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W F Gattaz

Publications and source records attributed to W F Gattaz.

At least 73 records · Page 4Linked to original sources
PubMed1991

Oestradiol enhances the vulnerability threshold for schizophrenia in women by an early effect on dopaminergic neurotransmission. Evidence from an epidemiological study and from animal experiments.

In a representative sample of 392 first hospital admissions for schizophrenia from a population of 1.5 million we assessed the "true" age of onset by a semi-standardized interview "IRAOS". We demonstrated that the mean age at onset of the disease is 3-4 years higher in females than in males, with the lifetime risk being exactly equal. In males, the rates of onset show a steep increase - starting from school age and reaching their maximum value in the age group 15-24 years - followed by a steady decrease. Females reach the first peak with a clear delay between 20 and 29 years. After the decrease, a second smaller peak is observed consistently in females within the age group 45-49 years and over. After having excluded competing explanations, we hypothesized that the effect of oestradiol on the dopaminergic system enhances the vulnerability threshold, which is lowered again during the menopause. Alternatively, we assumed that testosterone reduces the vulnerability threshold and thus furthers the earlier onset of the disease in males. We tested the hypotheses in three animal models by examining the effect of gonadal hormones on haloperidol-induced catalepsy and on apomorphine-induced stereotypies in both neonatal and adult rats. No clear influence by testosterone was shown. Oestradiol caused a significant reduction of both dopamine-agonist and dopamine-antagonist induced behaviour. The effects were stronger in neonatal rats. Since oestradiol caused the dopamine (DA) receptor affinity for sulpiride to be reduced by a factor of 2.8, we assumed that the behavioural changes due to oestradiol were accounted for by a down-regulation of DA receptor sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

An animal model for the effects of estradiol on dopamine-mediated behavior: implications for sex differences in schizophrenia.

Schizophrenic women have been consistently found to have a later age of onset and a less severe clinical course of illness as compared with schizophrenic men. Because these differences are not explained by diagnostic artifacts or sociocultural factors, we tested the hypothesis that they are determined by the influence of the gonadal hormones testosterone and estradiol on dopaminergic (DA) neurotransmission. We used animal models in which the effects of the hormones on behavioral changes induced by the DA antagonist haloperidol (catalepsy) and by the DA agonist apomorphine (oral stereotypies, grooming and sitting behavior) were investigated in neonatal and in adult treated rats. No consistent effects of testosterone were observed. Estradiol significantly reduced the behavioral changes induced by both haloperidol and apomorphine, and this effect was more pronounced in neonatally treated animals. These results suggest a downward regulation of DA neurotransmission by estradiol, which is supported by the results of 3H-sulpiride binding determinations in brain homogenates from the same animals: estradiol caused a 2.8-fold reduction of DA receptor affinity to sulpiride. Our findings suggest that estradiol might act as a protective modulator in schizophrenia by enhancing the vulnerability threshold for psychosis through the downward regulation of DA neurotransmission. Such mechanism could explain, at least in part, the later onset and the more favorable course of schizophrenia in female patients.

Age Factors↗
PubMed1991

Psychiatric aspects of male genital self-mutilation.

From the beginning of the century to this day 57 cases of male genital self-mutilation have been reported in the English literature. In German publications we found 5 case descriptions. Although no precise data are available on the prevalence of male genital self-mutilation, such acts are presumably much more frequent than the small number of published cases would suggest. In the literature several features are regarded as risk factors for self-mutilation, such as e.g. homosexual or transsexual tendencies, repudiation of the male genitals, absence of a competent male for identification during childhood, feeling of guilt for sexual offences, and self-injury in the anamnesis. The most frequent diagnoses are schizophrenia and affective psychosis; alcohol intoxication was diagnosed in about one-fourth of the cases published. In the present paper we summarize data from the literature on epidemiology, psychopathology, psychodynamic and sociocultural factors in male genital automutilation and we describe 2 new cases of self-castration in which several of the risk factors described above were observed. We conclude that although it is difficult to estimate the risk of self-castration in view of the heterogeneity of the respective patient groups, the danger of such deeds should be kept in mind if the above factors are present.

Adult↗
PubMed1990

Increased serum phospholipase A2 activity in schizophrenia: a replication study.

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. Because a disordered phospholipid metabolism has frequently been reported in schizophrenia, we investigated the PLA2 activity in serum from 14 drug-free paranoid schizophrenic patients, 20 healthy controls, and 8 nonschizophrenic psychiatric patients. Schizophrenics showed significantly higher PLA2 activity than healthy controls and nonschizophrenic patients. The increment in schizophrenics was not due to increased concentration of pancreatic secretory PLA2, as concerning pancreatic PLA2 no differences were found among the 3 proband groups. The present findings confirm the results of our previous study and suggest that increased serum PLA2 activity might reflect an increment in the intracellular enzyme activity in schizophrenia. In the brain the activation of intracellular PLA2 results in changes in neuronal activity due to alterations in receptor sensitivity and in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathogenesis of schizophrenia should be investigated in further experiments.

