. The latter condition is suggested by elevated secretion of neopterin and interferon-gamma (IFN gamma) and by lower L-tryptophan (L-TRP) plasma levels. This study investigated the plasma levels of neopterin, L-TRP, and the L-TRP/competing amino acids (CAA) ratio in 30 normal control subjects and 47 depressed subjects (16 minor depressed, 13 simple major depressed, and 18 melancholic subjects), and IFN gamma secretion by mitogen-stimulated peripheral blood mononuclear cells in 7 normal control subjects and 13 major depressed subjects. Plasma neopterin levels were significantly higher in depressed subjects than in normal controls; 61% of melancholic patients had increased neopterin levels (> or = 7 nmol/l) with a specificity of 90%. Patients with major depression had significantly lower L-TRP and L-TRP/CAA values compared with normal control subjects. The amino acid values were significantly and negatively correlated with plasma neopterin levels. Major depressed subjects exhibited significantly higher IFN gamma secretion than did normal control subjects. The results further support the hypothesis that major depression is accompanied by an immune response and that the lower L-TRP availability in that illness may be an epiphenomenon of immune activation.

Adult↗
PubMed1994

A further investigation of basal HPT axis function in unipolar depression: effects of diagnosis, hospitalization, and dexamethasone administration.

Hypothalamic-pituitary-thyroid (HPT) axis function was assessed in depressed subjects 1 and 8 days after hospital admission, and after the administration of 1 mg of dexamethasone. Plasma levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by ultrasensitive assays in 16 patients with minor depression, 15 patients with simple major depression, and 13 patients with melancholia. The postdexamethasone adrenocorticotropic hormone (ACTH) (intact 1-39 molecule) and cortisol values were determined. Basal TSH values were significantly lower in melancholic patients than in patients with minor and simple major depression on the day after admission and 1 week later. Basal TSH values determined 1 week after admission were significantly and negatively related to FT4 values and severity of depression. There were no significant differences in basal TSH, FT3, and FT4 values obtained on day 1 and day 8 after hospital admission. Dexamethasone administration had a significant suppressant effect on basal TSH and FT3 values. Patients who failed to suppress cortisol after the dexamethasone suppression test (DST) exhibited significantly less suppression of basal TSH values than did DST cortisol suppressors.

Adrenocorticotropic Hormone↗
PubMed1994

Effect of the placebo control condition in neuroendocrine challenge studies.

Neuroendocrine challenge studies are frequently used to make inferences about the pathophysiology of psychiatric illness or about the effects of chronic psychotropic drug treatment on brain monoamine function. The outcome of these exploratory neuroendocrine tests, however, may be influenced by the effects of confounding variables, such as specific stress effects and variations in basal hormone levels. The inclusion of a placebo control condition minimizes the variability due to these variables. A number of recent neuroendocrine studies have omitted the placebo control condition. Based on experimental data, it can be shown that failure to include a placebo control condition may result in both Type I and Type II errors of inference. These results suggest a placebo control condition should be included in exploratory neuroendocrine challenge studies.

5-Hydroxytryptophan↗
PubMed1994

The relevance of the in- versus outpatient status for studies on HPA-axis in depression: spontaneous hypercortisolism is a feature of major depressed inpatients and not of major depression per se.

Increased spontaneous activity of the hypothalamic-pituitary-adrenal (HPA)-axis is frequently reported in major depressed inpatients. The aim of the present study was to determine whether there are differences in spontaneous HPA-axis activity between major depressed inpatients and outpatients. Toward this end, the authors measured basal 9:00 a.m. plasma cortisol and the integrated assessment of plasma morning cortisol secretion over 2 (AUC 120) hours in 48 major depressed inpatients, 17 major depressed outpatients and 73 normal volunteers. Major depressed inpatients exhibit significantly higher plasma cortisol values than healthy controls and major depressed outpatients. The cortisol data from the latter are not significantly different from these of the healthy controls. The cortisol differences between in and outpatients were still present after considering the influences of age, sex, body mass index, severity or endogeneity of illness, unipolar/bipolar subclassification, or specific symptoms such as suicidal thoughts, insomnia, psychomotor disorders, psychoticism, weight loss or anxiety. The results indicate that hypercortisolism as measured by basal morning plasma levels is not a feature of major depression per se, but rather of an interaction between the illness and hospitalization.

Adolescent↗