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Biomedical subjects

D Fekkes

Publications and source records attributed to D Fekkes.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stress and self-injurious behavior; hormonal and serotonergic parameters in mentally retarded subjects.

Self-injurious behavior (SIB) and stereotyped behavior (SB) are major challenges for professionals in the field of mental retardation. From animal experiments it has become obvious that these behavioral disturbances are not purposeless but may emerge secondary to restrictive environment and may serve de-arousing objectives. In mentally retarded subjects, several hypotheses have been formulated concerning the pathogenesis of SIB, particularly about the involvement of serotonin and beta-endorphin, which are supported by beneficial treatment effects of the opiate antagonist naltrexone and serotonin modulating compounds, respectively. The present study was designed to investigate basal levels of stress-hormonal and serotonergic parameters as well as plasma levels of amino-acids and the beta-carboline norharman in a group of 64 mentally retarded subjects with SB and/or SIB. Allocation to three different groups comprising 17 retarded controls, 26 subjects with mainly SIB and 21 subjects with mainly SB, was originally performed using the scores on the factors Irritability, Stereotypic Behaviour and Hyperactivity of the Aberrant Behavioral Checklist. Because of the overlapping nature of the behavioral parameters, subjects were subsequently divided into three maximally contrasting groups, viz. predominantly SIB, predominantly SB and retarded controls, each comprising 11 subjects. With respect to beta-endorphin, no differences were found either between both the original and maximally contrasting groups or in comparison to nonretarded controls. As compared to retarded controls, a tendency to lower values for total cortisol and cortisol binding globulin appeared to be present in the SIB group, whereas in the SB group a tendency toward higher levels of the major serotonin metabolite 5-HIAA was found. In the contrasting SB group, a trend toward decreased total cortisol level was observed as compared to the retarded control group. In addition, significantly lower values for norharman and tryptophan were demonstrated in the total group of mentally retarded subjects as compared to non-retarded controls. The results of the present study, yielding co-existent disturbances in stress-hormonal and monoaminergic mechanisms as well as in the metabolism of norharman, are in line with the hypothesis that mentally retarded subjects are at risk for the development of stress-related behavioral disorders such as SIB and SB.

Adult↗
PubMed1998

Mood correlates with blood serotonin, but not with glucose measures in patients with recurrent suicidal behavior.

Depressive mood and impulsive-aggressive behavior are relevant to suicidal behavior and have been associated with decreased central serotonergic function. Impulsive behavior and aggression have also been related to abnormal glucose metabolism. To investigate these relationships further, blood serotonin (5-HT), blood glucose measures (glycated hemoglobin (HbA1C) and fructosamine) and self-reported depressive symptoms and anger were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R Axis I diagnosis or use of antidepressants were reasons for exclusion. Intra-individual variations in blood 5-HT were inversely correlated with variations in depressive mood, self-depreciation, and anger, and positively with variations in fructosamine. Intra-individual variations of HbA1c or fructosamine were not correlated with mood. Mean blood 5-HT levels per patient were positively correlated with mean scores of depression and self-depreciation. The contrast between the intra-individual and the inter-individual correlations may reflect a difference between short- vs. long-term effects. The results do support an association between serotonergic function and mood, but not between glucose metabolism and mood, in recurrent suicide attempters.

Adolescent↗
PubMed1998

Platelet serotonin, monoamine oxidase activity, and [3H]paroxetine binding related to impulsive suicide attempts and borderline personality disorder.

BACKGROUND: The aim of the present study was to examine the relationship between suicidal behavior and impulsiveness, and more generally borderline personality disorder on the one hand, and platelet indicators of central serotonergic function on the other. METHODS: After a suicide attempt platelet serotonergic measures were obtained from 144 patients with at least one previous attempt. A major DSM-III-R Axis I diagnosis and the use of antidepressants were reasons for exclusion. RESULTS: Platelet monoamine oxidase (MAO) activity was negatively correlated with the personality traits "multi-impulsive behavior" and "disinhibition." In accordance, platelet MAO activity was also lower in patients with less-planned suicide attempts. Platelet serotonin (5-HT) and recidivism were positively correlated with borderline personality disorder, in particular chronic feelings of emptiness. Platelet 5-HT was lower in patients with alcohol abuse. The maximum number of binding sites (Bmax) for paroxetine binding was positively correlated with "sensation seeking." CONCLUSIONS: These findings support the hypothesis that serotonergic involvement in impulsive suicidal behavior is mediated by the relationship between serotonergic function and impulsiveness as personality trait. Other borderline personality traits relevant to recurrent suicidal behavior, in particular chronic feelings of emptiness, appear also related to serotonergic measures.