Adult↗
PubMed1990

[Possible involvement of phospholipase A2 in the pathogenesis of schizophrenia].

Phospholipase A2 (PLA2) is a key enzyme in the metabolism of phospholipids. PLA2 is enriched in neuronal membranes and plays an essential role in the functioning of membrane structures in the brain. Because a disordered phospholipid metabolism has been postulated in schizophrenia we started in 1985 a series of exploratory studies in an attempt to clarify the role of PLA2 in schizophrenic disorders. Our results can presently be summed up as follows: 1. Drug-free schizophrenics showed significantly higher PLA2 activity in serum and in plasma as compared with healthy controls as well as with nonschizophrenic psychiatric patients; the latter did not differ from the control group with regard to PLA2 activity. These findings suggest that increased PLA2 activity might be specific for schizophrenia. 2. The possibility that increased PLA2 activity is an artifact due to prior neuroleptic treatment could be ruled out as improbable by the findings that a) neuroleptic treatment significantly reduced PLA2 activity, and b) increased PLA2 activity was also found in first-onset, never-treated schizophrenic patients. 3. Increased PLA2 activity in schizophrenic patients was not caused by the entry of pancreatic enzyme into circulation. Our findings in serum rather suggest that the increment reflects increased intracellular enzyme activity. We speculate that our results might reflect an increment of the intraneuronal PLA2 activity in the brain. The activation of PLA2 in the brain was found to result in changes in neuronal function due to alterations in receptor sensitivity as well as in neurotransmitter metabolism. The possibility that such PLA2-induced mechanisms are involved in the pathology of schizophrenia should be investigated in further experiments.

Adult↗
PubMed1990

Münchhausen syndrome: psychopathology and management.

A case report on a patient with Münchhausen syndrome is presented and the psychopathological features are compared to other reports in the literature. Diagnosis and differential diagnosis are discussed with regard to other somatoform disorders such as conversion disorder and somatization disorder as well as to malingering and cenesthesic schizophrenia. The management of Münchhausen syndrome is aggravated by the low compliance in these patients, who expose themselves to serious complications of unnecessary medical and surgical procedures. Early diagnosis could to a considerable extent exclude these iatrogenic risks. We recommend that patients presenting the psychopathological features of a Münchhausen syndrome should be conservatively observed and an attempt to clarify both the medical and the psychiatric diagnosis should be made before any invasive procedure is undertaken.

Adult↗
PubMed1989

Acute and subchronic effects of low-dose bromocriptine in haloperidol-treated schizophrenics.

The effects of the acute (within 24 hr) and subchronic (21 days) addition of low-dose bromocriptine (2.5 mg/day) were compared to placebo in schizophrenic patients treated concomitantly with haloperidol. After 24 hr patients on bromocriptine (n = 15) showed a mean improvement of 29% in the total score of the Brief Psychiatric Rating Scale (BPRS) as compared to 14% in the placebo group (n = 15) (p less than 0.10). The acute improvement correlated negatively with bromocriptine plasma levels; patients with the highest reduction in BPRS score had the lowest plasma levels (between 50 and 150 pg/ml) at 60, 90, and 120 min after intake. The improvement in the bromocriptine group continued until the 10th day of the trial, when a nonsignificant increase in the total BPRS score took place. Analysis of Variance of the overall BPRS improvement during the 21 days revealed no significant difference between both patient groups. Our results give modest support to the idea of an acute antipsychotic response to low-dose dopamine agonists in neuroleptic-treated patients, but fail to support their clinical usefulness in the subchronic treatment of schizophrenia.

Adult↗
PubMed1989

Neurotensin-like immunoreactivity in cerebrospinal fluid of patients with schizophrenia, depression, anorexia nervosa-bulimia, and premenstrual syndrome.

Neurotensin (NT) concentrations in cerebrospinal fluid (CSF) were measured by a sensitive and specific radioimmunoassay in psychiatric patients and age- and sex-matched normal controls. No increase in CSF NT concentrations was observed after antipsychotic drug treatment. CSF NT concentrations were significantly lower in one group of schizophrenic subjects. NT concentrations were unaltered in patients with depression, anorexia/bulimia, or premenstrual syndrome, and no rostral-caudal gradient for NT in CSF was evident. NT concentrations were not related to age or sex, and probenecid treatment did not alter CSF NT concentrations. Finally CSF NT concentrations were unaltered in paranoid schizophrenic subjects. These findings confirm and extend previous studies of CSF NT that showed certain patients with schizophrenia, nonparanoid type, have reduced CSF concentrations of this tridecapeptide.

Adult↗
PubMed1988

The evaluation of 4-hydroxy-3-methoxyphenylglycol sulfate as a possible marker of central norepinephrine turnover. Studies in healthy volunteers and depressed patients.