Adolescent↗
PubMed1998

Does carbohydrate-rich, protein-poor food prevent a deterioration of mood and cognitive performance of stress-prone subjects when subjected to a stressful task?

This study investigates whether in stress-prone subjects, carbohydrate-rich, protein-poor food (CR/PP) prevents a deterioration of mood and performance under uncontrollable laboratory stress conditions. The assumption was that in stress-prone subjects there is a higher risk of serotonin deficiency in the brain and that carbohydrates may prevent a functional shortage of central serotonin during acute stress, due to their potentiating effect on brain tryptophan. Twenty-four subjects with a high stress-proneness (HS) and 24 subjects with a low stress-proneness (LS) participated in an uncontrollable stress situation under both a CR/PP and a protein-rich, carbohydrate-poor (PR/CP) diet condition. The plasma ratio of tryptophan to the other large neutral amino acids (LNAA) (ratio Tryptophan/ summation operatorLNAA) was determined as a measure indicating the dietary effect on brain tryptophan and serotonin levels. Significant increases were found in the ratio tryptophan/ summation operatorLNAA during the CR/PP diet compared with the PR/CP diet. Experimental stress had significant effects on pulse rate, skin conductance, cortisol and mood in all subjects. During the CR/PP diet only the HS subjects did not show the stress-induced rise in depression, decline in vigour and cortisol elevation that they showed after the PR/CP diet. With respect to cognitive performance, significant dietary effects were found on reaction time. It is suggested that CR/PP food in HS subjects may increase personal control, probably under the influence of higher levels of brain tryptophan and serotonin.

Adolescent↗
PubMed1998

Abnormal amino acid metabolism in patients with early stage Alzheimer dementia.

Plasma levels of several amino acids were studied in 14 patients with early stage probable Alzheimer's disease (AD) and 17 age-matched controls. In the AD patients a possible relationship between amino acid levels and behavioural symptomatology was also investigated. We found significantly reduced levels of tryptophan and methionine in plasma samples from the AD patients compared to the control subjects. Moreover, plasma tyrosine/large neutral amino acids (LNAA) ratio and the ratio of plasma taurine and the product of the plasma levels of methionine and serine (TSM-ratio) were significantly increased in the AD patients in comparison with the controls. However, no difference was found in plasma tryptophan/LNAA ratio and in homocysteine levels between both groups. Concerning the behavioural symptomatology no significant correlation was found between the Reisberg Behave AD scale and plasma amino acid levels or ratios. The reported findings suggest that abnormal amino acid metabolism is present in the early stages of AD. We hypothesize that this abnormality could play a role in the pathogenesis of behavioural changes occurring in later stages of AD.

Aged↗
PubMed1998

Serotonergic, catecholaminergic, and cardiovascular reactions to mental stress in female migraine patients. A controlled study.

This study aimed at the combined assessment of the serotonergic and sympathetic nervous system reactions of migraine patients before, during, and after the induction of mental stress in order to detect the possible role of these reactions in inducing a migraine attack. The responses to mental stress of the migraine patients were compared to a group of patients suffering from tension headache and a control group. Activation of the sympathoadrenomedullary system due to mental stress was successfully induced in the migraine patients (n = 23), in the tension headache patients (n = 18), and in the control group (n = 22). The results of this study present evidence of increased cardiovascular activity in migraine patients as compared to nonmigraineurs. However, no evidence was found of a specific serotonergic, sympathoadrenomedullary, or cerebrovascular response of migraine patients to mental stress as compared to nonmigraineurs.

Adolescent↗
PubMed1998

Serotoninergic status in patients with hereditary vascular retinopathy syndrome.