Much evidence indicates that urinary 4-hydroxy-3-methoxyphenylethyleneglycol (MHPG) is an insensitive measure of central norepinephrine metabolism. This conclusion, however, seems to apply mainly to total urinary MHPG, since previous findings point to the possibility that the major proportion of urinary MHPG sulfate originates in the CNS, while most urinary MHPG glucuronide originates in peripheral organs. To examine this hypothesis, experiments were performed by which we altered MHPG turnover in man at two different stages: firstly, strong physical exercise (ergometer) increased the urinary excretion rate of MHPG glucuronide and not that of MHPG-sulfate; secondly, ethanol (l g/kg), which is known to block the metabolism of MHPG to vanilmandelic acid in the liver, increases the urinary excretion rate of the glucuronide and not that of sulfate. Both experiments indicate that alteration of peripheral norepinephrine turnover changes the urinary excretion of MHPG glucuronide only and not that of sulfate, thus providing strong, albeit indirect, evidence for a primarily central origin of MHPG sulfate. Preliminary experiments in 32 depressed patients showed little difference in both MHPG fractions compared with healthy controls, apart from a slightly reduced excretion rate of glucuronide. These findings fail to provide any evidence of central, and only small changes in peripheral norepinephrine metabolism in depression.

Adult↗
PubMed1988

CT scans and neuroleptic response in schizophrenia: a multidimensional approach.

Structural brain abnormalities in schizophrenia have been reported in a number of studies using computed tomography (CT). However, the prevalence and the localization of the abnormalities vary widely among studies. These discrepancies might stem from clinical and demographic differences among samples, from the choice of the CT parameters, or from the use of different criteria to define abnormalities. In an attempt to overcome these difficulties, we studied 12 CT parameters in 30 schizophrenic patients and 30 sex- and age-matched controls, and evaluated the data simultaneously through multidimensional scaling (MDS). MDS offers a graphic representation in which subtle deviations in the different CT parameters can be detected, independently of predetermined criteria for the definition of abnormalities. MDS distinguished 13 patients from the controls as having deviant values in one or more CT parameters. Five of these patients were first-onset schizophrenics. Patients with deviant CT parameters showed significantly poorer response to haloperidol therapy over 3 weeks than did patients without deviant CT parameters. Our results suggest that the MDS approach might be useful in identifying more precisely patients with and without structural brain abnormalities.

Adult↗
PubMed1988

[Cerebral computed tomography and schizophrenia: a critical review of the literature].

Structural brain abnormalities in schizophrenia have been reported by several computertomographic (CT) studies. However the prevalence and the localization of the abnormalities vary widely among studies. These differences might stem from samples heterogeneity, from the choice of the CT parameter to be investigated and from the use of different criteria for defining abnormalities. In spite of some contradictory findings, it seems established that at least one subgroup of schizophrenic patients shows mild or moderate brain atrophy; this subgroup might be characterized by a chronic course of the disease, poor response to neuroleptic therapy, and the presence of other neurodiagnostic signs of a diffuse brain dysfunction such as neuropsychological impairment, EEG abnormalities and neurological "soft signs". Atrophic findings have been observed in young schizophrenic patients at the first onset of the disease, indicating that the development of the structural abnormalities are not a consequence of a chronic disease and treatment. Schizophrenics with atrophy are unlikely to have a genetic loading (family history) with schizophrenia and they present more frequently pregnancy and birth complications as well as brain trauma in the first years of development. Because schizophrenics with brain atrophy might represent a more homogeneous subgroup with regard to clinical and aetiopathological variables, it is still an important task to identify more precisely these patients on the basis of CT data and then to study the features that could characterize this subgroup.

Cerebral Ventricles↗
PubMed1987

Increased plasma phospholipase-A2 activity in schizophrenic patients: reduction after neuroleptic therapy.

Phospholipase-A2 (PLA2) is a key enzyme in the metabolism of phospholipids, and it may play an important role in neuronal function and neuronal plasticity. We determined the activity of PLA2 in the plasma of 20 drug-free schizophrenic patients, 6 nonschizophrenic psychiatric patients, and 21 healthy controls. Schizophrenic patients showed significantly higher plasma PLA2 activity than controls, and higher than our nonschizophrenic patients. Seventy percent of the schizophrenics had enzyme activity higher than the highest value from the control group. The increased plasma PLA2 activity in schizophrenics was reduced to the level of the controls after 3 weeks of neuroleptic treatment. These findings warrant further study for possible implications of this increased PLA2 activity in the etiopathology of schizophrenia.

Adult↗
PubMed1986

Cerebrospinal fluid concentrations of free GABA in schizophrenia: no changes after haloperidol treatment.

The concentrations of free GABA were determined in the cerebrospinal fluid of 19 paranoid schizophrenic patients before and after 3 weeks on haloperidol treatment. No significant effect of the neuroleptic treatment on the CSF free GABA concentrations was detected. Furthermore, no correlations were found between changes in GABA concentrations and psychopathological improvement on the Brief Psychiatric Rating Scale. These negative findings are at variance with earlier reports of increased or decreased CSF GABA concentrations after neuroleptics and suggest that subtle changes of the amino acid concentrations in the brain might not be faithfully reflected in the concentrations of its free fraction in the cerebrospinal fluid.

Adult↗