AIM/BACKGROUND: In a new autosomal dominant syndrome (which the authors called hereditary vascular retinopathy (HVR)) cerebral ischaemia, Raynaud's phenomenon, and migraine are the most striking features. As serotonin (5-HT) is known to play a role in vasospastic processes, Raynaud's phenomenon, and migraine they wondered whether the serotoninergic status in patients with HVR is different. Therefore, it was decided to investigate some serotoninergic variables in these patients. METHODS: The study was conducted in 12 patients with HVR, 10 relatives, and 19 healthy controls. The levels of intraplatelet and plasma 5-HT were measured, as well as the plasma levels of its precursor amino acid tryptophan and the ratio of tryptophan to the large neutral amino acids, which compete with the transport of tryptophan through the blood-brain barrier. RESULTS: In both the patients with HVR and in nine relative the concentrations of 5-HT in plasma and platelets were significantly lower than in controls. The plasma levels of tryptophan and the tryptophan ratio were also found to be lower in the patient group compared with the control group, but not in the relatives. CONCLUSION: The observed alterations in 5-HT and its precursor tryptophan strongly suggest the existence of a malfunctioning of the serotoninergic system in the HVR syndrome.

Adult↗
PubMed1997

Platelet serotonin and [3H]paroxetine binding correlate with recurrence of suicidal behavior.

To distinguish state- from trait-dependent associations between serotonergic function and suicidal behavior, platelet serotonergic measures were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R axis I diagnosis or use of antidepressants were reasons for exclusion. A higher affinity constant (KD) of platelet [3H]paroxetine binding was related to a higher risk of short-term recurrence of a suicide attempt, suggesting a state relationship. Higher levels of platelet serotonin at baseline were a significant predictor of a recurrent suicide attempt within the year of follow-up, suggesting a trait relationship. These associations held equally within the subgroup of 73 patients with a borderline personality disorder. Neither the maximum number of binding sites (Bmax) of [3H]paroxetine nor platelet monoamine oxidase activity correlated with suicidality. The observed association between indicators of platelet serotonin uptake and suicidal behavior suggests a state- and trait-dependency between suicidality and central serotonergic dysfunction.

Adolescent↗
PubMed1997

Effects of clomipramine on plasma amino acids and serotonergic parameters in panic disorder and depression.

We examined the effects of long-term (six months) treatment with the serotonin potentiating tricyclic antidepressant clomipramine on several serotonergic parameters in panic disorder and depressive patients. Serotonin (5-HT) levels in blood, platelets and plasma were significantly reduced to 4%, 3% and 28% of their respective baseline values. In addition, the plasma level of tryptophan was also significantly reduced, although the decrease was only 16%. Three months after discontinuation of clomipramine treatment, 5-HT in blood and platelets reached baseline values again, while the plasma 5-HT level was still reduced to 68% of pretreatment values. Unexpectedly, the plasma tryptophan concentration was even lower at this time-point than after six months of treatment. These results show that clomipramine not only has an effect on 5-HT levels in blood, platelets and plasma, but also on plasma tryptophan concentration. We speculate that low plasma tryptophan after treatment may constitute a risk for the recurrence of psychopathology.

Adult↗
PubMed1997

Trait anxiety, coping with stress, and norharman.

Plasma levels of the beta-carboline norharman, concentration of platelet 5-HT, trait measures of anxiety, and measures of coping and defense mechanisms were compared for 15 patients with panic disorder and 24 healthy volunteers. Patients indicated that they made less use of the defense mechanism of principalization than control subjects. No other differences between patients and controls were significant. Platelet 5-HT concentration was positively correlated with the subjectively reported anxiety. Plasma norharman concentration was negatively correlated with the defense mechanisms of principalization and repression and positively correlated with coping strategies involving palliation. The positive correlations of norharman levels with projection and self-comforting fell short of significance and existed in the patient group only. No correlation was apparent between levels of plasma norharman and scores on anxiety. It was concluded that norharman is not a marker for panic disorder or trait anxiety, but that it might reflect intrapsychic and coping processes.

Adaptation, Psychological↗
PubMed1996

State-of-the-art of high-performance liquid chromatographic analysis of amino acids in physiological samples.

Nowadays, the fast and sensitive high-performance liquid chromatographic (HPLC) analysis of derivatized amino acids is a good alternative to the ion-exchange chromatography (IEC) method for plasma amino acids. However, several precautions have to be taken in order to obtain reliable data on the concentration of amino acids in physiological fluids. These include the collection, centrifugation, storage conditions and the method of deproteinization. Furthermore, the method of pre-column derivatization in connection with the protein precipitant used and the choice of the chromatographic system which determines the overall resolution are important factors. HPLC methods using pre-column derivatization with o-phthaldialdehyde were suitable for the accurate determination of many primary amino acids in plasma because of their high sensitivity, simplicity, speed and reliability. When the determination of secondary amino acids and cystine was also necessary, the phenylisothiocyanate method was the preferred technique. The intra-laboratory variability of the HPLC method was satisfactory while the inter-laboratory variation of this method was found to be similar to that of IEC, HPLC methods capable of separating over forty physiological amino acids seem promising for the analysis of urine samples.

Amino Acids↗
PubMed1996

Eicosanoid and amino acid metabolism in transient acute psychoses with psychedelic symptoms.

It has been hypothesized that a disturbance of glutathione (GSH) metabolism might be a common factor in many psychiatric disorders. The aim of the present study was to test this hypothesis in transient acute psychotic patients with distorted perceptions. Since the metabolism of GSH is related to that of thromboxane B2 (TXB2), prostaglandin E (PGE) and some amino acids, we determined these substances in the plasma of 15 patients and 17 normal controls. Plasma concentrations of TXB2 were significantly higher and concentrations of serine and tryptophan were significantly lower in patients than in controls. Large variation was observed in plasma PGE levels in patients, although mean values did not differ significantly from controls. These results are consistent with the hypothesis that the metabolism of GSH is impaired in transient psychotic states.

Adult↗
PubMed1995

Validation of the determination of amino acids in plasma by high-performance liquid chromatography using automated pre-column derivatization with o-phthaldialdehyde.

A sensitive and reproducible fully automated method for the determination of amino acids in plasma based on reversed-phase high-performance liquid chromatography and o-phthaldialdehyde pre-column derivatization is described. A 5-microns Spherisorb ODS 2 column (125 x 3 mm I.D.) was selected for routine determination. Over 40 physiological amino acids could be determined within 49 min (injection to injection) and 48 samples could be processed unattended. The coefficients of variation for most amino acids in plasma were below 4%. We were also able to measure trace amounts of amino acids in plasma normally not detected in a routine analysis. The results obtained with the method described compared favourably with those of conventional amino acid analysis (r = 0.997) and were in excellent agreement with those of other laboratories (r = 0.999).

Adult↗
PubMed1995

Stress, serotonergic function, and mood in users of oral contraceptives.

The relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other large neutral amino acids (LNAAs), mood, and food intake was investigated in women taking monophasic oral contraceptives containing progestagens. Subjects experiencing high levels of stress displayed significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during the pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives.

Adult↗
PubMed1994

The inhibitory effect of norharman on morphine withdrawal syndrome in rats: comparison with ibogaine.

Norharman (20 mg/kg, i.p.) and ibogaine (40 mg/kg, i.p.) significantly attenuated naloxone (4 mg/kg, i.p.)-precipitated withdrawal syndrome in morphine-dependent rats. Several withdrawal signs, such as teeth-chattering, chewing, penile licking and diarrhoea, were decreased by both norharman and ibogaine. In addition, norharman reduced also the withdrawal grooming and rearing. It is concluded that both norharman and ibogaine are inhibitors of withdrawal syndrome in morphine-dependent rats.

Animals↗
PubMed1994

Abnormal plasma levels of serine, methionine, and taurine in transient acute polymorphic psychosis.

The present study explored the usefulness of plasma amino acid concentrations in discriminating a subgroup of patients with transient acute polymorphic psychoses characterized by psychosensory symptoms (APP+ patients). Levels of amino acids in the plasma of APP+ patients were compared with levels in psychiatric patients with other types of psychotic symptomatology and a healthy control group. Both the APP+ patients and patients with bipolar affective disorder had significantly lower plasma concentrations of serine compared with concentrations in the other groups studied. Since the plasma concentrations of taurine and methionine were also different in the APP+ patients, the ratio of taurine to the product of serine and methionine (the TSM ratio) was used in an attempt to increase the sensitivity in discriminating these patients. The TSM ratio in the APP+ patients was significantly higher than those in the other groups studied, except for the patients with bipolar affective disorder. It appears that the determination of serine and the TSM ratio in the plasma of psychotic patients may be a useful diagnostic validator in a group of patients with acute polymorphic psychoses.

Adult↗